For patients with HER2-negative metastatic breast cancer, first line chemotherapy with cabazitaxel (Jevtana) every 3 weeks offers efficacy comparable to that of once-weekly paclitaxel, but with lower risk for peripheral neuropathy and better patient-reported quality of life, investigators in the multicenter CONCERT trial found.

In an open-label clinical trial of 158 patients from 14 hospitals in the United Kingdom, there was no difference in the primary endpoint of progression-free survival (PFS) or a secondary overall survival endpoint between patients randomly assigned to initial chemotherapy with cabazitaxel every 3 weeks or weekly paclitaxel, reported Amit Bahl, MD, of University Hospital Bristol, England, and colleagues.

“Cabazitaxel is safe and well tolerated for metastatic breast cancer and requires fewer hospital visits than weekly paclitaxel, which is very important for patients and health care providers, but more so in the current situation,” he said in an oral abstract session at the American Society of Clinical Oncology annual meeting (Abstract 1008).

Cabazitaxel is currently approved in the United States and Europe in combination with prednisone for treatment of patients with metastatic castration-resistant prostate cancer previously treated with a docetaxel-containing treatment regimen. It is not currently approved for the treatment of metastatic breast cancer, but has been explored for this indication in clinical trials.

“In the metastatic setting, where patients continue on treatment pretty much indefinitely until disease progression or unacceptable toxicity, the use of an every-3-week regimen could be attractive, because it means less visits for the patients, and it appears that this drug has lower toxicity in terms of peripheral neuropathy,” said breast cancer specialist Aditya Bardia, MD, MPH, who was not involved in the study.

Dr. Bardia, of Mass General Cancer Center in Boston, commented on the study in an interview.

Although paclitaxel is commonly used as first-line chemotherapy for HER2-negative metastatic breast cancer, it is associated with only modest response rates, ranging from 21.5% to 53.7% and carries significant risk of peripheral neuropathy, Dr. Bahl and colleagues noted.

“There is an unmet need for an alternative first-line cytotoxic chemotherapy agent, and cabazitaxel is a taxoid agent which has showed promising results in phase 2 trial of metastatic breast cancer patients in the second-line setting, even those with taxane resistance,” he said.
 

Open-label trial

To see whether cabazitaxel could meet those requirements, the investigators conducted a phase 2 randomized trial in which patients with HER2-negative metastatic breast cancer not previously treated with cytotoxic chemotherapy were assigned, 79 in each arm, to receive cabazitaxel 25 mg/m² every 3 weeks, or paclitaxel 80 mg/m² weekly.

The median patient age was 56 years in the cabazitaxel group and 61 years in the paclitaxel group. Roughly two-thirds of patients in each arm had Eastern Cooperative Oncology Group performance status 0, and the remainder had ECOG performance status 1.

In each arm, the median time on treatment was 15 weeks, but treatment delays and dose reductions were more common among patients on paclitaxel than cabazitaxel (61% vs. 39%, and 37% vs. 24%, respectively).

There were 149 PFS events at the time of the analysis. The median PFS with cabazitaxel was 6.7 months vs. 5.8 months with paclitaxel. This difference was not statistically significant. Median overall survival was 20.6 months in the cabazitaxel arm, vs. 18.2 months 20.0 months, respectively.

Similarly, there were no significant differences in either the overall response rates (42% vs. 37%), or time to response.

There were no complete responses with cabazitaxel vs. two (2.5%) with paclitaxel. The respective partial response rates were 41.8% vs. 34.2%.

In a subgroup analysis of PFS, there were no significant between-arm differences, except for an improved PFS in patients 65 and older with cabazitaxel (hazard ratio 0.45, 95% confidence interval, 0.25-0.80).
 

Quality of life favors cabazitaxel

Grade 3 or greater adverse events occurred in 42% of patients on cabazitaxel vs. 51% on paclitaxel. Diarrhea, febrile neutropenia, and nausea were the most common grade 3 or greater events in the cabazitaxel arm, whereas grade 3 or greater lung infection and peripheral neuropathy were more common with paclitaxel.

Sensory peripheral neuropathy of any grade occurred in 16% of patients assigned to cabazitaxel, compared with 54% assigned to paclitaxel. The respective rates of alopecia were 27% and 42%.

Over the course of treatment, the mean EuroQuol EQ-5D-5L single index utility score and visual analogue scale score were higher with cabazitaxel arm compared to paclitaxel, suggesting better patient quality of life with cabazitaxel.

In addition, throughout treatment patients in the cabazitaxel arm reported significantly better scores on The Functional Assessment of Cancer Therapy – Breast (FACT-B) breast cancer subscale, Dr. Bahl said.
 

Second-line may be better

ASCO invited discussant Marleen Kok, MD, PhD, from the Netherlands Cancer Institute in Amsterdam, pointed out that in the phase 2 GENEVIEVE trial comparing the efficacy and safety of cabazitaxel versus weekly paclitaxel as neoadjuvant treatment in patients with triple negative or luminal B/HER2 normal breast cancer the pathologic complete response rate with cabazitaxel was 1.2%, compared with 11% with paclitaxel.

“This GENEVIEVE trial, together with the CONCERT trial, suggests that there is not a big role for cabazitaxel to be used upfront before other taxanes,” she said.

However, in a phase 2 study of cabazitaxel as second-line therapy in patients with HER2-negative metastatic breast cancer who had previously been treated with taxanes, the overall response rate was 23%, “which is still of interest and importance for our patients,” she added.

Dr. Kok did not address quality of life differences between the regimens, however.

In a side note, Dr. Bardia said that “if there were an oral form of paclitaxel, that would certainly be very welcome, in that an oral drug is more convenient for patients, and would require fewer visits to the hospital.”

The CONCERT trial was funded by an investigator-sponsored study grant from Sanofi. Dr. Bahl disclosed honoraria and institutional research funding from Sanofi/Aventis and others, and travel expenses from Bayer and Roche. Dr. Kok disclosed a consulting or advisory role for Bristol Myers Squibb/Medarex, and institutional research funding from that company and others. Dr. Bardia disclosed a consulting or advisory role and research funding to his institution from multiple companies.

For patients with HER2-negative metastatic breast cancer, first line chemotherapy with cabazitaxel (Jevtana) every 3 weeks offers efficacy comparable to that of once-weekly paclitaxel, but with lower risk for peripheral neuropathy and better patient-reported quality of life, investigators in the multicenter CONCERT trial found.

In an open-label clinical trial of 158 patients from 14 hospitals in the United Kingdom, there was no difference in the primary endpoint of progression-free survival (PFS) or a secondary overall survival endpoint between patients randomly assigned to initial chemotherapy with cabazitaxel every 3 weeks or weekly paclitaxel, reported Amit Bahl, MD, of University Hospital Bristol, England, and colleagues.

“Cabazitaxel is safe and well tolerated for metastatic breast cancer and requires fewer hospital visits than weekly paclitaxel, which is very important for patients and health care providers, but more so in the current situation,” he said in an oral abstract session at the American Society of Clinical Oncology annual meeting (Abstract 1008).

Cabazitaxel is currently approved in the United States and Europe in combination with prednisone for treatment of patients with metastatic castration-resistant prostate cancer previously treated with a docetaxel-containing treatment regimen. It is not currently approved for the treatment of metastatic breast cancer, but has been explored for this indication in clinical trials.

“In the metastatic setting, where patients continue on treatment pretty much indefinitely until disease progression or unacceptable toxicity, the use of an every-3-week regimen could be attractive, because it means less visits for the patients, and it appears that this drug has lower toxicity in terms of peripheral neuropathy,” said breast cancer specialist Aditya Bardia, MD, MPH, who was not involved in the study.

Dr. Bardia, of Mass General Cancer Center in Boston, commented on the study in an interview.

Although paclitaxel is commonly used as first-line chemotherapy for HER2-negative metastatic breast cancer, it is associated with only modest response rates, ranging from 21.5% to 53.7% and carries significant risk of peripheral neuropathy, Dr. Bahl and colleagues noted.

“There is an unmet need for an alternative first-line cytotoxic chemotherapy agent, and cabazitaxel is a taxoid agent which has showed promising results in phase 2 trial of metastatic breast cancer patients in the second-line setting, even those with taxane resistance,” he said.
 

Open-label trial

To see whether cabazitaxel could meet those requirements, the investigators conducted a phase 2 randomized trial in which patients with HER2-negative metastatic breast cancer not previously treated with cytotoxic chemotherapy were assigned, 79 in each arm, to receive cabazitaxel 25 mg/m² every 3 weeks, or paclitaxel 80 mg/m² weekly.

The median patient age was 56 years in the cabazitaxel group and 61 years in the paclitaxel group. Roughly two-thirds of patients in each arm had Eastern Cooperative Oncology Group performance status 0, and the remainder had ECOG performance status 1.

In each arm, the median time on treatment was 15 weeks, but treatment delays and dose reductions were more common among patients on paclitaxel than cabazitaxel (61% vs. 39%, and 37% vs. 24%, respectively).

There were 149 PFS events at the time of the analysis. The median PFS with cabazitaxel was 6.7 months vs. 5.8 months with paclitaxel. This difference was not statistically significant. Median overall survival was 20.6 months in the cabazitaxel arm, vs. 18.2 months 20.0 months, respectively.

Similarly, there were no significant differences in either the overall response rates (42% vs. 37%), or time to response.

There were no complete responses with cabazitaxel vs. two (2.5%) with paclitaxel. The respective partial response rates were 41.8% vs. 34.2%.

In a subgroup analysis of PFS, there were no significant between-arm differences, except for an improved PFS in patients 65 and older with cabazitaxel (hazard ratio 0.45, 95% confidence interval, 0.25-0.80).
 

Quality of life favors cabazitaxel

Grade 3 or greater adverse events occurred in 42% of patients on cabazitaxel vs. 51% on paclitaxel. Diarrhea, febrile neutropenia, and nausea were the most common grade 3 or greater events in the cabazitaxel arm, whereas grade 3 or greater lung infection and peripheral neuropathy were more common with paclitaxel.

Sensory peripheral neuropathy of any grade occurred in 16% of patients assigned to cabazitaxel, compared with 54% assigned to paclitaxel. The respective rates of alopecia were 27% and 42%.

Over the course of treatment, the mean EuroQuol EQ-5D-5L single index utility score and visual analogue scale score were higher with cabazitaxel arm compared to paclitaxel, suggesting better patient quality of life with cabazitaxel.

In addition, throughout treatment patients in the cabazitaxel arm reported significantly better scores on The Functional Assessment of Cancer Therapy – Breast (FACT-B) breast cancer subscale, Dr. Bahl said.
 

Second-line may be better

ASCO invited discussant Marleen Kok, MD, PhD, from the Netherlands Cancer Institute in Amsterdam, pointed out that in the phase 2 GENEVIEVE trial comparing the efficacy and safety of cabazitaxel versus weekly paclitaxel as neoadjuvant treatment in patients with triple negative or luminal B/HER2 normal breast cancer the pathologic complete response rate with cabazitaxel was 1.2%, compared with 11% with paclitaxel.

“This GENEVIEVE trial, together with the CONCERT trial, suggests that there is not a big role for cabazitaxel to be used upfront before other taxanes,” she said.

However, in a phase 2 study of cabazitaxel as second-line therapy in patients with HER2-negative metastatic breast cancer who had previously been treated with taxanes, the overall response rate was 23%, “which is still of interest and importance for our patients,” she added.

Dr. Kok did not address quality of life differences between the regimens, however.

In a side note, Dr. Bardia said that “if there were an oral form of paclitaxel, that would certainly be very welcome, in that an oral drug is more convenient for patients, and would require fewer visits to the hospital.”

The CONCERT trial was funded by an investigator-sponsored study grant from Sanofi. Dr. Bahl disclosed honoraria and institutional research funding from Sanofi/Aventis and others, and travel expenses from Bayer and Roche. Dr. Kok disclosed a consulting or advisory role for Bristol Myers Squibb/Medarex, and institutional research funding from that company and others. Dr. Bardia disclosed a consulting or advisory role and research funding to his institution from multiple companies.

For patients with HER2-negative metastatic breast cancer, first line chemotherapy with cabazitaxel (Jevtana) every 3 weeks offers efficacy comparable to that of once-weekly paclitaxel, but with lower risk for peripheral neuropathy and better patient-reported quality of life, investigators in the multicenter CONCERT trial found.

In an open-label clinical trial of 158 patients from 14 hospitals in the United Kingdom, there was no difference in the primary endpoint of progression-free survival (PFS) or a secondary overall survival endpoint between patients randomly assigned to initial chemotherapy with cabazitaxel every 3 weeks or weekly paclitaxel, reported Amit Bahl, MD, of University Hospital Bristol, England, and colleagues.

“Cabazitaxel is safe and well tolerated for metastatic breast cancer and requires fewer hospital visits than weekly paclitaxel, which is very important for patients and health care providers, but more so in the current situation,” he said in an oral abstract session at the American Society of Clinical Oncology annual meeting (Abstract 1008).

Cabazitaxel is currently approved in the United States and Europe in combination with prednisone for treatment of patients with metastatic castration-resistant prostate cancer previously treated with a docetaxel-containing treatment regimen. It is not currently approved for the treatment of metastatic breast cancer, but has been explored for this indication in clinical trials.

“In the metastatic setting, where patients continue on treatment pretty much indefinitely until disease progression or unacceptable toxicity, the use of an every-3-week regimen could be attractive, because it means less visits for the patients, and it appears that this drug has lower toxicity in terms of peripheral neuropathy,” said breast cancer specialist Aditya Bardia, MD, MPH, who was not involved in the study.

Dr. Bardia, of Mass General Cancer Center in Boston, commented on the study in an interview.

Although paclitaxel is commonly used as first-line chemotherapy for HER2-negative metastatic breast cancer, it is associated with only modest response rates, ranging from 21.5% to 53.7% and carries significant risk of peripheral neuropathy, Dr. Bahl and colleagues noted.

“There is an unmet need for an alternative first-line cytotoxic chemotherapy agent, and cabazitaxel is a taxoid agent which has showed promising results in phase 2 trial of metastatic breast cancer patients in the second-line setting, even those with taxane resistance,” he said.
 

Open-label trial

To see whether cabazitaxel could meet those requirements, the investigators conducted a phase 2 randomized trial in which patients with HER2-negative metastatic breast cancer not previously treated with cytotoxic chemotherapy were assigned, 79 in each arm, to receive cabazitaxel 25 mg/m² every 3 weeks, or paclitaxel 80 mg/m² weekly.

The median patient age was 56 years in the cabazitaxel group and 61 years in the paclitaxel group. Roughly two-thirds of patients in each arm had Eastern Cooperative Oncology Group performance status 0, and the remainder had ECOG performance status 1.

In each arm, the median time on treatment was 15 weeks, but treatment delays and dose reductions were more common among patients on paclitaxel than cabazitaxel (61% vs. 39%, and 37% vs. 24%, respectively).

There were 149 PFS events at the time of the analysis. The median PFS with cabazitaxel was 6.7 months vs. 5.8 months with paclitaxel. This difference was not statistically significant. Median overall survival was 20.6 months in the cabazitaxel arm, vs. 18.2 months 20.0 months, respectively.

Similarly, there were no significant differences in either the overall response rates (42% vs. 37%), or time to response.

There were no complete responses with cabazitaxel vs. two (2.5%) with paclitaxel. The respective partial response rates were 41.8% vs. 34.2%.

In a subgroup analysis of PFS, there were no significant between-arm differences, except for an improved PFS in patients 65 and older with cabazitaxel (hazard ratio 0.45, 95% confidence interval, 0.25-0.80).
 

Quality of life favors cabazitaxel

Grade 3 or greater adverse events occurred in 42% of patients on cabazitaxel vs. 51% on paclitaxel. Diarrhea, febrile neutropenia, and nausea were the most common grade 3 or greater events in the cabazitaxel arm, whereas grade 3 or greater lung infection and peripheral neuropathy were more common with paclitaxel.

Sensory peripheral neuropathy of any grade occurred in 16% of patients assigned to cabazitaxel, compared with 54% assigned to paclitaxel. The respective rates of alopecia were 27% and 42%.

Over the course of treatment, the mean EuroQuol EQ-5D-5L single index utility score and visual analogue scale score were higher with cabazitaxel arm compared to paclitaxel, suggesting better patient quality of life with cabazitaxel.

In addition, throughout treatment patients in the cabazitaxel arm reported significantly better scores on The Functional Assessment of Cancer Therapy – Breast (FACT-B) breast cancer subscale, Dr. Bahl said.
 

Second-line may be better

ASCO invited discussant Marleen Kok, MD, PhD, from the Netherlands Cancer Institute in Amsterdam, pointed out that in the phase 2 GENEVIEVE trial comparing the efficacy and safety of cabazitaxel versus weekly paclitaxel as neoadjuvant treatment in patients with triple negative or luminal B/HER2 normal breast cancer the pathologic complete response rate with cabazitaxel was 1.2%, compared with 11% with paclitaxel.

“This GENEVIEVE trial, together with the CONCERT trial, suggests that there is not a big role for cabazitaxel to be used upfront before other taxanes,” she said.

However, in a phase 2 study of cabazitaxel as second-line therapy in patients with HER2-negative metastatic breast cancer who had previously been treated with taxanes, the overall response rate was 23%, “which is still of interest and importance for our patients,” she added.

Dr. Kok did not address quality of life differences between the regimens, however.

In a side note, Dr. Bardia said that “if there were an oral form of paclitaxel, that would certainly be very welcome, in that an oral drug is more convenient for patients, and would require fewer visits to the hospital.”

The CONCERT trial was funded by an investigator-sponsored study grant from Sanofi. Dr. Bahl disclosed honoraria and institutional research funding from Sanofi/Aventis and others, and travel expenses from Bayer and Roche. Dr. Kok disclosed a consulting or advisory role for Bristol Myers Squibb/Medarex, and institutional research funding from that company and others. Dr. Bardia disclosed a consulting or advisory role and research funding to his institution from multiple companies.

The concept of home ownership has changed for this generation, not only in the logistics of the best way to do it, but also in the desire and demand for owning versus renting. According to the Penn Institute for Urban Research, the U.S. homeownership rate is now at 63.7%, the lowest in 48 years. “Homeownership rates have declined for all demographic age groups. Since 2006, the number of households who own their home in the United States has decreased by 674,000 while the number of renters has increased by over 8 million.”¹

But isn’t owning your own home the American dream? Isn’t it a great investment? If we’re looking strictly at the monthly payment numbers, traditionally paying a mortgage is cheaper than paying rent for the same-size home. That became even more true as home prices dropped in 2007-2008 and as interest rates also dropped over the last several years. Then there’s the age-old concept of “building equity” or “throwing away money on rent.” As a financial planner, I get asked all the time about a home as an investment. It certainly can be, like any investment, if you buy and sell at the right time. But something is only an investment if it grows, and you can’t predict if you’re going to buy and sell your house at the right time. The median price of an existing home sold in March 2021 was $329,100. That’s a 17.2% increase from March 2020. Times are certainly crazy right now in the real estate market.

What many people don’t think about are the other costs, and not just financial costs. Today’s generation is more aware of the added stress and burden of maintaining a home and the money you can sink into it for maintenance, let alone remodeling. Then of course there’s the mortgage interest, property taxes, and insurance that you won’t have with a rental. Lastly, the biggest reason today’s generation is choosing to rent more and more is the flexibility. They want to be more mobile, able to get up and move without having to worry about listing, selling, and possibly owing more than the house is worth, and being stuck. We saw this with many residents that bought a home during residency and then tried to sell when they landed their first job, only to find out they owed more than it was worth because of the real estate market collapse of 2008. Approximately 50% of physicians will leave their first job within 1-3 years, so it’s a gamble that you’ll be able to sell your house when you want to for the price you need.

But what are the benefits of buying? First, there is the age-old argument of building equity. If you stay in your house long enough, and plan to sell it when you retire and downsize, it can definitely be an investment. If you keep a mortgage long enough, eventually you’ll pay it off, and have no payment. Mortgage interest is also tax-deductible. Lastly, there are the intangibles – like being able to put down roots, build a community, and have the ability to remodel and customize your home, a feature not usually available when renting.

Now that I’ve effectively talked you out and back in again, what’s the best way to go about buying a house in today’s crazy market? We’ve seen houses list and sell within a day and get multiple offers well over asking price. It’s a very difficult time to buy, but there are ways to make it easier. First, be clear on what you want in a house, especially location. There’s nothing worse than buyer’s remorse in your primary residence, and that happens more these days when people have to quickly make a decision. Find a good, fee-based financial planner to help you decide how much house fits in your budget and your long-term goals. You’d be surprised how easily we can talk ourselves into paying much more than we had originally decided. Use your financial planner to help avoid emotions getting involved and creeping up your price (especially when multiple offers are involved). A good rule of thumb is for a housing payment to be no more than 33% of your take-home income. This includes principal, interest, and taxes. Or, many planners will use the “2x income” rule of thumb. So if you make $300,000, don’t go over $600,000. Although with today’s low interest rates, there is some more wiggle room on that. Next, get a good referral from someone you trust in looking for a realtor. Real estate is a commission-based job and can have some potential conflicts of interest, so getting a recommendation can help. Or, there are realtors who will work for a flat fee, regardless of how much you pay for a house. That can help reduce the conflict.

You made the offer, you beat out the other bids, and you’re getting a house! How are you paying for it? Hopefully, you already got preapproved. This means finding a good, reputable mortgage professional. Get referrals, shop around, and take your time. Get multiple quotes before you start the underwriting process. They shouldn’t have to pull your credit to give you a fairly accurate estimate of what interest rate you’ll qualify for. Usually, they will give you fixed and variable interest quotes. I normally recommend fixed interest. Because interest rates are so low right now, they’re only going to go up in the future, and if you have a variable rate loan, your payment will go up as interest rates rise.

Is a physician loan a good idea? Depending on your circumstance, it can often be a good deal. Most new attendings don’t have cash saved up for a down payment, and these often don’t require one. And the other big benefit is that they won’t consider your student loan payments when calculating your debt-to-income ratio. Mortgage lenders will look at how much other debt you have when determining an approval. And a conventional mortgage will take your student loan payments into consideration, which means you’ll qualify for a much lower payment and purchase price. In my experience, you want a credit score of around 700 or higher to qualify for these types of loans. The only downside of a physician mortgage is the rates are slightly higher. I encourage you to start the application process early; they’re taking upward of 90 days lately.

As the mortgage is being processed, you’ll have an inspection and appraisal, and as long as those are all favorable, you’re in! Now, should you take any surplus income each month and pay extra on your mortgage to pay it down sooner, or invest it? Everyone’s situation is different, but a good rule of thumb is to look at interest rates on the debt you want to pay off versus expected rate of return on the potential investment. For example, if you have extra money, should you invest it in an SP500 index fund that historically gets 8%-12% per year, or put it on the principal of your mortgage that has an interest rate of 3%? Assuming no other factors or goals, and you just want the best bang for your buck, my money would go toward the investment getting 8%-12% over saving 3% on my mortgage.

Take your time, do your research, and find good professionals. There’s no right answer for everyone, but there are certainly some good practices when walking through the first home decision. Here at FinancialMD, we only work with physicians, and we’re happy to chat if you want some guidance on this. Send me an email and subscribe to our weekly Didactic Minute videos on YouTube for more financial tips for young physicians. Good luck!

Mr. Solitro is a financial planner and CEO of FinancialMD. He has no other conflicts of interest.

Investment advisory services offered through FinancialMD, a registered investment adviser. Registration as an investment adviser does not imply a certain level of skill or training. This article is provided for informational purposes only and nothing contained herein should be construed as a solicitation to buy or sell any products. Advisory services are offered only to clients and prospective clients in places where FinancialMD and its investment adviser representatives are registered or exempt from registration. Investing involves the risk of loss of principal. Past performance is no guarantee of future performance and no investment strategy can guarantee a profit or protect against loss.

This article was updated June 8, 2021.

Reference

1. Wachter S and Acolin A. Owning or Renting in the US: Shifting Dynamics of the Housing Market. Penn Institute for Urban Research. 2016 May.

The concept of home ownership has changed for this generation, not only in the logistics of the best way to do it, but also in the desire and demand for owning versus renting. According to the Penn Institute for Urban Research, the U.S. homeownership rate is now at 63.7%, the lowest in 48 years. “Homeownership rates have declined for all demographic age groups. Since 2006, the number of households who own their home in the United States has decreased by 674,000 while the number of renters has increased by over 8 million.”¹

But isn’t owning your own home the American dream? Isn’t it a great investment? If we’re looking strictly at the monthly payment numbers, traditionally paying a mortgage is cheaper than paying rent for the same-size home. That became even more true as home prices dropped in 2007-2008 and as interest rates also dropped over the last several years. Then there’s the age-old concept of “building equity” or “throwing away money on rent.” As a financial planner, I get asked all the time about a home as an investment. It certainly can be, like any investment, if you buy and sell at the right time. But something is only an investment if it grows, and you can’t predict if you’re going to buy and sell your house at the right time. The median price of an existing home sold in March 2021 was $329,100. That’s a 17.2% increase from March 2020. Times are certainly crazy right now in the real estate market.

What many people don’t think about are the other costs, and not just financial costs. Today’s generation is more aware of the added stress and burden of maintaining a home and the money you can sink into it for maintenance, let alone remodeling. Then of course there’s the mortgage interest, property taxes, and insurance that you won’t have with a rental. Lastly, the biggest reason today’s generation is choosing to rent more and more is the flexibility. They want to be more mobile, able to get up and move without having to worry about listing, selling, and possibly owing more than the house is worth, and being stuck. We saw this with many residents that bought a home during residency and then tried to sell when they landed their first job, only to find out they owed more than it was worth because of the real estate market collapse of 2008. Approximately 50% of physicians will leave their first job within 1-3 years, so it’s a gamble that you’ll be able to sell your house when you want to for the price you need.

But what are the benefits of buying? First, there is the age-old argument of building equity. If you stay in your house long enough, and plan to sell it when you retire and downsize, it can definitely be an investment. If you keep a mortgage long enough, eventually you’ll pay it off, and have no payment. Mortgage interest is also tax-deductible. Lastly, there are the intangibles – like being able to put down roots, build a community, and have the ability to remodel and customize your home, a feature not usually available when renting.

Now that I’ve effectively talked you out and back in again, what’s the best way to go about buying a house in today’s crazy market? We’ve seen houses list and sell within a day and get multiple offers well over asking price. It’s a very difficult time to buy, but there are ways to make it easier. First, be clear on what you want in a house, especially location. There’s nothing worse than buyer’s remorse in your primary residence, and that happens more these days when people have to quickly make a decision. Find a good, fee-based financial planner to help you decide how much house fits in your budget and your long-term goals. You’d be surprised how easily we can talk ourselves into paying much more than we had originally decided. Use your financial planner to help avoid emotions getting involved and creeping up your price (especially when multiple offers are involved). A good rule of thumb is for a housing payment to be no more than 33% of your take-home income. This includes principal, interest, and taxes. Or, many planners will use the “2x income” rule of thumb. So if you make $300,000, don’t go over $600,000. Although with today’s low interest rates, there is some more wiggle room on that. Next, get a good referral from someone you trust in looking for a realtor. Real estate is a commission-based job and can have some potential conflicts of interest, so getting a recommendation can help. Or, there are realtors who will work for a flat fee, regardless of how much you pay for a house. That can help reduce the conflict.

You made the offer, you beat out the other bids, and you’re getting a house! How are you paying for it? Hopefully, you already got preapproved. This means finding a good, reputable mortgage professional. Get referrals, shop around, and take your time. Get multiple quotes before you start the underwriting process. They shouldn’t have to pull your credit to give you a fairly accurate estimate of what interest rate you’ll qualify for. Usually, they will give you fixed and variable interest quotes. I normally recommend fixed interest. Because interest rates are so low right now, they’re only going to go up in the future, and if you have a variable rate loan, your payment will go up as interest rates rise.

Is a physician loan a good idea? Depending on your circumstance, it can often be a good deal. Most new attendings don’t have cash saved up for a down payment, and these often don’t require one. And the other big benefit is that they won’t consider your student loan payments when calculating your debt-to-income ratio. Mortgage lenders will look at how much other debt you have when determining an approval. And a conventional mortgage will take your student loan payments into consideration, which means you’ll qualify for a much lower payment and purchase price. In my experience, you want a credit score of around 700 or higher to qualify for these types of loans. The only downside of a physician mortgage is the rates are slightly higher. I encourage you to start the application process early; they’re taking upward of 90 days lately.

As the mortgage is being processed, you’ll have an inspection and appraisal, and as long as those are all favorable, you’re in! Now, should you take any surplus income each month and pay extra on your mortgage to pay it down sooner, or invest it? Everyone’s situation is different, but a good rule of thumb is to look at interest rates on the debt you want to pay off versus expected rate of return on the potential investment. For example, if you have extra money, should you invest it in an SP500 index fund that historically gets 8%-12% per year, or put it on the principal of your mortgage that has an interest rate of 3%? Assuming no other factors or goals, and you just want the best bang for your buck, my money would go toward the investment getting 8%-12% over saving 3% on my mortgage.

Take your time, do your research, and find good professionals. There’s no right answer for everyone, but there are certainly some good practices when walking through the first home decision. Here at FinancialMD, we only work with physicians, and we’re happy to chat if you want some guidance on this. Send me an email and subscribe to our weekly Didactic Minute videos on YouTube for more financial tips for young physicians. Good luck!

Mr. Solitro is a financial planner and CEO of FinancialMD. He has no other conflicts of interest.

Investment advisory services offered through FinancialMD, a registered investment adviser. Registration as an investment adviser does not imply a certain level of skill or training. This article is provided for informational purposes only and nothing contained herein should be construed as a solicitation to buy or sell any products. Advisory services are offered only to clients and prospective clients in places where FinancialMD and its investment adviser representatives are registered or exempt from registration. Investing involves the risk of loss of principal. Past performance is no guarantee of future performance and no investment strategy can guarantee a profit or protect against loss.

This article was updated June 8, 2021.

Reference

1. Wachter S and Acolin A. Owning or Renting in the US: Shifting Dynamics of the Housing Market. Penn Institute for Urban Research. 2016 May.

The concept of home ownership has changed for this generation, not only in the logistics of the best way to do it, but also in the desire and demand for owning versus renting. According to the Penn Institute for Urban Research, the U.S. homeownership rate is now at 63.7%, the lowest in 48 years. “Homeownership rates have declined for all demographic age groups. Since 2006, the number of households who own their home in the United States has decreased by 674,000 while the number of renters has increased by over 8 million.”¹

But isn’t owning your own home the American dream? Isn’t it a great investment? If we’re looking strictly at the monthly payment numbers, traditionally paying a mortgage is cheaper than paying rent for the same-size home. That became even more true as home prices dropped in 2007-2008 and as interest rates also dropped over the last several years. Then there’s the age-old concept of “building equity” or “throwing away money on rent.” As a financial planner, I get asked all the time about a home as an investment. It certainly can be, like any investment, if you buy and sell at the right time. But something is only an investment if it grows, and you can’t predict if you’re going to buy and sell your house at the right time. The median price of an existing home sold in March 2021 was $329,100. That’s a 17.2% increase from March 2020. Times are certainly crazy right now in the real estate market.

What many people don’t think about are the other costs, and not just financial costs. Today’s generation is more aware of the added stress and burden of maintaining a home and the money you can sink into it for maintenance, let alone remodeling. Then of course there’s the mortgage interest, property taxes, and insurance that you won’t have with a rental. Lastly, the biggest reason today’s generation is choosing to rent more and more is the flexibility. They want to be more mobile, able to get up and move without having to worry about listing, selling, and possibly owing more than the house is worth, and being stuck. We saw this with many residents that bought a home during residency and then tried to sell when they landed their first job, only to find out they owed more than it was worth because of the real estate market collapse of 2008. Approximately 50% of physicians will leave their first job within 1-3 years, so it’s a gamble that you’ll be able to sell your house when you want to for the price you need.

But what are the benefits of buying? First, there is the age-old argument of building equity. If you stay in your house long enough, and plan to sell it when you retire and downsize, it can definitely be an investment. If you keep a mortgage long enough, eventually you’ll pay it off, and have no payment. Mortgage interest is also tax-deductible. Lastly, there are the intangibles – like being able to put down roots, build a community, and have the ability to remodel and customize your home, a feature not usually available when renting.

Now that I’ve effectively talked you out and back in again, what’s the best way to go about buying a house in today’s crazy market? We’ve seen houses list and sell within a day and get multiple offers well over asking price. It’s a very difficult time to buy, but there are ways to make it easier. First, be clear on what you want in a house, especially location. There’s nothing worse than buyer’s remorse in your primary residence, and that happens more these days when people have to quickly make a decision. Find a good, fee-based financial planner to help you decide how much house fits in your budget and your long-term goals. You’d be surprised how easily we can talk ourselves into paying much more than we had originally decided. Use your financial planner to help avoid emotions getting involved and creeping up your price (especially when multiple offers are involved). A good rule of thumb is for a housing payment to be no more than 33% of your take-home income. This includes principal, interest, and taxes. Or, many planners will use the “2x income” rule of thumb. So if you make $300,000, don’t go over $600,000. Although with today’s low interest rates, there is some more wiggle room on that. Next, get a good referral from someone you trust in looking for a realtor. Real estate is a commission-based job and can have some potential conflicts of interest, so getting a recommendation can help. Or, there are realtors who will work for a flat fee, regardless of how much you pay for a house. That can help reduce the conflict.

You made the offer, you beat out the other bids, and you’re getting a house! How are you paying for it? Hopefully, you already got preapproved. This means finding a good, reputable mortgage professional. Get referrals, shop around, and take your time. Get multiple quotes before you start the underwriting process. They shouldn’t have to pull your credit to give you a fairly accurate estimate of what interest rate you’ll qualify for. Usually, they will give you fixed and variable interest quotes. I normally recommend fixed interest. Because interest rates are so low right now, they’re only going to go up in the future, and if you have a variable rate loan, your payment will go up as interest rates rise.

Is a physician loan a good idea? Depending on your circumstance, it can often be a good deal. Most new attendings don’t have cash saved up for a down payment, and these often don’t require one. And the other big benefit is that they won’t consider your student loan payments when calculating your debt-to-income ratio. Mortgage lenders will look at how much other debt you have when determining an approval. And a conventional mortgage will take your student loan payments into consideration, which means you’ll qualify for a much lower payment and purchase price. In my experience, you want a credit score of around 700 or higher to qualify for these types of loans. The only downside of a physician mortgage is the rates are slightly higher. I encourage you to start the application process early; they’re taking upward of 90 days lately.

As the mortgage is being processed, you’ll have an inspection and appraisal, and as long as those are all favorable, you’re in! Now, should you take any surplus income each month and pay extra on your mortgage to pay it down sooner, or invest it? Everyone’s situation is different, but a good rule of thumb is to look at interest rates on the debt you want to pay off versus expected rate of return on the potential investment. For example, if you have extra money, should you invest it in an SP500 index fund that historically gets 8%-12% per year, or put it on the principal of your mortgage that has an interest rate of 3%? Assuming no other factors or goals, and you just want the best bang for your buck, my money would go toward the investment getting 8%-12% over saving 3% on my mortgage.

Take your time, do your research, and find good professionals. There’s no right answer for everyone, but there are certainly some good practices when walking through the first home decision. Here at FinancialMD, we only work with physicians, and we’re happy to chat if you want some guidance on this. Send me an email and subscribe to our weekly Didactic Minute videos on YouTube for more financial tips for young physicians. Good luck!

Mr. Solitro is a financial planner and CEO of FinancialMD. He has no other conflicts of interest.

Investment advisory services offered through FinancialMD, a registered investment adviser. Registration as an investment adviser does not imply a certain level of skill or training. This article is provided for informational purposes only and nothing contained herein should be construed as a solicitation to buy or sell any products. Advisory services are offered only to clients and prospective clients in places where FinancialMD and its investment adviser representatives are registered or exempt from registration. Investing involves the risk of loss of principal. Past performance is no guarantee of future performance and no investment strategy can guarantee a profit or protect against loss.

This article was updated June 8, 2021.

Reference

1. Wachter S and Acolin A. Owning or Renting in the US: Shifting Dynamics of the Housing Market. Penn Institute for Urban Research. 2016 May.

Patients overwhelmingly found telemedicine care for headache a satisfactory and beneficial experience during the COVID-19 pandemic, according to a study presented at the American Headache Society’s 2021 annual meeting. Most patients who used telemedicine said they would like to continue using it after the pandemic, though the study also revealed barriers to care for a small percentage of respondents.

“Telemedicine minimizes the physical and geographic barriers to health care, preserves personal protective equipment, and prevents the spread of COVID-19 by allowing encounters to happen in a socially distanced way,” said Chia-Chun Chiang, MD, assistant professor of neurology at Mayo Clinic in Rochester, Minn. “Telemedicine provides patients with opportunities to gain better control of their headache disorders while not having to commit to the time to travel and risk of exposure to COVID-19.” If insurance coverage for virtual care were rolled back, “patients and multiple levels of health care providers would be significantly affected,” she said.

The research relied on findings from a 15-question survey distributed by the nonprofit American Migraine Foundation through email and social media to more than 100,000 people. Among the 1,172 patients who responded to the survey, 1,098 had complete responses, and 86.6% were female.

The vast majority of these patients (93.8%) had had a previous diagnosis of a headache. Just over half (57.5%) said they used telemedicine during the study period, with most of those visits (85.5%) being follow-up care and 14.5% involving a new patient visit.

Among those who did not use telemedicine, most (56.1%) said they didn’t need a visit. However, a quarter of these respondents (25.2%) said they didn’t know telemedicine was an option, and 12.9% said they would have preferred telemedicine but it wasn’t offered by their doctors. A smaller proportion (3.5%) said they wanted to use virtual care but that their insurance did not cover it, and nearly as many (2.2%) said they wanted telemedicine but didn’t have the technology needed to use it.

“The COVID-19 pandemic has highlighted that reliable Internet service has contributed to disparities in access in many ways, including health care via telemedicine,” Dr. Chiang said. “Those who are not able to afford Internet, lack proficiency in the use of technology, or have cognitive impairment might not be able to utilize telemedicine.”

Among those who did receive telemedicine care for headache, about a third (34.4%) received care from a general neurologist while 43.7% saw a headache specialist and nearly a third (30.7%) saw a primary care provider. The remaining visits included 11.3% who saw headache nurse practitioners and 3.2% who saw headache nurses.

Most patients did not have a new or changed diagnosis at their visit; only 7.4% received a new headache diagnosis during their telemedicine appointment. Though 43.7% had no change to their therapy, a little more than half of patients (52.4%) received a new treatment, a finding that caught the interest of Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and past president of the International Headache Society.

“The techniques used [in virtual visits] were good enough for the caregiver to make critical decisions about how the patient was doing and what new treatment might be better for them,” said Dr. Rapoport, who was not involved in the research. “I believe that most headache specialists will gradually resume in office visits,” he said, but “this study shows it would be okay for some or most of the revisits to continue to be done virtually.”

The vast majority of patients rated their care as “very good” (62.1%) or “good” (20.7%). Less satisfied responses included 10.5% who felt their experience was “fair,” 3.6% who said it was “poor,” and 3.1% who gave other responses.

These results fit with the experience of Dr. Rapoport and of Paul B. Rizzoli, MD, associate professor of neurology at Harvard Medical School and clinical director of the John R. Graham Headache Center at Brigham and Women’s Faulkner Hospital, both in Boston.

“Telemedicine worked better than we anticipated,” said Dr. Rizzoli when asked for comment. “I was especially surprised how comfortable I became with its use for many, but not all, new patients. While I don’t expect it to replace in-person visits, I do expect that it will and should be a permanent part of our care going forward, especially for follow-up visits.”

The findings supported that expectation as well: An overwhelming majority of those who responded to the survey (89.8%) also said they would like to keep receiving telemedicine care for their headache care and treatment. This percentage was split evenly between those who said they would like to always receive care virtually and those who would only want to use it for some appointments. A smaller proportion said they did not want to keep using virtual care (7.1%) or weren’t sure (3.1%).

“Telemedicine has become an essential tool for patients and a wide variety of clinicians,” Dr. Chiang reported during her presentation. “Telemedicine facilitated headache care for many patients during the COVID-19 pandemic, resulting in high patient satisfaction rates and a desire to continue to utilize telemedicine for future headache care for those who responded to the online survey.”

Dr. Rapoport noted that a particular benefit of telemedicine in his practice is avoiding transportation issues.

“In Santa Monica and Los Angeles, my patients coming from 10 or more miles away usually have to contend with difficult traffic, which created stress and often made them late and upset the office schedule,” Dr. Rapoport said. “I found that virtual visits were almost always shorter, on time, and were as effective for the patient as an in-person visit.”

Dr. Chiang drew attention, however, to the barriers to care found in the study, including not having or knowing of telemedicine as an option, and not having access to the technology or insurance coverage needed to take advantage of it. She listed three ways to address those challenges and increase health care accessibility to patients:
 

• Expand insurance coverage to reimburse telemedicine even after the pandemic.
• Widely promote and broadcast the use of virtual care.
• Make Internet access a priority as a necessity in society and expand access.

Dr. Rizzoli also noted some ways to improve telemedicine. “We could easily develop improved means of delivering vital signs and other bio-information over telemedicine to improve decision-making,” he said. “A difficult task going forward will be to fix legal questions associated with virtual visits across state lines which, especially in the small New England states, come up frequently and are currently illegal.”

Dr. Rapoport noted ways that patients can facilitate effective telemedicine visits. “Doctors should insist that patients keep careful records of their headaches, triggers, medicines, etc., either on paper or preferably via an app on their smartphones, which is usually always accessible,” Dr. Rapoport said. “With good data and a good electronic connection, the visit should go well.”

Among the study’s limitations were a comparatively small response rate (1.11% of those invited to participate) and ascertainment bias.

“The take-home message from the experience is that this turns out to be an effective, efficient and accepted means of delivering care that should be developed further,” Dr. Rizzoli said.

No external funding was noted. Dr. Chiang and Dr. Rizzoli had no disclosures. Dr. Rapoport has advised AbbVie, Amgen, Biohaven, Cala Health, Satsuma, Teva Pharmaceutical Industries, Theranica, Xoc and Zosano, and is on the speakers bureau of AbbVie, Amgen, Biohaven, Lundbeck and Teva Pharmaceutical Industries.

Patients overwhelmingly found telemedicine care for headache a satisfactory and beneficial experience during the COVID-19 pandemic, according to a study presented at the American Headache Society’s 2021 annual meeting. Most patients who used telemedicine said they would like to continue using it after the pandemic, though the study also revealed barriers to care for a small percentage of respondents.

“Telemedicine minimizes the physical and geographic barriers to health care, preserves personal protective equipment, and prevents the spread of COVID-19 by allowing encounters to happen in a socially distanced way,” said Chia-Chun Chiang, MD, assistant professor of neurology at Mayo Clinic in Rochester, Minn. “Telemedicine provides patients with opportunities to gain better control of their headache disorders while not having to commit to the time to travel and risk of exposure to COVID-19.” If insurance coverage for virtual care were rolled back, “patients and multiple levels of health care providers would be significantly affected,” she said.

The research relied on findings from a 15-question survey distributed by the nonprofit American Migraine Foundation through email and social media to more than 100,000 people. Among the 1,172 patients who responded to the survey, 1,098 had complete responses, and 86.6% were female.

The vast majority of these patients (93.8%) had had a previous diagnosis of a headache. Just over half (57.5%) said they used telemedicine during the study period, with most of those visits (85.5%) being follow-up care and 14.5% involving a new patient visit.

Among those who did not use telemedicine, most (56.1%) said they didn’t need a visit. However, a quarter of these respondents (25.2%) said they didn’t know telemedicine was an option, and 12.9% said they would have preferred telemedicine but it wasn’t offered by their doctors. A smaller proportion (3.5%) said they wanted to use virtual care but that their insurance did not cover it, and nearly as many (2.2%) said they wanted telemedicine but didn’t have the technology needed to use it.

“The COVID-19 pandemic has highlighted that reliable Internet service has contributed to disparities in access in many ways, including health care via telemedicine,” Dr. Chiang said. “Those who are not able to afford Internet, lack proficiency in the use of technology, or have cognitive impairment might not be able to utilize telemedicine.”

Among those who did receive telemedicine care for headache, about a third (34.4%) received care from a general neurologist while 43.7% saw a headache specialist and nearly a third (30.7%) saw a primary care provider. The remaining visits included 11.3% who saw headache nurse practitioners and 3.2% who saw headache nurses.

Most patients did not have a new or changed diagnosis at their visit; only 7.4% received a new headache diagnosis during their telemedicine appointment. Though 43.7% had no change to their therapy, a little more than half of patients (52.4%) received a new treatment, a finding that caught the interest of Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and past president of the International Headache Society.

“The techniques used [in virtual visits] were good enough for the caregiver to make critical decisions about how the patient was doing and what new treatment might be better for them,” said Dr. Rapoport, who was not involved in the research. “I believe that most headache specialists will gradually resume in office visits,” he said, but “this study shows it would be okay for some or most of the revisits to continue to be done virtually.”

The vast majority of patients rated their care as “very good” (62.1%) or “good” (20.7%). Less satisfied responses included 10.5% who felt their experience was “fair,” 3.6% who said it was “poor,” and 3.1% who gave other responses.

These results fit with the experience of Dr. Rapoport and of Paul B. Rizzoli, MD, associate professor of neurology at Harvard Medical School and clinical director of the John R. Graham Headache Center at Brigham and Women’s Faulkner Hospital, both in Boston.

“Telemedicine worked better than we anticipated,” said Dr. Rizzoli when asked for comment. “I was especially surprised how comfortable I became with its use for many, but not all, new patients. While I don’t expect it to replace in-person visits, I do expect that it will and should be a permanent part of our care going forward, especially for follow-up visits.”

The findings supported that expectation as well: An overwhelming majority of those who responded to the survey (89.8%) also said they would like to keep receiving telemedicine care for their headache care and treatment. This percentage was split evenly between those who said they would like to always receive care virtually and those who would only want to use it for some appointments. A smaller proportion said they did not want to keep using virtual care (7.1%) or weren’t sure (3.1%).

“Telemedicine has become an essential tool for patients and a wide variety of clinicians,” Dr. Chiang reported during her presentation. “Telemedicine facilitated headache care for many patients during the COVID-19 pandemic, resulting in high patient satisfaction rates and a desire to continue to utilize telemedicine for future headache care for those who responded to the online survey.”

Dr. Rapoport noted that a particular benefit of telemedicine in his practice is avoiding transportation issues.

“In Santa Monica and Los Angeles, my patients coming from 10 or more miles away usually have to contend with difficult traffic, which created stress and often made them late and upset the office schedule,” Dr. Rapoport said. “I found that virtual visits were almost always shorter, on time, and were as effective for the patient as an in-person visit.”

Dr. Chiang drew attention, however, to the barriers to care found in the study, including not having or knowing of telemedicine as an option, and not having access to the technology or insurance coverage needed to take advantage of it. She listed three ways to address those challenges and increase health care accessibility to patients:
 

• Expand insurance coverage to reimburse telemedicine even after the pandemic.
• Widely promote and broadcast the use of virtual care.
• Make Internet access a priority as a necessity in society and expand access.

Dr. Rizzoli also noted some ways to improve telemedicine. “We could easily develop improved means of delivering vital signs and other bio-information over telemedicine to improve decision-making,” he said. “A difficult task going forward will be to fix legal questions associated with virtual visits across state lines which, especially in the small New England states, come up frequently and are currently illegal.”

Dr. Rapoport noted ways that patients can facilitate effective telemedicine visits. “Doctors should insist that patients keep careful records of their headaches, triggers, medicines, etc., either on paper or preferably via an app on their smartphones, which is usually always accessible,” Dr. Rapoport said. “With good data and a good electronic connection, the visit should go well.”

Among the study’s limitations were a comparatively small response rate (1.11% of those invited to participate) and ascertainment bias.

“The take-home message from the experience is that this turns out to be an effective, efficient and accepted means of delivering care that should be developed further,” Dr. Rizzoli said.

No external funding was noted. Dr. Chiang and Dr. Rizzoli had no disclosures. Dr. Rapoport has advised AbbVie, Amgen, Biohaven, Cala Health, Satsuma, Teva Pharmaceutical Industries, Theranica, Xoc and Zosano, and is on the speakers bureau of AbbVie, Amgen, Biohaven, Lundbeck and Teva Pharmaceutical Industries.

Patients overwhelmingly found telemedicine care for headache a satisfactory and beneficial experience during the COVID-19 pandemic, according to a study presented at the American Headache Society’s 2021 annual meeting. Most patients who used telemedicine said they would like to continue using it after the pandemic, though the study also revealed barriers to care for a small percentage of respondents.

“Telemedicine minimizes the physical and geographic barriers to health care, preserves personal protective equipment, and prevents the spread of COVID-19 by allowing encounters to happen in a socially distanced way,” said Chia-Chun Chiang, MD, assistant professor of neurology at Mayo Clinic in Rochester, Minn. “Telemedicine provides patients with opportunities to gain better control of their headache disorders while not having to commit to the time to travel and risk of exposure to COVID-19.” If insurance coverage for virtual care were rolled back, “patients and multiple levels of health care providers would be significantly affected,” she said.

The research relied on findings from a 15-question survey distributed by the nonprofit American Migraine Foundation through email and social media to more than 100,000 people. Among the 1,172 patients who responded to the survey, 1,098 had complete responses, and 86.6% were female.

The vast majority of these patients (93.8%) had had a previous diagnosis of a headache. Just over half (57.5%) said they used telemedicine during the study period, with most of those visits (85.5%) being follow-up care and 14.5% involving a new patient visit.

Among those who did not use telemedicine, most (56.1%) said they didn’t need a visit. However, a quarter of these respondents (25.2%) said they didn’t know telemedicine was an option, and 12.9% said they would have preferred telemedicine but it wasn’t offered by their doctors. A smaller proportion (3.5%) said they wanted to use virtual care but that their insurance did not cover it, and nearly as many (2.2%) said they wanted telemedicine but didn’t have the technology needed to use it.

“The COVID-19 pandemic has highlighted that reliable Internet service has contributed to disparities in access in many ways, including health care via telemedicine,” Dr. Chiang said. “Those who are not able to afford Internet, lack proficiency in the use of technology, or have cognitive impairment might not be able to utilize telemedicine.”

Among those who did receive telemedicine care for headache, about a third (34.4%) received care from a general neurologist while 43.7% saw a headache specialist and nearly a third (30.7%) saw a primary care provider. The remaining visits included 11.3% who saw headache nurse practitioners and 3.2% who saw headache nurses.

Most patients did not have a new or changed diagnosis at their visit; only 7.4% received a new headache diagnosis during their telemedicine appointment. Though 43.7% had no change to their therapy, a little more than half of patients (52.4%) received a new treatment, a finding that caught the interest of Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and past president of the International Headache Society.

“The techniques used [in virtual visits] were good enough for the caregiver to make critical decisions about how the patient was doing and what new treatment might be better for them,” said Dr. Rapoport, who was not involved in the research. “I believe that most headache specialists will gradually resume in office visits,” he said, but “this study shows it would be okay for some or most of the revisits to continue to be done virtually.”

The vast majority of patients rated their care as “very good” (62.1%) or “good” (20.7%). Less satisfied responses included 10.5% who felt their experience was “fair,” 3.6% who said it was “poor,” and 3.1% who gave other responses.

These results fit with the experience of Dr. Rapoport and of Paul B. Rizzoli, MD, associate professor of neurology at Harvard Medical School and clinical director of the John R. Graham Headache Center at Brigham and Women’s Faulkner Hospital, both in Boston.

“Telemedicine worked better than we anticipated,” said Dr. Rizzoli when asked for comment. “I was especially surprised how comfortable I became with its use for many, but not all, new patients. While I don’t expect it to replace in-person visits, I do expect that it will and should be a permanent part of our care going forward, especially for follow-up visits.”

The findings supported that expectation as well: An overwhelming majority of those who responded to the survey (89.8%) also said they would like to keep receiving telemedicine care for their headache care and treatment. This percentage was split evenly between those who said they would like to always receive care virtually and those who would only want to use it for some appointments. A smaller proportion said they did not want to keep using virtual care (7.1%) or weren’t sure (3.1%).

“Telemedicine has become an essential tool for patients and a wide variety of clinicians,” Dr. Chiang reported during her presentation. “Telemedicine facilitated headache care for many patients during the COVID-19 pandemic, resulting in high patient satisfaction rates and a desire to continue to utilize telemedicine for future headache care for those who responded to the online survey.”

Dr. Rapoport noted that a particular benefit of telemedicine in his practice is avoiding transportation issues.

“In Santa Monica and Los Angeles, my patients coming from 10 or more miles away usually have to contend with difficult traffic, which created stress and often made them late and upset the office schedule,” Dr. Rapoport said. “I found that virtual visits were almost always shorter, on time, and were as effective for the patient as an in-person visit.”

Dr. Chiang drew attention, however, to the barriers to care found in the study, including not having or knowing of telemedicine as an option, and not having access to the technology or insurance coverage needed to take advantage of it. She listed three ways to address those challenges and increase health care accessibility to patients:
 

• Expand insurance coverage to reimburse telemedicine even after the pandemic.
• Widely promote and broadcast the use of virtual care.
• Make Internet access a priority as a necessity in society and expand access.

Dr. Rizzoli also noted some ways to improve telemedicine. “We could easily develop improved means of delivering vital signs and other bio-information over telemedicine to improve decision-making,” he said. “A difficult task going forward will be to fix legal questions associated with virtual visits across state lines which, especially in the small New England states, come up frequently and are currently illegal.”

Dr. Rapoport noted ways that patients can facilitate effective telemedicine visits. “Doctors should insist that patients keep careful records of their headaches, triggers, medicines, etc., either on paper or preferably via an app on their smartphones, which is usually always accessible,” Dr. Rapoport said. “With good data and a good electronic connection, the visit should go well.”

Among the study’s limitations were a comparatively small response rate (1.11% of those invited to participate) and ascertainment bias.

“The take-home message from the experience is that this turns out to be an effective, efficient and accepted means of delivering care that should be developed further,” Dr. Rizzoli said.

No external funding was noted. Dr. Chiang and Dr. Rizzoli had no disclosures. Dr. Rapoport has advised AbbVie, Amgen, Biohaven, Cala Health, Satsuma, Teva Pharmaceutical Industries, Theranica, Xoc and Zosano, and is on the speakers bureau of AbbVie, Amgen, Biohaven, Lundbeck and Teva Pharmaceutical Industries.

Amid significant controversy, the U.S. Food and Drug Administration (FDA) has approved the anti-amyloid agent aducanumab (Biogen, Eisai) for the treatment of Alzheimer’s disease, disregarding the recommendation by its own advisory panel not to approve the drug.

In November, the Peripheral and Central Nervous System Drugs Advisory Committee voted eight to one against approving the drug because, based on clinical trial results, evidence of efficacy was not strong enough. Two other members said they were uncertain on the issue of efficacy.

In a company release Michel Vounatsos, Biogen’s Chief Executive Officer, said, “this historic moment is the culmination of more than a decade of groundbreaking research in the complex field of Alzheimer’s disease. We believe this first-in-class medicine will transform the treatment of people living with Alzheimer’s disease and spark continuous innovation in the years to come.
 

Rocky road

The road to approval has been extremely rocky for aducanumab, an anti-amyloid-beta human monoclonal antibody, previously known as BIIB037.

As reported by this news organization, two phase 3 trials evaluating the drug were initially scrapped in March 2019 because of interim futility analysis. At the time, Biogen released a statement saying that aducanumab was unlikely to meet primary endpoints in the ENGAGE and EMERGE randomized controlled trials.

However, in an about-face 7 months later, Biogen and Eisai announced that a  new analysis showed the drug met its primary endpoint of reduction in clinical decline, including cognition and function, in the EMERGE trial.

Although ENGAGE still didn’t meet its primary endpoint, data from its new analysis “supported” the EMERGE findings, the drug companies said at the time.

However, 1 year later, a majority of the members of the FDA’s advisory panel were against the drug’s approval. Details of that decision were published online March 30 in the Journal of the American Medical Association.

As reported by this news organization, a Viewpoint written by three of the committee members notes that results from the drug’s only large positive clinical trial fell short.

“There is no persuasive evidence to support approval of aducanumab at this time,” they write.

Groups such as Public Citizen’s Health Research Group not only agree with the Viewpoint’s authors, they also criticized the FDA for its collaboration with the drug’s manufacturers on briefing documents and more.

On April 1, Health Research Group members sent a letter to the U.S. Secretary of Health and Human Services requesting the temporary suspension of the FDA’s neuroscience chief, Bill Dunn, MD, because of his role in supervising the collaboration.
 

Alzheimer association weighs in

The Alzheimer’s Association has been a proponent of the drug throughout its development.

Ahead of today’s news, the organization noted in a statement that a decision to approve “would be historic” because it would make aducanumab “the first drug to slow Alzheimer’s disease” and would mark the beginning of a new future for AD treatments.

“The Alzheimer’s Association urgently supports FDA approval of the treatment based on clinical trial results that showed a 22% reduction in cognitive and function decline — something that could make a meaningful difference” for patients with AD, it said.

Kristen Clifford, chief program officer for the Alzheimer’s Association, said in an interview at the time that approval would be considered a “victory” for patients with AD and for the field overall.

“For individuals who would potentially be eligible for the treatment, this drug could mean more quality time. Slowing decline, particularly in early diagnosis, could add weeks or months or maybe even years of active life,” Clifford said.

“If approved, this would really be a landmark moment. And it could provide hope for those living with Alzheimer’s and their families,” she added.

Clifford noted that approval of this type of drug would also underscore the importance of early detection for AD. “This treatment would encourage earlier diagnosis of the disease,” she said.

In a new statement released just after approval for aducanumab was announced, the organization said that today’s news is a win-win for all patients with AD and their families.

A version of this article first appeared on Medscape.com.

Amid significant controversy, the U.S. Food and Drug Administration (FDA) has approved the anti-amyloid agent aducanumab (Biogen, Eisai) for the treatment of Alzheimer’s disease, disregarding the recommendation by its own advisory panel not to approve the drug.

In November, the Peripheral and Central Nervous System Drugs Advisory Committee voted eight to one against approving the drug because, based on clinical trial results, evidence of efficacy was not strong enough. Two other members said they were uncertain on the issue of efficacy.

In a company release Michel Vounatsos, Biogen’s Chief Executive Officer, said, “this historic moment is the culmination of more than a decade of groundbreaking research in the complex field of Alzheimer’s disease. We believe this first-in-class medicine will transform the treatment of people living with Alzheimer’s disease and spark continuous innovation in the years to come.
 

Rocky road

The road to approval has been extremely rocky for aducanumab, an anti-amyloid-beta human monoclonal antibody, previously known as BIIB037.

As reported by this news organization, two phase 3 trials evaluating the drug were initially scrapped in March 2019 because of interim futility analysis. At the time, Biogen released a statement saying that aducanumab was unlikely to meet primary endpoints in the ENGAGE and EMERGE randomized controlled trials.

However, in an about-face 7 months later, Biogen and Eisai announced that a  new analysis showed the drug met its primary endpoint of reduction in clinical decline, including cognition and function, in the EMERGE trial.

Although ENGAGE still didn’t meet its primary endpoint, data from its new analysis “supported” the EMERGE findings, the drug companies said at the time.

However, 1 year later, a majority of the members of the FDA’s advisory panel were against the drug’s approval. Details of that decision were published online March 30 in the Journal of the American Medical Association.

As reported by this news organization, a Viewpoint written by three of the committee members notes that results from the drug’s only large positive clinical trial fell short.

“There is no persuasive evidence to support approval of aducanumab at this time,” they write.

Groups such as Public Citizen’s Health Research Group not only agree with the Viewpoint’s authors, they also criticized the FDA for its collaboration with the drug’s manufacturers on briefing documents and more.

On April 1, Health Research Group members sent a letter to the U.S. Secretary of Health and Human Services requesting the temporary suspension of the FDA’s neuroscience chief, Bill Dunn, MD, because of his role in supervising the collaboration.
 

Alzheimer association weighs in

The Alzheimer’s Association has been a proponent of the drug throughout its development.

Ahead of today’s news, the organization noted in a statement that a decision to approve “would be historic” because it would make aducanumab “the first drug to slow Alzheimer’s disease” and would mark the beginning of a new future for AD treatments.

“The Alzheimer’s Association urgently supports FDA approval of the treatment based on clinical trial results that showed a 22% reduction in cognitive and function decline — something that could make a meaningful difference” for patients with AD, it said.

Kristen Clifford, chief program officer for the Alzheimer’s Association, said in an interview at the time that approval would be considered a “victory” for patients with AD and for the field overall.

“For individuals who would potentially be eligible for the treatment, this drug could mean more quality time. Slowing decline, particularly in early diagnosis, could add weeks or months or maybe even years of active life,” Clifford said.

“If approved, this would really be a landmark moment. And it could provide hope for those living with Alzheimer’s and their families,” she added.

Clifford noted that approval of this type of drug would also underscore the importance of early detection for AD. “This treatment would encourage earlier diagnosis of the disease,” she said.

In a new statement released just after approval for aducanumab was announced, the organization said that today’s news is a win-win for all patients with AD and their families.

A version of this article first appeared on Medscape.com.

Amid significant controversy, the U.S. Food and Drug Administration (FDA) has approved the anti-amyloid agent aducanumab (Biogen, Eisai) for the treatment of Alzheimer’s disease, disregarding the recommendation by its own advisory panel not to approve the drug.

In November, the Peripheral and Central Nervous System Drugs Advisory Committee voted eight to one against approving the drug because, based on clinical trial results, evidence of efficacy was not strong enough. Two other members said they were uncertain on the issue of efficacy.

In a company release Michel Vounatsos, Biogen’s Chief Executive Officer, said, “this historic moment is the culmination of more than a decade of groundbreaking research in the complex field of Alzheimer’s disease. We believe this first-in-class medicine will transform the treatment of people living with Alzheimer’s disease and spark continuous innovation in the years to come.
 

Rocky road

The road to approval has been extremely rocky for aducanumab, an anti-amyloid-beta human monoclonal antibody, previously known as BIIB037.

As reported by this news organization, two phase 3 trials evaluating the drug were initially scrapped in March 2019 because of interim futility analysis. At the time, Biogen released a statement saying that aducanumab was unlikely to meet primary endpoints in the ENGAGE and EMERGE randomized controlled trials.

However, in an about-face 7 months later, Biogen and Eisai announced that a  new analysis showed the drug met its primary endpoint of reduction in clinical decline, including cognition and function, in the EMERGE trial.

Although ENGAGE still didn’t meet its primary endpoint, data from its new analysis “supported” the EMERGE findings, the drug companies said at the time.

However, 1 year later, a majority of the members of the FDA’s advisory panel were against the drug’s approval. Details of that decision were published online March 30 in the Journal of the American Medical Association.

As reported by this news organization, a Viewpoint written by three of the committee members notes that results from the drug’s only large positive clinical trial fell short.

“There is no persuasive evidence to support approval of aducanumab at this time,” they write.

Groups such as Public Citizen’s Health Research Group not only agree with the Viewpoint’s authors, they also criticized the FDA for its collaboration with the drug’s manufacturers on briefing documents and more.

On April 1, Health Research Group members sent a letter to the U.S. Secretary of Health and Human Services requesting the temporary suspension of the FDA’s neuroscience chief, Bill Dunn, MD, because of his role in supervising the collaboration.
 

Alzheimer association weighs in

The Alzheimer’s Association has been a proponent of the drug throughout its development.

Ahead of today’s news, the organization noted in a statement that a decision to approve “would be historic” because it would make aducanumab “the first drug to slow Alzheimer’s disease” and would mark the beginning of a new future for AD treatments.

“The Alzheimer’s Association urgently supports FDA approval of the treatment based on clinical trial results that showed a 22% reduction in cognitive and function decline — something that could make a meaningful difference” for patients with AD, it said.

Kristen Clifford, chief program officer for the Alzheimer’s Association, said in an interview at the time that approval would be considered a “victory” for patients with AD and for the field overall.

“For individuals who would potentially be eligible for the treatment, this drug could mean more quality time. Slowing decline, particularly in early diagnosis, could add weeks or months or maybe even years of active life,” Clifford said.

“If approved, this would really be a landmark moment. And it could provide hope for those living with Alzheimer’s and their families,” she added.

Clifford noted that approval of this type of drug would also underscore the importance of early detection for AD. “This treatment would encourage earlier diagnosis of the disease,” she said.

In a new statement released just after approval for aducanumab was announced, the organization said that today’s news is a win-win for all patients with AD and their families.

A version of this article first appeared on Medscape.com.

A phase 2 study of the anti-calcitonin gene–related peptide (CGRP) antibody fremanezumab found no benefit of treatment in persistent posttraumatic headache. Anti-CGRP therapy had been predicted to be effective, given its history of improving other forms of headache, and preclinical studies had suggested that CGRP plays a role in late pain sensitization that can occur after mild brain injuries.

“There was a decrease in migraine headache days of moderate or severe intensity in both groups. But the difference between fremanezumab and placebo treatment was not statistically significant, either looking at that on a monthly basis or over the total 12 weeks of treatment,” Egilius L.H. Spierings, MD, PhD, said during his presentation of the results at the American Headache Society’s 2021 annual meeting. Dr. Spierings is medical director of the Boston Headache Institute.
 

Disappointing findings

“That’s sad. It’s just dreadful news,” Stewart J. Tepper, MD, professor of neurology at Geisel School of Medicine at Dartmouth, Hanover, N.H., said in an interview. Dr. Tepper was not involved in the study. The results suggest that CGRP mechanisms may not be relevant to persistent posttraumatic headache, but it could still play a role at onset. “We have to rethink this. Either it’s that chronic, persistent posttraumatic headache does not have a CGRP biology, or it’s that you have to get to them earlier [in the disease process],” he said.

The negative results were surprising, according to Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and former president of the International Headache Society. He noted that the study was small, and the researchers were unable to conduct subgroup analyses. “Posttraumatic headaches are usually broken down into those that phenotypically look like migraine, or phenotypically look like tension-type headache. It would have been nice to know if most of them had what clinically appears to be tension-type headache, and maybe that’s why they didn’t respond. Or did most of them have a migraine phenotype, and then it would be a little more surprising that they didn’t respond,” Dr. Rapoport said in an interview.

As a result, he believes that further studies might show that fremanezumab is an effective treatment for posttraumatic headache. “I would not give up on it. I expect that a larger study with better power, and a better idea of exactly what was wrong with the patients, might end up being a positive study,” he said.

Although most posttraumatic headaches resolve within weeks or months, some can linger or become chronic for years. Pain medication is often prescribed but should not be, according to Dr. Rapoport, because it can lead to medication overuse headache that worsens the problem. “So we badly need a good temporary preventive treatment. The thought of giving our newest, most effective preventive medications, with few adverse events, is a good one. It just didn’t seem to work in this fairly small and underpowered study,” he said.
 

The phase 2 trial

The trial included 87 patients with new-onset or significant worsening of headache following a minor traumatic brain injury or concussion, who were randomized to treatment with 675 mg subcutaneous fremanezumab once monthly, or placebo. The average elapsed time since the trauma was 8.1 years in the placebo group and 9.3 years in the fremanezumab arm. The average number of moderate to severe headache days was 18.5 days in the placebo group and 18.4 days in the fremanezumab group. The initial 12-week randomized period was followed by an open-label period in which patients on placebo received the study drug.

After 12 weeks of treatment, there was a greater decrease in moderate to severe headache days in the placebo arm, though the difference was not statistically significant (–5.1 versus –3.6 days; P = .1876). At 1 month, the two groups were similar (–4 days placebo versus –3.6 days fremanezumab), but there was a greater reduction in the placebo arm at 2 months (–6.7 versus –3.7 days) and 3 months (–7.21 versus –5.2 days).

A secondary endpoint was the proportion of patients who experienced a 50% or greater reduction in moderate to severe headache days, and there was no significant difference between placebo and fremanezumab after 12 weeks (26% versus 21%) or at month 1 (26% versus 19%), month 2 (33% versus 19%), or month 3 (28% versus 33%).

Adverse events occurred more often in the placebo group (81% versus 72%), and all were mild or moderate, with the exception of one that occurred in the placebo group. There were no deaths, and no meaningful changes in laboratory or clinical examinations.

Dr. Spierings is on the advisory board for Satsuma, is a speaker for Teva, Amgen, Novartis, Eli Lilly, Lundbeck, Biohaven, and AbbVie, and has been a clinical trial principal investigator for Teva, Novartis, Eli Lilly, Biohaven, and Satsuma. Dr. Tepper has been a consultant for Teva. Dr. Rapoport has consulted for Teva and has been a speaker for Teva.

A phase 2 study of the anti-calcitonin gene–related peptide (CGRP) antibody fremanezumab found no benefit of treatment in persistent posttraumatic headache. Anti-CGRP therapy had been predicted to be effective, given its history of improving other forms of headache, and preclinical studies had suggested that CGRP plays a role in late pain sensitization that can occur after mild brain injuries.

“There was a decrease in migraine headache days of moderate or severe intensity in both groups. But the difference between fremanezumab and placebo treatment was not statistically significant, either looking at that on a monthly basis or over the total 12 weeks of treatment,” Egilius L.H. Spierings, MD, PhD, said during his presentation of the results at the American Headache Society’s 2021 annual meeting. Dr. Spierings is medical director of the Boston Headache Institute.
 

Disappointing findings

“That’s sad. It’s just dreadful news,” Stewart J. Tepper, MD, professor of neurology at Geisel School of Medicine at Dartmouth, Hanover, N.H., said in an interview. Dr. Tepper was not involved in the study. The results suggest that CGRP mechanisms may not be relevant to persistent posttraumatic headache, but it could still play a role at onset. “We have to rethink this. Either it’s that chronic, persistent posttraumatic headache does not have a CGRP biology, or it’s that you have to get to them earlier [in the disease process],” he said.

The negative results were surprising, according to Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and former president of the International Headache Society. He noted that the study was small, and the researchers were unable to conduct subgroup analyses. “Posttraumatic headaches are usually broken down into those that phenotypically look like migraine, or phenotypically look like tension-type headache. It would have been nice to know if most of them had what clinically appears to be tension-type headache, and maybe that’s why they didn’t respond. Or did most of them have a migraine phenotype, and then it would be a little more surprising that they didn’t respond,” Dr. Rapoport said in an interview.

As a result, he believes that further studies might show that fremanezumab is an effective treatment for posttraumatic headache. “I would not give up on it. I expect that a larger study with better power, and a better idea of exactly what was wrong with the patients, might end up being a positive study,” he said.

Although most posttraumatic headaches resolve within weeks or months, some can linger or become chronic for years. Pain medication is often prescribed but should not be, according to Dr. Rapoport, because it can lead to medication overuse headache that worsens the problem. “So we badly need a good temporary preventive treatment. The thought of giving our newest, most effective preventive medications, with few adverse events, is a good one. It just didn’t seem to work in this fairly small and underpowered study,” he said.
 

The phase 2 trial

The trial included 87 patients with new-onset or significant worsening of headache following a minor traumatic brain injury or concussion, who were randomized to treatment with 675 mg subcutaneous fremanezumab once monthly, or placebo. The average elapsed time since the trauma was 8.1 years in the placebo group and 9.3 years in the fremanezumab arm. The average number of moderate to severe headache days was 18.5 days in the placebo group and 18.4 days in the fremanezumab group. The initial 12-week randomized period was followed by an open-label period in which patients on placebo received the study drug.

After 12 weeks of treatment, there was a greater decrease in moderate to severe headache days in the placebo arm, though the difference was not statistically significant (–5.1 versus –3.6 days; P = .1876). At 1 month, the two groups were similar (–4 days placebo versus –3.6 days fremanezumab), but there was a greater reduction in the placebo arm at 2 months (–6.7 versus –3.7 days) and 3 months (–7.21 versus –5.2 days).

A secondary endpoint was the proportion of patients who experienced a 50% or greater reduction in moderate to severe headache days, and there was no significant difference between placebo and fremanezumab after 12 weeks (26% versus 21%) or at month 1 (26% versus 19%), month 2 (33% versus 19%), or month 3 (28% versus 33%).

Adverse events occurred more often in the placebo group (81% versus 72%), and all were mild or moderate, with the exception of one that occurred in the placebo group. There were no deaths, and no meaningful changes in laboratory or clinical examinations.

Dr. Spierings is on the advisory board for Satsuma, is a speaker for Teva, Amgen, Novartis, Eli Lilly, Lundbeck, Biohaven, and AbbVie, and has been a clinical trial principal investigator for Teva, Novartis, Eli Lilly, Biohaven, and Satsuma. Dr. Tepper has been a consultant for Teva. Dr. Rapoport has consulted for Teva and has been a speaker for Teva.

A phase 2 study of the anti-calcitonin gene–related peptide (CGRP) antibody fremanezumab found no benefit of treatment in persistent posttraumatic headache. Anti-CGRP therapy had been predicted to be effective, given its history of improving other forms of headache, and preclinical studies had suggested that CGRP plays a role in late pain sensitization that can occur after mild brain injuries.

“There was a decrease in migraine headache days of moderate or severe intensity in both groups. But the difference between fremanezumab and placebo treatment was not statistically significant, either looking at that on a monthly basis or over the total 12 weeks of treatment,” Egilius L.H. Spierings, MD, PhD, said during his presentation of the results at the American Headache Society’s 2021 annual meeting. Dr. Spierings is medical director of the Boston Headache Institute.
 

Disappointing findings

“That’s sad. It’s just dreadful news,” Stewart J. Tepper, MD, professor of neurology at Geisel School of Medicine at Dartmouth, Hanover, N.H., said in an interview. Dr. Tepper was not involved in the study. The results suggest that CGRP mechanisms may not be relevant to persistent posttraumatic headache, but it could still play a role at onset. “We have to rethink this. Either it’s that chronic, persistent posttraumatic headache does not have a CGRP biology, or it’s that you have to get to them earlier [in the disease process],” he said.

The negative results were surprising, according to Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and former president of the International Headache Society. He noted that the study was small, and the researchers were unable to conduct subgroup analyses. “Posttraumatic headaches are usually broken down into those that phenotypically look like migraine, or phenotypically look like tension-type headache. It would have been nice to know if most of them had what clinically appears to be tension-type headache, and maybe that’s why they didn’t respond. Or did most of them have a migraine phenotype, and then it would be a little more surprising that they didn’t respond,” Dr. Rapoport said in an interview.

As a result, he believes that further studies might show that fremanezumab is an effective treatment for posttraumatic headache. “I would not give up on it. I expect that a larger study with better power, and a better idea of exactly what was wrong with the patients, might end up being a positive study,” he said.

Although most posttraumatic headaches resolve within weeks or months, some can linger or become chronic for years. Pain medication is often prescribed but should not be, according to Dr. Rapoport, because it can lead to medication overuse headache that worsens the problem. “So we badly need a good temporary preventive treatment. The thought of giving our newest, most effective preventive medications, with few adverse events, is a good one. It just didn’t seem to work in this fairly small and underpowered study,” he said.
 

The phase 2 trial

The trial included 87 patients with new-onset or significant worsening of headache following a minor traumatic brain injury or concussion, who were randomized to treatment with 675 mg subcutaneous fremanezumab once monthly, or placebo. The average elapsed time since the trauma was 8.1 years in the placebo group and 9.3 years in the fremanezumab arm. The average number of moderate to severe headache days was 18.5 days in the placebo group and 18.4 days in the fremanezumab group. The initial 12-week randomized period was followed by an open-label period in which patients on placebo received the study drug.

After 12 weeks of treatment, there was a greater decrease in moderate to severe headache days in the placebo arm, though the difference was not statistically significant (–5.1 versus –3.6 days; P = .1876). At 1 month, the two groups were similar (–4 days placebo versus –3.6 days fremanezumab), but there was a greater reduction in the placebo arm at 2 months (–6.7 versus –3.7 days) and 3 months (–7.21 versus –5.2 days).

A secondary endpoint was the proportion of patients who experienced a 50% or greater reduction in moderate to severe headache days, and there was no significant difference between placebo and fremanezumab after 12 weeks (26% versus 21%) or at month 1 (26% versus 19%), month 2 (33% versus 19%), or month 3 (28% versus 33%).

Adverse events occurred more often in the placebo group (81% versus 72%), and all were mild or moderate, with the exception of one that occurred in the placebo group. There were no deaths, and no meaningful changes in laboratory or clinical examinations.

Dr. Spierings is on the advisory board for Satsuma, is a speaker for Teva, Amgen, Novartis, Eli Lilly, Lundbeck, Biohaven, and AbbVie, and has been a clinical trial principal investigator for Teva, Novartis, Eli Lilly, Biohaven, and Satsuma. Dr. Tepper has been a consultant for Teva. Dr. Rapoport has consulted for Teva and has been a speaker for Teva.

Apparent migraines experienced by 19th century factory workers remain relevant to clinical medicine today. Those workers were employed in the manufacture of nitroglycerine, and many became patients of a physician who in 1880 described them as experiencing headache with nausea, vomiting, and walking lightly on their toes. A majority of patients were women.

When researchers in the 1950s worked out how to use nitroglycerine to trigger migraine-like headaches, the chemical became an important experimental tool, Peter Goadsby, MD, PhD, said during a talk on the translational importance of nitroglycerine in headache medicine at the American Headache Society’s 2021 annual meeting.

Some neurologists view nitroglycerine with skepticism, but that’s not necessarily warranted, said Dr. Goadsby. “To me, it’s underappreciated, but it has matured. If you were talking about this topic a decade ago, then the criticism would be that somehow that it’s not migraine, or it’s got nothing really to do with migraine,” he said in an interview.

But varying lines of clinical and experimental research have strengthened the case that nitroglycerine-induced migraine is largely indistinguishable from natural-onset migraine, and that studies that use it can provide important insights into patient management. “If I said to a colleague, ‘I’ve got this patient with headaches, and they’ve got nausea, and they’re sensitive to light. And if they move their head about, it’s worse,’ that sounds like migraine, and that’s what they’d say. The patients will tell you it’s the same, and they have the same premonitory symptoms. They respond to the same medicines,” said Dr. Goadsby.

The method is also one of the few available to study premonitory symptoms, since it is difficult to predict naturally-occurring migraines. Once the minimal dose of nitroglycerine dose to trigger an attack was worked out, researchers could use functional imaging to monitor what happens before and during the episode. To support this point, Dr. Goadsby cited a 2005 study in Brain by his own group. They used positron-emission tomography (PET) scans to conclude that lateralized brain dysfunction is associated with lateralized pain during migraine.

The premonitory stage is characterized by symptoms such as neck stiffness, cognitive impairment, mood alterations, and fatigue, as well as homeostatic symptoms such as sleepiness and polyuria. Other possible symptoms include photophobia, phonophobia, nausea, and cranial autonomic symptoms. These symptoms can be studied and established with the use of nitroglycerin trigger studies.

Dr. Goadsby pointed out that triggered episodes can also be used to test therapeutics. Calcitonin gene-related peptide receptor antagonists, 5-HT1F receptor agonists, and substance P/neurokinin 1 receptor antagonists have all been tested against nitroglycerine-induced migraines.

Other studies have used repeat exposures to nitroglycerine to better understand the effects of chronic migraines. Dr. Goadsby cited an example by researchers at the University of Illinois at Chicago led by Amynah Pradhan, PhD, which administered nitroglycerine repeatedly to mice and found that it led to acute mechanical hyperalgesia and basal hyperalgesia. The latter effect was dose dependent and persistent after nitroglycerine administration stopped. The phosphodiesterase inhibitor sildenafil, which can trigger migraines in humans, made the effect worse, suggesting that nitric oxide may be the mediator.

Apparent migraines experienced by 19th century factory workers remain relevant to clinical medicine today. Those workers were employed in the manufacture of nitroglycerine, and many became patients of a physician who in 1880 described them as experiencing headache with nausea, vomiting, and walking lightly on their toes. A majority of patients were women.

When researchers in the 1950s worked out how to use nitroglycerine to trigger migraine-like headaches, the chemical became an important experimental tool, Peter Goadsby, MD, PhD, said during a talk on the translational importance of nitroglycerine in headache medicine at the American Headache Society’s 2021 annual meeting.

Some neurologists view nitroglycerine with skepticism, but that’s not necessarily warranted, said Dr. Goadsby. “To me, it’s underappreciated, but it has matured. If you were talking about this topic a decade ago, then the criticism would be that somehow that it’s not migraine, or it’s got nothing really to do with migraine,” he said in an interview.

But varying lines of clinical and experimental research have strengthened the case that nitroglycerine-induced migraine is largely indistinguishable from natural-onset migraine, and that studies that use it can provide important insights into patient management. “If I said to a colleague, ‘I’ve got this patient with headaches, and they’ve got nausea, and they’re sensitive to light. And if they move their head about, it’s worse,’ that sounds like migraine, and that’s what they’d say. The patients will tell you it’s the same, and they have the same premonitory symptoms. They respond to the same medicines,” said Dr. Goadsby.

The method is also one of the few available to study premonitory symptoms, since it is difficult to predict naturally-occurring migraines. Once the minimal dose of nitroglycerine dose to trigger an attack was worked out, researchers could use functional imaging to monitor what happens before and during the episode. To support this point, Dr. Goadsby cited a 2005 study in Brain by his own group. They used positron-emission tomography (PET) scans to conclude that lateralized brain dysfunction is associated with lateralized pain during migraine.

The premonitory stage is characterized by symptoms such as neck stiffness, cognitive impairment, mood alterations, and fatigue, as well as homeostatic symptoms such as sleepiness and polyuria. Other possible symptoms include photophobia, phonophobia, nausea, and cranial autonomic symptoms. These symptoms can be studied and established with the use of nitroglycerin trigger studies.

Dr. Goadsby pointed out that triggered episodes can also be used to test therapeutics. Calcitonin gene-related peptide receptor antagonists, 5-HT1F receptor agonists, and substance P/neurokinin 1 receptor antagonists have all been tested against nitroglycerine-induced migraines.

Other studies have used repeat exposures to nitroglycerine to better understand the effects of chronic migraines. Dr. Goadsby cited an example by researchers at the University of Illinois at Chicago led by Amynah Pradhan, PhD, which administered nitroglycerine repeatedly to mice and found that it led to acute mechanical hyperalgesia and basal hyperalgesia. The latter effect was dose dependent and persistent after nitroglycerine administration stopped. The phosphodiesterase inhibitor sildenafil, which can trigger migraines in humans, made the effect worse, suggesting that nitric oxide may be the mediator.

Apparent migraines experienced by 19th century factory workers remain relevant to clinical medicine today. Those workers were employed in the manufacture of nitroglycerine, and many became patients of a physician who in 1880 described them as experiencing headache with nausea, vomiting, and walking lightly on their toes. A majority of patients were women.

When researchers in the 1950s worked out how to use nitroglycerine to trigger migraine-like headaches, the chemical became an important experimental tool, Peter Goadsby, MD, PhD, said during a talk on the translational importance of nitroglycerine in headache medicine at the American Headache Society’s 2021 annual meeting.

Some neurologists view nitroglycerine with skepticism, but that’s not necessarily warranted, said Dr. Goadsby. “To me, it’s underappreciated, but it has matured. If you were talking about this topic a decade ago, then the criticism would be that somehow that it’s not migraine, or it’s got nothing really to do with migraine,” he said in an interview.

But varying lines of clinical and experimental research have strengthened the case that nitroglycerine-induced migraine is largely indistinguishable from natural-onset migraine, and that studies that use it can provide important insights into patient management. “If I said to a colleague, ‘I’ve got this patient with headaches, and they’ve got nausea, and they’re sensitive to light. And if they move their head about, it’s worse,’ that sounds like migraine, and that’s what they’d say. The patients will tell you it’s the same, and they have the same premonitory symptoms. They respond to the same medicines,” said Dr. Goadsby.

The method is also one of the few available to study premonitory symptoms, since it is difficult to predict naturally-occurring migraines. Once the minimal dose of nitroglycerine dose to trigger an attack was worked out, researchers could use functional imaging to monitor what happens before and during the episode. To support this point, Dr. Goadsby cited a 2005 study in Brain by his own group. They used positron-emission tomography (PET) scans to conclude that lateralized brain dysfunction is associated with lateralized pain during migraine.

The premonitory stage is characterized by symptoms such as neck stiffness, cognitive impairment, mood alterations, and fatigue, as well as homeostatic symptoms such as sleepiness and polyuria. Other possible symptoms include photophobia, phonophobia, nausea, and cranial autonomic symptoms. These symptoms can be studied and established with the use of nitroglycerin trigger studies.

Dr. Goadsby pointed out that triggered episodes can also be used to test therapeutics. Calcitonin gene-related peptide receptor antagonists, 5-HT1F receptor agonists, and substance P/neurokinin 1 receptor antagonists have all been tested against nitroglycerine-induced migraines.

Other studies have used repeat exposures to nitroglycerine to better understand the effects of chronic migraines. Dr. Goadsby cited an example by researchers at the University of Illinois at Chicago led by Amynah Pradhan, PhD, which administered nitroglycerine repeatedly to mice and found that it led to acute mechanical hyperalgesia and basal hyperalgesia. The latter effect was dose dependent and persistent after nitroglycerine administration stopped. The phosphodiesterase inhibitor sildenafil, which can trigger migraines in humans, made the effect worse, suggesting that nitric oxide may be the mediator.

A novel 16-gene panel based on the biology of locoregional recurrence in early invasive breast cancer can both identify patients with a low risk of recurrence if they were to skip postsurgery radiation therapy, and predict which patients would be unlikely to benefit from adjuvant radiation, investigators reported.

Among 354 patients with stage I or II invasive estrogen receptor–positive (ER+), HER2-negative breast cancers who did not receive adjuvant systemic therapy, the genomic signature, dubbed POLAR (Profile for the Omission of Local Adjuvant Radiation) was prognostic for locoregional recurrence in patients who did not undergo radiation therapy, reported Martin Sjöström, MD, PhD, of the University of California, San Francisco, and colleagues.

They reported their findings in a poster presented during the American Society of Clinical Oncology (ASCO) annual meeting (Abstract 512).

“This is to our knowledge the first radiation-omission signature that is both prognostic and predictive: prognostic for outcomes in the absence of radiation, and predictive of benefits,” coauthor Corey Speers MD, PhD, of the University of Michigan, Ann Arbor, said in an interview.

The investigators conducted a retrospective analysis of data on patients enrolled in the SweBCG 91 RT trial, in which 1,187 patients with T1-2N0M0 breast cancer underwent a standardized radical sector resection and were then randomly assigned to either postoperative radiotherapy or no further treatment.

As the investigators reported in a long-term follow-up study presented in 2010 at the San Antonio Breast Cancer Symposium, the addition of postoperative radiation did not significantly affect overall survival, but was associated with a significant improvement in recurrence-free survival.

In the study presented at ASCO 2021, Dr. Sjöström and colleagues in Sweden, the United States, and Canada sought to determine whether they could identify a genomic signature that would identify women at very low risk for recurrence who could safely be spared from radiotherapy.

They focused on those patients in the study with ER+, HER2-negative tumors who did not receive adjuvant systemic therapy. The patients were divided into a training cohort of 243, and a validation cohort of 354 patients.

The investigators performed transcriptome-wide profiling of tumors, and identified both biological gene sets and individuals genes associated with locoregional recurrence among patients in the training set who did not receive radiotherapy.

The final POLAR genomic signature, containing 16 genes, was locked prior to testing in the validation cohort.

In a multivariable Cox model adjusting for age, grade, tumor size and luminal A vs. luminal B subtype, the POLAR gene set was prognostic for locoregional recurrence, with a hazard ratio (HR) of 1.7 (P < .001).

The 10-year locoregional recurrence rate for patients in the POLAR low-risk category who had not received radiation was 7%, and there was no significant benefit for POLAR low-risk patients who did receive radiation (HR 1.1, P = ns).

In contrast, patients classified as POLAR high risk who received radiotherapy had significantly lower risk for locoregional recurrence than high-risk patients who did not receive radiotherapy (HR 0.43, P = .0053).

Dr. Speers said that the POLAR signature appears to be unique in its ability to discriminate radiation-omission risk.

“At least looking in this cohort in the Swedish trial, none of other previously derived signatures – Mammaprint, ProSigna, Oncotype – were prognostic or predictive of locoregional recurrence events with radiation,” he said.

The investigators are currently exploring the POLAR signature in other clinical trials in which patients were randomized to receive radiation or no radiation.
 

­‘A true victory’

Invited discussant Benjamin D. Smith, MD, of the University of Texas MD Anderson Cancer Center in Houston, pointed out that in randomized clinical trials, approximately 60% of patients treated for early breast cancer did not experience recurrence in the absence of radiation, and that radiation prevented recurrence in about 30%, while about 10% experienced recurrence despite receiving radiation.

He said that the study by Dr. Sjöström and colleagues asks the question “can we use molecular factors to help identify patients who will not recur with lumpectomy alone without radiation therapy?”

The 60% of patients who will not experience recurrence in the absence of radiation can be categorized into two subpopulations: those with no residual malignant clonogens – the population included in this study by Dr. Sjöström and colleagues – and those with residual clonogens in the breast or elsewhere in the body that are sensitive to adjuvant endocrine therapy.

He said that the 7% 10-year risk of recurrence among patients in the POLAR low-risk group, who had neither radiation nor endocrine therapy, “is an exceptional outcome, which should be applauded, and I would point out that this risk of local recurrence of only 7% is at least in the same ballpark as the risk of recurrence that we accept every day when we treat early stage breast cancer patients with mastectomy alone, so this is a true victory.

“When we reflect on these provocative results from Dr. Sjöström and colleagues, it prompts in mind the question, could there be a group of patients with early breast cancer for whom a true ‘one-and-done’ strategy could be effective and safe?” Dr. Smith said.

Getting there will require a multidisciplinary, multimodality approach, involving imaging features of the primary tumor, clinical and pathologic features, and molecular information such as that provided by the POLAR genomic signature, he said.

The study was supported by PFS Genomics. Dr. Sjöström reported institutional funding from PFS Genomics. Dr. Speers disclosed stock and other ownership interests in the company, and he has applied for a patent on methods and genomic classifiers for prognosis of breast cancer and predicting benefit from adjuvant radiotherapy. Dr. Smith reported an equity interest in Oncora Medical, and an uncompensated relationship with the American Society for Radiation Oncology.

A novel 16-gene panel based on the biology of locoregional recurrence in early invasive breast cancer can both identify patients with a low risk of recurrence if they were to skip postsurgery radiation therapy, and predict which patients would be unlikely to benefit from adjuvant radiation, investigators reported.

Among 354 patients with stage I or II invasive estrogen receptor–positive (ER+), HER2-negative breast cancers who did not receive adjuvant systemic therapy, the genomic signature, dubbed POLAR (Profile for the Omission of Local Adjuvant Radiation) was prognostic for locoregional recurrence in patients who did not undergo radiation therapy, reported Martin Sjöström, MD, PhD, of the University of California, San Francisco, and colleagues.

They reported their findings in a poster presented during the American Society of Clinical Oncology (ASCO) annual meeting (Abstract 512).

“This is to our knowledge the first radiation-omission signature that is both prognostic and predictive: prognostic for outcomes in the absence of radiation, and predictive of benefits,” coauthor Corey Speers MD, PhD, of the University of Michigan, Ann Arbor, said in an interview.

The investigators conducted a retrospective analysis of data on patients enrolled in the SweBCG 91 RT trial, in which 1,187 patients with T1-2N0M0 breast cancer underwent a standardized radical sector resection and were then randomly assigned to either postoperative radiotherapy or no further treatment.

As the investigators reported in a long-term follow-up study presented in 2010 at the San Antonio Breast Cancer Symposium, the addition of postoperative radiation did not significantly affect overall survival, but was associated with a significant improvement in recurrence-free survival.

In the study presented at ASCO 2021, Dr. Sjöström and colleagues in Sweden, the United States, and Canada sought to determine whether they could identify a genomic signature that would identify women at very low risk for recurrence who could safely be spared from radiotherapy.

They focused on those patients in the study with ER+, HER2-negative tumors who did not receive adjuvant systemic therapy. The patients were divided into a training cohort of 243, and a validation cohort of 354 patients.

The investigators performed transcriptome-wide profiling of tumors, and identified both biological gene sets and individuals genes associated with locoregional recurrence among patients in the training set who did not receive radiotherapy.

The final POLAR genomic signature, containing 16 genes, was locked prior to testing in the validation cohort.

In a multivariable Cox model adjusting for age, grade, tumor size and luminal A vs. luminal B subtype, the POLAR gene set was prognostic for locoregional recurrence, with a hazard ratio (HR) of 1.7 (P < .001).

The 10-year locoregional recurrence rate for patients in the POLAR low-risk category who had not received radiation was 7%, and there was no significant benefit for POLAR low-risk patients who did receive radiation (HR 1.1, P = ns).

In contrast, patients classified as POLAR high risk who received radiotherapy had significantly lower risk for locoregional recurrence than high-risk patients who did not receive radiotherapy (HR 0.43, P = .0053).

Dr. Speers said that the POLAR signature appears to be unique in its ability to discriminate radiation-omission risk.

“At least looking in this cohort in the Swedish trial, none of other previously derived signatures – Mammaprint, ProSigna, Oncotype – were prognostic or predictive of locoregional recurrence events with radiation,” he said.

The investigators are currently exploring the POLAR signature in other clinical trials in which patients were randomized to receive radiation or no radiation.
 

­‘A true victory’

Invited discussant Benjamin D. Smith, MD, of the University of Texas MD Anderson Cancer Center in Houston, pointed out that in randomized clinical trials, approximately 60% of patients treated for early breast cancer did not experience recurrence in the absence of radiation, and that radiation prevented recurrence in about 30%, while about 10% experienced recurrence despite receiving radiation.

He said that the study by Dr. Sjöström and colleagues asks the question “can we use molecular factors to help identify patients who will not recur with lumpectomy alone without radiation therapy?”

The 60% of patients who will not experience recurrence in the absence of radiation can be categorized into two subpopulations: those with no residual malignant clonogens – the population included in this study by Dr. Sjöström and colleagues – and those with residual clonogens in the breast or elsewhere in the body that are sensitive to adjuvant endocrine therapy.

He said that the 7% 10-year risk of recurrence among patients in the POLAR low-risk group, who had neither radiation nor endocrine therapy, “is an exceptional outcome, which should be applauded, and I would point out that this risk of local recurrence of only 7% is at least in the same ballpark as the risk of recurrence that we accept every day when we treat early stage breast cancer patients with mastectomy alone, so this is a true victory.

“When we reflect on these provocative results from Dr. Sjöström and colleagues, it prompts in mind the question, could there be a group of patients with early breast cancer for whom a true ‘one-and-done’ strategy could be effective and safe?” Dr. Smith said.

Getting there will require a multidisciplinary, multimodality approach, involving imaging features of the primary tumor, clinical and pathologic features, and molecular information such as that provided by the POLAR genomic signature, he said.

The study was supported by PFS Genomics. Dr. Sjöström reported institutional funding from PFS Genomics. Dr. Speers disclosed stock and other ownership interests in the company, and he has applied for a patent on methods and genomic classifiers for prognosis of breast cancer and predicting benefit from adjuvant radiotherapy. Dr. Smith reported an equity interest in Oncora Medical, and an uncompensated relationship with the American Society for Radiation Oncology.

A novel 16-gene panel based on the biology of locoregional recurrence in early invasive breast cancer can both identify patients with a low risk of recurrence if they were to skip postsurgery radiation therapy, and predict which patients would be unlikely to benefit from adjuvant radiation, investigators reported.

Among 354 patients with stage I or II invasive estrogen receptor–positive (ER+), HER2-negative breast cancers who did not receive adjuvant systemic therapy, the genomic signature, dubbed POLAR (Profile for the Omission of Local Adjuvant Radiation) was prognostic for locoregional recurrence in patients who did not undergo radiation therapy, reported Martin Sjöström, MD, PhD, of the University of California, San Francisco, and colleagues.

They reported their findings in a poster presented during the American Society of Clinical Oncology (ASCO) annual meeting (Abstract 512).

“This is to our knowledge the first radiation-omission signature that is both prognostic and predictive: prognostic for outcomes in the absence of radiation, and predictive of benefits,” coauthor Corey Speers MD, PhD, of the University of Michigan, Ann Arbor, said in an interview.

The investigators conducted a retrospective analysis of data on patients enrolled in the SweBCG 91 RT trial, in which 1,187 patients with T1-2N0M0 breast cancer underwent a standardized radical sector resection and were then randomly assigned to either postoperative radiotherapy or no further treatment.

As the investigators reported in a long-term follow-up study presented in 2010 at the San Antonio Breast Cancer Symposium, the addition of postoperative radiation did not significantly affect overall survival, but was associated with a significant improvement in recurrence-free survival.

In the study presented at ASCO 2021, Dr. Sjöström and colleagues in Sweden, the United States, and Canada sought to determine whether they could identify a genomic signature that would identify women at very low risk for recurrence who could safely be spared from radiotherapy.

They focused on those patients in the study with ER+, HER2-negative tumors who did not receive adjuvant systemic therapy. The patients were divided into a training cohort of 243, and a validation cohort of 354 patients.

The investigators performed transcriptome-wide profiling of tumors, and identified both biological gene sets and individuals genes associated with locoregional recurrence among patients in the training set who did not receive radiotherapy.

The final POLAR genomic signature, containing 16 genes, was locked prior to testing in the validation cohort.

In a multivariable Cox model adjusting for age, grade, tumor size and luminal A vs. luminal B subtype, the POLAR gene set was prognostic for locoregional recurrence, with a hazard ratio (HR) of 1.7 (P < .001).

The 10-year locoregional recurrence rate for patients in the POLAR low-risk category who had not received radiation was 7%, and there was no significant benefit for POLAR low-risk patients who did receive radiation (HR 1.1, P = ns).

In contrast, patients classified as POLAR high risk who received radiotherapy had significantly lower risk for locoregional recurrence than high-risk patients who did not receive radiotherapy (HR 0.43, P = .0053).

Dr. Speers said that the POLAR signature appears to be unique in its ability to discriminate radiation-omission risk.

“At least looking in this cohort in the Swedish trial, none of other previously derived signatures – Mammaprint, ProSigna, Oncotype – were prognostic or predictive of locoregional recurrence events with radiation,” he said.

The investigators are currently exploring the POLAR signature in other clinical trials in which patients were randomized to receive radiation or no radiation.
 

­‘A true victory’

Invited discussant Benjamin D. Smith, MD, of the University of Texas MD Anderson Cancer Center in Houston, pointed out that in randomized clinical trials, approximately 60% of patients treated for early breast cancer did not experience recurrence in the absence of radiation, and that radiation prevented recurrence in about 30%, while about 10% experienced recurrence despite receiving radiation.

He said that the study by Dr. Sjöström and colleagues asks the question “can we use molecular factors to help identify patients who will not recur with lumpectomy alone without radiation therapy?”

The 60% of patients who will not experience recurrence in the absence of radiation can be categorized into two subpopulations: those with no residual malignant clonogens – the population included in this study by Dr. Sjöström and colleagues – and those with residual clonogens in the breast or elsewhere in the body that are sensitive to adjuvant endocrine therapy.

He said that the 7% 10-year risk of recurrence among patients in the POLAR low-risk group, who had neither radiation nor endocrine therapy, “is an exceptional outcome, which should be applauded, and I would point out that this risk of local recurrence of only 7% is at least in the same ballpark as the risk of recurrence that we accept every day when we treat early stage breast cancer patients with mastectomy alone, so this is a true victory.

“When we reflect on these provocative results from Dr. Sjöström and colleagues, it prompts in mind the question, could there be a group of patients with early breast cancer for whom a true ‘one-and-done’ strategy could be effective and safe?” Dr. Smith said.

Getting there will require a multidisciplinary, multimodality approach, involving imaging features of the primary tumor, clinical and pathologic features, and molecular information such as that provided by the POLAR genomic signature, he said.

The study was supported by PFS Genomics. Dr. Sjöström reported institutional funding from PFS Genomics. Dr. Speers disclosed stock and other ownership interests in the company, and he has applied for a patent on methods and genomic classifiers for prognosis of breast cancer and predicting benefit from adjuvant radiotherapy. Dr. Smith reported an equity interest in Oncora Medical, and an uncompensated relationship with the American Society for Radiation Oncology.

Background: Accurate identification of frail older patients at hospital admission may help target interventions; however, the extent to which risk prediction tools such as the frailty index can be utilized in the acute setting remains unclear.

Study design: Single-center prospective cohort study, during April 2015–January 2017.

Dr. Hu is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.

Background: Accurate identification of frail older patients at hospital admission may help target interventions; however, the extent to which risk prediction tools such as the frailty index can be utilized in the acute setting remains unclear.

Study design: Single-center prospective cohort study, during April 2015–January 2017.

Dr. Hu is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.

Background: Accurate identification of frail older patients at hospital admission may help target interventions; however, the extent to which risk prediction tools such as the frailty index can be utilized in the acute setting remains unclear.

Study design: Single-center prospective cohort study, during April 2015–January 2017.

Dr. Hu is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.

For women with HER2-positive early breast cancer treated with an anthracycline-based regimen followed by trastuzumab (Herceptin), concurrent therapy with the angiotensin-converting enzyme (ACE) inhibitor lisinopril can help to prevent a decline in left-ventricular ejection fraction (LVEF) below 50%, investigators in a community-based study found.

Among 424 women with HER2-positive early-stage breast cancer, the rate of LVEF decline to below 50% was 21.4% among patients randomized to receive an anthracycline-based regimen, compared with 4.1% for patients who were treated with a non–anthracycline-based regimen.

Among patients in the anthracycline arm, treatment with lisinopril, but not carvedilol or placebo, was associated with significant protection against LVEF decline, reported Pamela N. Munster, MD, of the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco.

“The findings of this study suggested that the drop in left ventricular ejection fraction to below 50% or to below normal was much larger than previously reported in the anthracycline group,” she said in a video presentation during a poster discussion session at the American Society of Clinical Oncology annual meeting. (Abstract 509).

Although HER2 inhibition is a highly effective treatment strategy for patients with HER2-positive tumors, trastuzumab-associated decline in LVEF and clinical heart failure can result in treatment interruption or discontinuation of therapy, the authors noted.

They conducted the prospective randomized trial to see whether trastuzumab-associated cardiotoxicity could be mitigated by concurrent use of either an ACE inhibitor or beta-blocker.

They enrolled women with early HER2-positive breast cancer from 127 community-based oncology centers.

The patients were randomly assigned to receive either an anthracycline- or non–anthracycline-containing regimen, followed by a year of trastuzumab, and were then randomized again to receive either lisinopril, carvedilol, or placebo concurrently with trastuzumab.

The patients were assessed for cardiotoxicity every 12 weeks with a multiple-gated acquisition (MUGA) scan and echocardiogram. Cardiotoxicity was defined as an absolute decrease in LVEF of 10% or more, or at least 5% decrease in LVEF below 50% at baseline.
 

Small LVEF declines in all

The investigators observed that all patients in the study experienced a small but not clinically relevant decrease in LVEF during trastuzumab therapy, and that this decline was not significantly ameliorated by any of the interventions.

However, as noted before, among patients assigned to anthracycline-based regimens the rate of decline to LVEF below 50% was 21.4%, compared with 4.1 for patients assigned to non–anthracycline regimens.

LVEF declines of at least 10% occurred in 5.5% of patients who received anthracyclines, and in 14.4% of those who received a non-anthracycline regimen.

Among patients who received anthracycline, only 10.8% randomized to receive lisinopril prophylaxis experienced a decline in LVEF, compared with 30.5% assigned to placebo (P = .045).

“In contrast, while carvedilol showed a numerical prevention of LVEF below 50% to 22.8%, this was not statistically significant,” Dr. Munster said.

Decreases in LVEF of 10% or greater within the normal LVEF range were similar in both chemotherapy arms and were not affected by either lisinopril or carvedilol.

“Lisinopril was well tolerated in this group, even in patients without hypertension,” she said.

“In women treated in a community-based environment who could benefit from anthracyclines or where anthracyclines are indicated, one should anticipate the decrease in left ventricular ejection fraction to below normal to be larger than is reported by other groups. However, this could be prevented by lisinopril,” she concluded.
 

Low numbers overall

Invited discussant Fatima Cardoso, MD, of Champalimaud Clinical Center in Lisbon, noted that the overall number of cardiotoxicity events and the rate of important decreases in LVEF were comparatively low.

She also pointed out that the findings are in line with another recent analysis of the same cohort by the same authors, although in the earlier analysis the investigators found that the effect on cardiotoxicity-free survival was good with both agents compared with placebo, but slightly better with carvedilol (hazard ratio 0.49, P = .009) than with lisinopril (HR 0.53, P = .015).

“Lisinopril has the most important effect regarding preventing decrease of LVEF below 50%. When we look at the curves of LVEF drops above 10%, carvedilol seems to have a slightly bigger effect,” she said.

The trial was cosponsored by the SunCoast Community Clinical Oncology Programs Research Base at University of South Florida, Tampa, and by the National Cancer Institute. Dr. Munster disclosed leadership positions, stock ownership, and consulting or advisory roles with several companies. Dr. Cardoso disclosed consulting or advisory roles and travel support from multiple companies.

For women with HER2-positive early breast cancer treated with an anthracycline-based regimen followed by trastuzumab (Herceptin), concurrent therapy with the angiotensin-converting enzyme (ACE) inhibitor lisinopril can help to prevent a decline in left-ventricular ejection fraction (LVEF) below 50%, investigators in a community-based study found.

Among 424 women with HER2-positive early-stage breast cancer, the rate of LVEF decline to below 50% was 21.4% among patients randomized to receive an anthracycline-based regimen, compared with 4.1% for patients who were treated with a non–anthracycline-based regimen.

Among patients in the anthracycline arm, treatment with lisinopril, but not carvedilol or placebo, was associated with significant protection against LVEF decline, reported Pamela N. Munster, MD, of the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco.

“The findings of this study suggested that the drop in left ventricular ejection fraction to below 50% or to below normal was much larger than previously reported in the anthracycline group,” she said in a video presentation during a poster discussion session at the American Society of Clinical Oncology annual meeting. (Abstract 509).

Although HER2 inhibition is a highly effective treatment strategy for patients with HER2-positive tumors, trastuzumab-associated decline in LVEF and clinical heart failure can result in treatment interruption or discontinuation of therapy, the authors noted.

They conducted the prospective randomized trial to see whether trastuzumab-associated cardiotoxicity could be mitigated by concurrent use of either an ACE inhibitor or beta-blocker.

They enrolled women with early HER2-positive breast cancer from 127 community-based oncology centers.

The patients were randomly assigned to receive either an anthracycline- or non–anthracycline-containing regimen, followed by a year of trastuzumab, and were then randomized again to receive either lisinopril, carvedilol, or placebo concurrently with trastuzumab.

The patients were assessed for cardiotoxicity every 12 weeks with a multiple-gated acquisition (MUGA) scan and echocardiogram. Cardiotoxicity was defined as an absolute decrease in LVEF of 10% or more, or at least 5% decrease in LVEF below 50% at baseline.
 

Small LVEF declines in all

The investigators observed that all patients in the study experienced a small but not clinically relevant decrease in LVEF during trastuzumab therapy, and that this decline was not significantly ameliorated by any of the interventions.

However, as noted before, among patients assigned to anthracycline-based regimens the rate of decline to LVEF below 50% was 21.4%, compared with 4.1 for patients assigned to non–anthracycline regimens.

LVEF declines of at least 10% occurred in 5.5% of patients who received anthracyclines, and in 14.4% of those who received a non-anthracycline regimen.

Among patients who received anthracycline, only 10.8% randomized to receive lisinopril prophylaxis experienced a decline in LVEF, compared with 30.5% assigned to placebo (P = .045).

“In contrast, while carvedilol showed a numerical prevention of LVEF below 50% to 22.8%, this was not statistically significant,” Dr. Munster said.

Decreases in LVEF of 10% or greater within the normal LVEF range were similar in both chemotherapy arms and were not affected by either lisinopril or carvedilol.

“Lisinopril was well tolerated in this group, even in patients without hypertension,” she said.

“In women treated in a community-based environment who could benefit from anthracyclines or where anthracyclines are indicated, one should anticipate the decrease in left ventricular ejection fraction to below normal to be larger than is reported by other groups. However, this could be prevented by lisinopril,” she concluded.
 

Low numbers overall

Invited discussant Fatima Cardoso, MD, of Champalimaud Clinical Center in Lisbon, noted that the overall number of cardiotoxicity events and the rate of important decreases in LVEF were comparatively low.

She also pointed out that the findings are in line with another recent analysis of the same cohort by the same authors, although in the earlier analysis the investigators found that the effect on cardiotoxicity-free survival was good with both agents compared with placebo, but slightly better with carvedilol (hazard ratio 0.49, P = .009) than with lisinopril (HR 0.53, P = .015).

“Lisinopril has the most important effect regarding preventing decrease of LVEF below 50%. When we look at the curves of LVEF drops above 10%, carvedilol seems to have a slightly bigger effect,” she said.

The trial was cosponsored by the SunCoast Community Clinical Oncology Programs Research Base at University of South Florida, Tampa, and by the National Cancer Institute. Dr. Munster disclosed leadership positions, stock ownership, and consulting or advisory roles with several companies. Dr. Cardoso disclosed consulting or advisory roles and travel support from multiple companies.

For women with HER2-positive early breast cancer treated with an anthracycline-based regimen followed by trastuzumab (Herceptin), concurrent therapy with the angiotensin-converting enzyme (ACE) inhibitor lisinopril can help to prevent a decline in left-ventricular ejection fraction (LVEF) below 50%, investigators in a community-based study found.

Among 424 women with HER2-positive early-stage breast cancer, the rate of LVEF decline to below 50% was 21.4% among patients randomized to receive an anthracycline-based regimen, compared with 4.1% for patients who were treated with a non–anthracycline-based regimen.

Among patients in the anthracycline arm, treatment with lisinopril, but not carvedilol or placebo, was associated with significant protection against LVEF decline, reported Pamela N. Munster, MD, of the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco.

“The findings of this study suggested that the drop in left ventricular ejection fraction to below 50% or to below normal was much larger than previously reported in the anthracycline group,” she said in a video presentation during a poster discussion session at the American Society of Clinical Oncology annual meeting. (Abstract 509).

Although HER2 inhibition is a highly effective treatment strategy for patients with HER2-positive tumors, trastuzumab-associated decline in LVEF and clinical heart failure can result in treatment interruption or discontinuation of therapy, the authors noted.

They conducted the prospective randomized trial to see whether trastuzumab-associated cardiotoxicity could be mitigated by concurrent use of either an ACE inhibitor or beta-blocker.

They enrolled women with early HER2-positive breast cancer from 127 community-based oncology centers.

The patients were randomly assigned to receive either an anthracycline- or non–anthracycline-containing regimen, followed by a year of trastuzumab, and were then randomized again to receive either lisinopril, carvedilol, or placebo concurrently with trastuzumab.

The patients were assessed for cardiotoxicity every 12 weeks with a multiple-gated acquisition (MUGA) scan and echocardiogram. Cardiotoxicity was defined as an absolute decrease in LVEF of 10% or more, or at least 5% decrease in LVEF below 50% at baseline.
 

Small LVEF declines in all

The investigators observed that all patients in the study experienced a small but not clinically relevant decrease in LVEF during trastuzumab therapy, and that this decline was not significantly ameliorated by any of the interventions.

However, as noted before, among patients assigned to anthracycline-based regimens the rate of decline to LVEF below 50% was 21.4%, compared with 4.1 for patients assigned to non–anthracycline regimens.

LVEF declines of at least 10% occurred in 5.5% of patients who received anthracyclines, and in 14.4% of those who received a non-anthracycline regimen.

Among patients who received anthracycline, only 10.8% randomized to receive lisinopril prophylaxis experienced a decline in LVEF, compared with 30.5% assigned to placebo (P = .045).

“In contrast, while carvedilol showed a numerical prevention of LVEF below 50% to 22.8%, this was not statistically significant,” Dr. Munster said.

Decreases in LVEF of 10% or greater within the normal LVEF range were similar in both chemotherapy arms and were not affected by either lisinopril or carvedilol.

“Lisinopril was well tolerated in this group, even in patients without hypertension,” she said.

“In women treated in a community-based environment who could benefit from anthracyclines or where anthracyclines are indicated, one should anticipate the decrease in left ventricular ejection fraction to below normal to be larger than is reported by other groups. However, this could be prevented by lisinopril,” she concluded.
 

Low numbers overall

Invited discussant Fatima Cardoso, MD, of Champalimaud Clinical Center in Lisbon, noted that the overall number of cardiotoxicity events and the rate of important decreases in LVEF were comparatively low.

She also pointed out that the findings are in line with another recent analysis of the same cohort by the same authors, although in the earlier analysis the investigators found that the effect on cardiotoxicity-free survival was good with both agents compared with placebo, but slightly better with carvedilol (hazard ratio 0.49, P = .009) than with lisinopril (HR 0.53, P = .015).

“Lisinopril has the most important effect regarding preventing decrease of LVEF below 50%. When we look at the curves of LVEF drops above 10%, carvedilol seems to have a slightly bigger effect,” she said.

The trial was cosponsored by the SunCoast Community Clinical Oncology Programs Research Base at University of South Florida, Tampa, and by the National Cancer Institute. Dr. Munster disclosed leadership positions, stock ownership, and consulting or advisory roles with several companies. Dr. Cardoso disclosed consulting or advisory roles and travel support from multiple companies.

Key clinical point: Hepatocellular carcinoma patients with intermediate or advanced disease experienced significantly improved outcomes when treated with transarterial chemoembolization (TACE) plus sorafenib vs. TACE only.

Major finding: Patients treated with TACE plus sorafenib showed a significant increase in average progression-free survival and overall survival compared to those treated with TACE only (21 months vs. 12 months and 32 months vs. 21 months, respectively).

Study details: The data come from a retrospective review of 85 adults with intermediate or advanced HCC who were treated with transarterial chemoembolization (TACE) alone or with sorafenib.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.  

Source: Zou X et al. Cancer Manag Res. 2021 May 18. doi: 10.2147/CMAR.S304591. 

Key clinical point: Hepatocellular carcinoma patients with intermediate or advanced disease experienced significantly improved outcomes when treated with transarterial chemoembolization (TACE) plus sorafenib vs. TACE only.

Major finding: Patients treated with TACE plus sorafenib showed a significant increase in average progression-free survival and overall survival compared to those treated with TACE only (21 months vs. 12 months and 32 months vs. 21 months, respectively).

Study details: The data come from a retrospective review of 85 adults with intermediate or advanced HCC who were treated with transarterial chemoembolization (TACE) alone or with sorafenib.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.  

Source: Zou X et al. Cancer Manag Res. 2021 May 18. doi: 10.2147/CMAR.S304591. 

Key clinical point: Hepatocellular carcinoma patients with intermediate or advanced disease experienced significantly improved outcomes when treated with transarterial chemoembolization (TACE) plus sorafenib vs. TACE only.

Major finding: Patients treated with TACE plus sorafenib showed a significant increase in average progression-free survival and overall survival compared to those treated with TACE only (21 months vs. 12 months and 32 months vs. 21 months, respectively).

Study details: The data come from a retrospective review of 85 adults with intermediate or advanced HCC who were treated with transarterial chemoembolization (TACE) alone or with sorafenib.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.  

Source: Zou X et al. Cancer Manag Res. 2021 May 18. doi: 10.2147/CMAR.S304591.