Immuno-oncology

MADRID – Although pembrolizumab (Keytruda) was associated with a 19% reduction in the risk of death compared with the standard of care in patients with relapsed or metastatic head and neck squamous cell carcinoma (HNSCC) in the KEYNOTE 040 trial, the immune checkpoint inhibitor just missed meeting its primary efficacy endpoint of an improvement in overall survival.

The fault may lie in the confounding of overall survival results when patients who were initially assigned to standard of care were crossed over to subsequent therapy with a checkpoint inhibitor after the study ended, said lead investigator Ezra Cohen, MD, of Moores Cancer Center at UC San Diego Health Sciences in La Jolla, Calif.

“This was a trial that clearly did not meet its primary endpoint, but was felt to confer some benefit – at least in the opinion of this investigator – to pembrolizumab vs. standard of care,” he said at the European Society for Medical Oncology Congress.

Some math required

Dr. Cohen explained that the statistical design of the trial involved a multiplicity strategy using a family-wise alpha strictly controlled at 0.025. The alpha was allocated in a stepwise fashion. The study hypothesis was that pembrolizumab would have an overall survival (OS) advantage with a one-side alpha, and if that was met, OS would then be looked at in specific cohorts according to expression of the PD ligand 1 (PD-L1) on cells, followed by evaluation of objective response rates and progression-free survival in each subgroup.

The final analysis was to be performed after 380 OS events had occurred among 495 randomized patients. The prespecified efficacy boundary for OS in the intention-to-treat (ITT) population was .0175, translating into a hazard ratio (HR) of 0.80.

Median OS in the ITT population was 8.4 months for the pembrolizumab arm, compared with 7.1 months for the standard-of-care arm. This translated into an HR of 0.81 (P = .0204), which do not reach the aforementioned efficacy boundary.

Rates of 1-year overall survival were 37% in the experimental arm, vs. 27% in the standard-of-care arm.

“When one looks at the biomarker-specific cohorts, we can see that these differences are further exaggerated in favor of pembrolizumab, Dr. Cohen said.

An analysis stratified by patients with PD-L1 expression on 1% or more of cells vs. less than 1% showed median overall OS of 8.7 months for those with higher levels of expression, vs. 7.1 months for expression levels below 1% (HR 0.75, P = .0078).

Similarly, an analysis comparing patients with a tumor proportion score (TPS; expression of PD-L1 in the membranes of 50% or more of tumor cells) with patients whose tumors had lower TPS levels showed a median OS of 11.6 months with pembrolizumab, vs. 7.9 months with standard of care (HR 0.54, P = .0017).

Objective response rates were also significantly higher with pembrolizumab in the patients with higher levels of both overall PD-L1 expression (17.3% vs. 9.9% with standard care), and in patients with 50% or more of tumor cells expressing membrane PD-L1 (26.6% vs. 65%, P = .0009).

In an exploratory analysis, the investigators also found that among patients in the standard of care arm who went on to receive a checkpoint inhibitor as subsequent therapy, the median OS was 20.1 months, compared with 9.8 months for patients who received other subsequent therapies, and 4.8 months for those who did not receive subsequent therapy, suggesting that crossover to a checkpoint inhibitor may have diluted overall survival differences between the trial arms, Dr. Cohen said.

Treatment-related adverse events of any grade were more frequent in the standard of care arm, except for hypothyroidism, which was substantially more frequent with pembrolizumab. The incidence of immune-mediated adverse events other than hypothyroidism was generally similar between the treatment arms.

“I think pembrolizumab, despite not meeting the primary endpoint of overall survival, showed evidence of activity and a [good] safety profile. So I think this study is borderline possible, since there is a 19% reduction in the risk of death, with a hazard ratio borderline to the statistical hypothesis that was initially planned,” said invited discussant Sandrine Faivre, MD, PhD, of Bichat-Beaujon University Hospitals in Paris.

MADRID – Although pembrolizumab (Keytruda) was associated with a 19% reduction in the risk of death compared with the standard of care in patients with relapsed or metastatic head and neck squamous cell carcinoma (HNSCC) in the KEYNOTE 040 trial, the immune checkpoint inhibitor just missed meeting its primary efficacy endpoint of an improvement in overall survival.

The fault may lie in the confounding of overall survival results when patients who were initially assigned to standard of care were crossed over to subsequent therapy with a checkpoint inhibitor after the study ended, said lead investigator Ezra Cohen, MD, of Moores Cancer Center at UC San Diego Health Sciences in La Jolla, Calif.

“This was a trial that clearly did not meet its primary endpoint, but was felt to confer some benefit – at least in the opinion of this investigator – to pembrolizumab vs. standard of care,” he said at the European Society for Medical Oncology Congress.

Some math required

Dr. Cohen explained that the statistical design of the trial involved a multiplicity strategy using a family-wise alpha strictly controlled at 0.025. The alpha was allocated in a stepwise fashion. The study hypothesis was that pembrolizumab would have an overall survival (OS) advantage with a one-side alpha, and if that was met, OS would then be looked at in specific cohorts according to expression of the PD ligand 1 (PD-L1) on cells, followed by evaluation of objective response rates and progression-free survival in each subgroup.

The final analysis was to be performed after 380 OS events had occurred among 495 randomized patients. The prespecified efficacy boundary for OS in the intention-to-treat (ITT) population was .0175, translating into a hazard ratio (HR) of 0.80.

Median OS in the ITT population was 8.4 months for the pembrolizumab arm, compared with 7.1 months for the standard-of-care arm. This translated into an HR of 0.81 (P = .0204), which do not reach the aforementioned efficacy boundary.

Rates of 1-year overall survival were 37% in the experimental arm, vs. 27% in the standard-of-care arm.

“When one looks at the biomarker-specific cohorts, we can see that these differences are further exaggerated in favor of pembrolizumab, Dr. Cohen said.

An analysis stratified by patients with PD-L1 expression on 1% or more of cells vs. less than 1% showed median overall OS of 8.7 months for those with higher levels of expression, vs. 7.1 months for expression levels below 1% (HR 0.75, P = .0078).

Similarly, an analysis comparing patients with a tumor proportion score (TPS; expression of PD-L1 in the membranes of 50% or more of tumor cells) with patients whose tumors had lower TPS levels showed a median OS of 11.6 months with pembrolizumab, vs. 7.9 months with standard of care (HR 0.54, P = .0017).

Objective response rates were also significantly higher with pembrolizumab in the patients with higher levels of both overall PD-L1 expression (17.3% vs. 9.9% with standard care), and in patients with 50% or more of tumor cells expressing membrane PD-L1 (26.6% vs. 65%, P = .0009).

In an exploratory analysis, the investigators also found that among patients in the standard of care arm who went on to receive a checkpoint inhibitor as subsequent therapy, the median OS was 20.1 months, compared with 9.8 months for patients who received other subsequent therapies, and 4.8 months for those who did not receive subsequent therapy, suggesting that crossover to a checkpoint inhibitor may have diluted overall survival differences between the trial arms, Dr. Cohen said.

Treatment-related adverse events of any grade were more frequent in the standard of care arm, except for hypothyroidism, which was substantially more frequent with pembrolizumab. The incidence of immune-mediated adverse events other than hypothyroidism was generally similar between the treatment arms.

“I think pembrolizumab, despite not meeting the primary endpoint of overall survival, showed evidence of activity and a [good] safety profile. So I think this study is borderline possible, since there is a 19% reduction in the risk of death, with a hazard ratio borderline to the statistical hypothesis that was initially planned,” said invited discussant Sandrine Faivre, MD, PhD, of Bichat-Beaujon University Hospitals in Paris.

MADRID – Although pembrolizumab (Keytruda) was associated with a 19% reduction in the risk of death compared with the standard of care in patients with relapsed or metastatic head and neck squamous cell carcinoma (HNSCC) in the KEYNOTE 040 trial, the immune checkpoint inhibitor just missed meeting its primary efficacy endpoint of an improvement in overall survival.

The fault may lie in the confounding of overall survival results when patients who were initially assigned to standard of care were crossed over to subsequent therapy with a checkpoint inhibitor after the study ended, said lead investigator Ezra Cohen, MD, of Moores Cancer Center at UC San Diego Health Sciences in La Jolla, Calif.

“This was a trial that clearly did not meet its primary endpoint, but was felt to confer some benefit – at least in the opinion of this investigator – to pembrolizumab vs. standard of care,” he said at the European Society for Medical Oncology Congress.

Some math required

Dr. Cohen explained that the statistical design of the trial involved a multiplicity strategy using a family-wise alpha strictly controlled at 0.025. The alpha was allocated in a stepwise fashion. The study hypothesis was that pembrolizumab would have an overall survival (OS) advantage with a one-side alpha, and if that was met, OS would then be looked at in specific cohorts according to expression of the PD ligand 1 (PD-L1) on cells, followed by evaluation of objective response rates and progression-free survival in each subgroup.

The final analysis was to be performed after 380 OS events had occurred among 495 randomized patients. The prespecified efficacy boundary for OS in the intention-to-treat (ITT) population was .0175, translating into a hazard ratio (HR) of 0.80.

Median OS in the ITT population was 8.4 months for the pembrolizumab arm, compared with 7.1 months for the standard-of-care arm. This translated into an HR of 0.81 (P = .0204), which do not reach the aforementioned efficacy boundary.

Rates of 1-year overall survival were 37% in the experimental arm, vs. 27% in the standard-of-care arm.

“When one looks at the biomarker-specific cohorts, we can see that these differences are further exaggerated in favor of pembrolizumab, Dr. Cohen said.

An analysis stratified by patients with PD-L1 expression on 1% or more of cells vs. less than 1% showed median overall OS of 8.7 months for those with higher levels of expression, vs. 7.1 months for expression levels below 1% (HR 0.75, P = .0078).

Similarly, an analysis comparing patients with a tumor proportion score (TPS; expression of PD-L1 in the membranes of 50% or more of tumor cells) with patients whose tumors had lower TPS levels showed a median OS of 11.6 months with pembrolizumab, vs. 7.9 months with standard of care (HR 0.54, P = .0017).

Objective response rates were also significantly higher with pembrolizumab in the patients with higher levels of both overall PD-L1 expression (17.3% vs. 9.9% with standard care), and in patients with 50% or more of tumor cells expressing membrane PD-L1 (26.6% vs. 65%, P = .0009).

In an exploratory analysis, the investigators also found that among patients in the standard of care arm who went on to receive a checkpoint inhibitor as subsequent therapy, the median OS was 20.1 months, compared with 9.8 months for patients who received other subsequent therapies, and 4.8 months for those who did not receive subsequent therapy, suggesting that crossover to a checkpoint inhibitor may have diluted overall survival differences between the trial arms, Dr. Cohen said.

Treatment-related adverse events of any grade were more frequent in the standard of care arm, except for hypothyroidism, which was substantially more frequent with pembrolizumab. The incidence of immune-mediated adverse events other than hypothyroidism was generally similar between the treatment arms.

“I think pembrolizumab, despite not meeting the primary endpoint of overall survival, showed evidence of activity and a [good] safety profile. So I think this study is borderline possible, since there is a 19% reduction in the risk of death, with a hazard ratio borderline to the statistical hypothesis that was initially planned,” said invited discussant Sandrine Faivre, MD, PhD, of Bichat-Beaujon University Hospitals in Paris.

Outrage over the high cost of cancer care has focused on skyrocketing drug prices, including the $475,000 price tag for the country’s first gene therapy, Novartis’ Kymriah (tisagenlecleucel), a leukemia treatment approved in August.

But the total costs of tisagenlecleucel and the 21 similar drugs in development – known as CAR T-cell therapies – will be far higher than many have imagined, reaching $1 million or more per patient, according to leading cancer experts. The next CAR T-cell drug could be approved as soon as November.

Although Kymriah’s price tag has “shattered oncology drug pricing norms,” said Leonard Saltz, MD, chief of gastrointestinal oncology at Memorial Sloan Kettering Cancer Center in New York, “the sticker price is just the starting point.”

These therapies lead to a cascade of costs, propelled by serious side effects that require sophisticated management, Dr. Saltz said. For this class of drugs, Dr, Saltz advised consumers to “think of the $475,000 as parts, not labor.”

Hagop Kantarjian, MD, leukemia specialist and professor at the University of Texas MD Anderson Cancer Center, estimates tisagenlecleucel’s total cost could reach $1.5 million.

CAR T-cell therapy is expensive because of the unique way that it works. Doctors harvest patients’ immune cells, genetically alter them to rev up their ability to fight cancer, then reinfuse them into patients.

Taking the brakes off the immune system, Dr. Kantarjian said, can lead to life-threatening complications that require lengthy hospitalizations and expensive medications, which are prescribed in addition to conventional cancer therapy, rather than in place of it.

Keith D. Eaton, MD, a Seattle oncologist, said he ran up medical bills of $500,000 when he participated in a clinical trial of CAR T cells in 2013, even though all patients in the study received the medication for free. Dr. Eaton, who was diagnosed with acute lymphoblastic leukemia (ALL), spent nearly 2 months in the hospital.

Like Dr. Eaton, nearly half of patients who receive CAR T cells develop cytokine storm. Other serious side effects include strokelike symptoms and coma.

The cytokine storm felt like “the worst flu of your life,” said Dr. Eaton, now aged 51 years. His fever spiked so high that a hospital nurse assumed the thermometer was broken. Dr. Eaton replied, “It’s not broken. My temperature is too high to register on the thermometer.”

Although Dr. Eaton recovered, he wasn’t done with treatment. His doctors recommended a bone marrow transplant, another harrowing procedure, at a cost of hundreds of thousands of dollars.

Dr. Eaton said he feels fortunate to be healthy today, with tests showing no evidence of leukemia. His insurer paid for almost everything.

Kymriah’s sticker price is especially “outrageous” given its relatively low manufacturing costs, said Walid F. Gellad, MD, codirector of the Center for Pharmaceutical Policy and Prescribing at the University of Pittsburgh.

The gene therapy process used to create tisagenlecleucel costs about $15,000, according to a 2012 presentation by Carl H. June, MD, who pioneered CAR T-cell research at the University of Pennsylvania in Philadelphia. Dr. June could not be reached for comment.

To quell unrest about price, Novartis has offered patients and insurers a new twist on the money-back guarantee.

Novartis will charge for the drug only if patients go into remission within 1 month of treatment. In a key clinical trial, 83% of the children and young adults treated with tisagenlecleucel went into remission within 3 months. Novartis calls the plan “outcomes-based pricing.”

Novartis is “working through the specific details” of how the pricing plan will affect the Centers for Medicare & Medicaid Services, which pays for care for many cancer patients, company spokesperson Julie Masow said. “There are many hurdles” to this type of pricing plan but, Ms. Masow said, “Novartis is committed to making this happen.”

She also said that Kymriah’s manufacturing costs are much higher than $15,000, although she didn’t cite a specific dollar amount. She noted that Novartis has invested heavily in the technology, designing “an innovative manufacturing facility and process specifically for cellular therapies.”

As for Kymriah-related hospital and medication charges, “costs will vary from patient to patient and treatment center to treatment center, based on the level of care each patient requires,” Ms. Masow said. “Kymriah is a one-time treatment that has shown remarkable early, deep, and durable responses in these children who are very sick and often out of options.”

Some doctors said tisagenlecleucel, which could be used by about 600 patients a year, offers an incalculable benefit for desperately ill young people. The drug is approved for children and young adults with B-cell ALL who already have been treated with at least two other cancer therapies.

“A kid’s life is priceless,” said Michelle Hermiston, MD, director of pediatric immunotherapy at Benioff Children’s Hospital, at the University of California, San Francisco. “Any given kid has the potential to make financial impacts over a lifetime that far outweigh the cost of their cure. From this perspective, every child in my mind deserves the best curative therapy we can offer.”

Other cancer doctors say the Novartis plan is no bargain.

About 36% of patients who go into remission with tisagenlecleucel relapse within 1 year, said Vinay Prasad, MD, of Oregon Health & Science University, Portland. Many of these patients will need additional treatment, said Dr. Prasad, who wrote an editorial about tisagenlecleucel’s price Oct. 4 in Nature.

“If you’ve paid half a million dollars for drugs and half a million dollars for care, and a year later your cancer is back, is that a good deal?” asked Dr. Saltz, who cowrote a recent editorial on tisagenlecleucel’s price in JAMA.

Steve Miller, MD, chief medical officer for Express Scripts, said it would be more fair to judge Kymriah’s success after 6 months of treatment, rather than 1 month. Dr. Prasad goes even further. He said Novartis should issue refunds for any patient who relapses within 3 years.

A consumer-advocate group called Patients for Affordable Drugs also has said that tisagenlecleucel costs too much, given that the federal government spent more than $200 million over 2 decades to support the basic research into CAR T-cell therapy, long before Novartis bought the rights.

Rep. Lloyd Doggett (D-Texas) wrote a letter to the Medicare program’s director last month asking for details on how the Novartis payment deal will work.

“As Big Pharma continues to put price gouging before patient access, companies will point more and more proudly at their pricing agreements,” Rep. Doggett wrote. “But taxpayers deserve to know more about how these agreements will work – whether they will actually save the government money, defray these massive costs, and ensure that they can access lifesaving medications.”
 

KHN’s coverage related to aging & improving care of older adults is supported by The John A. Hartford Foundation. Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

Outrage over the high cost of cancer care has focused on skyrocketing drug prices, including the $475,000 price tag for the country’s first gene therapy, Novartis’ Kymriah (tisagenlecleucel), a leukemia treatment approved in August.

But the total costs of tisagenlecleucel and the 21 similar drugs in development – known as CAR T-cell therapies – will be far higher than many have imagined, reaching $1 million or more per patient, according to leading cancer experts. The next CAR T-cell drug could be approved as soon as November.

Although Kymriah’s price tag has “shattered oncology drug pricing norms,” said Leonard Saltz, MD, chief of gastrointestinal oncology at Memorial Sloan Kettering Cancer Center in New York, “the sticker price is just the starting point.”

These therapies lead to a cascade of costs, propelled by serious side effects that require sophisticated management, Dr. Saltz said. For this class of drugs, Dr, Saltz advised consumers to “think of the $475,000 as parts, not labor.”

Hagop Kantarjian, MD, leukemia specialist and professor at the University of Texas MD Anderson Cancer Center, estimates tisagenlecleucel’s total cost could reach $1.5 million.

CAR T-cell therapy is expensive because of the unique way that it works. Doctors harvest patients’ immune cells, genetically alter them to rev up their ability to fight cancer, then reinfuse them into patients.

Taking the brakes off the immune system, Dr. Kantarjian said, can lead to life-threatening complications that require lengthy hospitalizations and expensive medications, which are prescribed in addition to conventional cancer therapy, rather than in place of it.

Keith D. Eaton, MD, a Seattle oncologist, said he ran up medical bills of $500,000 when he participated in a clinical trial of CAR T cells in 2013, even though all patients in the study received the medication for free. Dr. Eaton, who was diagnosed with acute lymphoblastic leukemia (ALL), spent nearly 2 months in the hospital.

Like Dr. Eaton, nearly half of patients who receive CAR T cells develop cytokine storm. Other serious side effects include strokelike symptoms and coma.

The cytokine storm felt like “the worst flu of your life,” said Dr. Eaton, now aged 51 years. His fever spiked so high that a hospital nurse assumed the thermometer was broken. Dr. Eaton replied, “It’s not broken. My temperature is too high to register on the thermometer.”

Although Dr. Eaton recovered, he wasn’t done with treatment. His doctors recommended a bone marrow transplant, another harrowing procedure, at a cost of hundreds of thousands of dollars.

Dr. Eaton said he feels fortunate to be healthy today, with tests showing no evidence of leukemia. His insurer paid for almost everything.

Kymriah’s sticker price is especially “outrageous” given its relatively low manufacturing costs, said Walid F. Gellad, MD, codirector of the Center for Pharmaceutical Policy and Prescribing at the University of Pittsburgh.

The gene therapy process used to create tisagenlecleucel costs about $15,000, according to a 2012 presentation by Carl H. June, MD, who pioneered CAR T-cell research at the University of Pennsylvania in Philadelphia. Dr. June could not be reached for comment.

To quell unrest about price, Novartis has offered patients and insurers a new twist on the money-back guarantee.

Novartis will charge for the drug only if patients go into remission within 1 month of treatment. In a key clinical trial, 83% of the children and young adults treated with tisagenlecleucel went into remission within 3 months. Novartis calls the plan “outcomes-based pricing.”

Novartis is “working through the specific details” of how the pricing plan will affect the Centers for Medicare & Medicaid Services, which pays for care for many cancer patients, company spokesperson Julie Masow said. “There are many hurdles” to this type of pricing plan but, Ms. Masow said, “Novartis is committed to making this happen.”

She also said that Kymriah’s manufacturing costs are much higher than $15,000, although she didn’t cite a specific dollar amount. She noted that Novartis has invested heavily in the technology, designing “an innovative manufacturing facility and process specifically for cellular therapies.”

As for Kymriah-related hospital and medication charges, “costs will vary from patient to patient and treatment center to treatment center, based on the level of care each patient requires,” Ms. Masow said. “Kymriah is a one-time treatment that has shown remarkable early, deep, and durable responses in these children who are very sick and often out of options.”

Some doctors said tisagenlecleucel, which could be used by about 600 patients a year, offers an incalculable benefit for desperately ill young people. The drug is approved for children and young adults with B-cell ALL who already have been treated with at least two other cancer therapies.

“A kid’s life is priceless,” said Michelle Hermiston, MD, director of pediatric immunotherapy at Benioff Children’s Hospital, at the University of California, San Francisco. “Any given kid has the potential to make financial impacts over a lifetime that far outweigh the cost of their cure. From this perspective, every child in my mind deserves the best curative therapy we can offer.”

Other cancer doctors say the Novartis plan is no bargain.

About 36% of patients who go into remission with tisagenlecleucel relapse within 1 year, said Vinay Prasad, MD, of Oregon Health & Science University, Portland. Many of these patients will need additional treatment, said Dr. Prasad, who wrote an editorial about tisagenlecleucel’s price Oct. 4 in Nature.

“If you’ve paid half a million dollars for drugs and half a million dollars for care, and a year later your cancer is back, is that a good deal?” asked Dr. Saltz, who cowrote a recent editorial on tisagenlecleucel’s price in JAMA.

Steve Miller, MD, chief medical officer for Express Scripts, said it would be more fair to judge Kymriah’s success after 6 months of treatment, rather than 1 month. Dr. Prasad goes even further. He said Novartis should issue refunds for any patient who relapses within 3 years.

A consumer-advocate group called Patients for Affordable Drugs also has said that tisagenlecleucel costs too much, given that the federal government spent more than $200 million over 2 decades to support the basic research into CAR T-cell therapy, long before Novartis bought the rights.

Rep. Lloyd Doggett (D-Texas) wrote a letter to the Medicare program’s director last month asking for details on how the Novartis payment deal will work.

“As Big Pharma continues to put price gouging before patient access, companies will point more and more proudly at their pricing agreements,” Rep. Doggett wrote. “But taxpayers deserve to know more about how these agreements will work – whether they will actually save the government money, defray these massive costs, and ensure that they can access lifesaving medications.”
 

KHN’s coverage related to aging & improving care of older adults is supported by The John A. Hartford Foundation. Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

Outrage over the high cost of cancer care has focused on skyrocketing drug prices, including the $475,000 price tag for the country’s first gene therapy, Novartis’ Kymriah (tisagenlecleucel), a leukemia treatment approved in August.

But the total costs of tisagenlecleucel and the 21 similar drugs in development – known as CAR T-cell therapies – will be far higher than many have imagined, reaching $1 million or more per patient, according to leading cancer experts. The next CAR T-cell drug could be approved as soon as November.

Although Kymriah’s price tag has “shattered oncology drug pricing norms,” said Leonard Saltz, MD, chief of gastrointestinal oncology at Memorial Sloan Kettering Cancer Center in New York, “the sticker price is just the starting point.”

These therapies lead to a cascade of costs, propelled by serious side effects that require sophisticated management, Dr. Saltz said. For this class of drugs, Dr, Saltz advised consumers to “think of the $475,000 as parts, not labor.”

Hagop Kantarjian, MD, leukemia specialist and professor at the University of Texas MD Anderson Cancer Center, estimates tisagenlecleucel’s total cost could reach $1.5 million.

CAR T-cell therapy is expensive because of the unique way that it works. Doctors harvest patients’ immune cells, genetically alter them to rev up their ability to fight cancer, then reinfuse them into patients.

Taking the brakes off the immune system, Dr. Kantarjian said, can lead to life-threatening complications that require lengthy hospitalizations and expensive medications, which are prescribed in addition to conventional cancer therapy, rather than in place of it.

Keith D. Eaton, MD, a Seattle oncologist, said he ran up medical bills of $500,000 when he participated in a clinical trial of CAR T cells in 2013, even though all patients in the study received the medication for free. Dr. Eaton, who was diagnosed with acute lymphoblastic leukemia (ALL), spent nearly 2 months in the hospital.

Like Dr. Eaton, nearly half of patients who receive CAR T cells develop cytokine storm. Other serious side effects include strokelike symptoms and coma.

The cytokine storm felt like “the worst flu of your life,” said Dr. Eaton, now aged 51 years. His fever spiked so high that a hospital nurse assumed the thermometer was broken. Dr. Eaton replied, “It’s not broken. My temperature is too high to register on the thermometer.”

Although Dr. Eaton recovered, he wasn’t done with treatment. His doctors recommended a bone marrow transplant, another harrowing procedure, at a cost of hundreds of thousands of dollars.

Dr. Eaton said he feels fortunate to be healthy today, with tests showing no evidence of leukemia. His insurer paid for almost everything.

Kymriah’s sticker price is especially “outrageous” given its relatively low manufacturing costs, said Walid F. Gellad, MD, codirector of the Center for Pharmaceutical Policy and Prescribing at the University of Pittsburgh.

The gene therapy process used to create tisagenlecleucel costs about $15,000, according to a 2012 presentation by Carl H. June, MD, who pioneered CAR T-cell research at the University of Pennsylvania in Philadelphia. Dr. June could not be reached for comment.

To quell unrest about price, Novartis has offered patients and insurers a new twist on the money-back guarantee.

Novartis will charge for the drug only if patients go into remission within 1 month of treatment. In a key clinical trial, 83% of the children and young adults treated with tisagenlecleucel went into remission within 3 months. Novartis calls the plan “outcomes-based pricing.”

Novartis is “working through the specific details” of how the pricing plan will affect the Centers for Medicare & Medicaid Services, which pays for care for many cancer patients, company spokesperson Julie Masow said. “There are many hurdles” to this type of pricing plan but, Ms. Masow said, “Novartis is committed to making this happen.”

She also said that Kymriah’s manufacturing costs are much higher than $15,000, although she didn’t cite a specific dollar amount. She noted that Novartis has invested heavily in the technology, designing “an innovative manufacturing facility and process specifically for cellular therapies.”

As for Kymriah-related hospital and medication charges, “costs will vary from patient to patient and treatment center to treatment center, based on the level of care each patient requires,” Ms. Masow said. “Kymriah is a one-time treatment that has shown remarkable early, deep, and durable responses in these children who are very sick and often out of options.”

Some doctors said tisagenlecleucel, which could be used by about 600 patients a year, offers an incalculable benefit for desperately ill young people. The drug is approved for children and young adults with B-cell ALL who already have been treated with at least two other cancer therapies.

“A kid’s life is priceless,” said Michelle Hermiston, MD, director of pediatric immunotherapy at Benioff Children’s Hospital, at the University of California, San Francisco. “Any given kid has the potential to make financial impacts over a lifetime that far outweigh the cost of their cure. From this perspective, every child in my mind deserves the best curative therapy we can offer.”

Other cancer doctors say the Novartis plan is no bargain.

About 36% of patients who go into remission with tisagenlecleucel relapse within 1 year, said Vinay Prasad, MD, of Oregon Health & Science University, Portland. Many of these patients will need additional treatment, said Dr. Prasad, who wrote an editorial about tisagenlecleucel’s price Oct. 4 in Nature.

“If you’ve paid half a million dollars for drugs and half a million dollars for care, and a year later your cancer is back, is that a good deal?” asked Dr. Saltz, who cowrote a recent editorial on tisagenlecleucel’s price in JAMA.

Steve Miller, MD, chief medical officer for Express Scripts, said it would be more fair to judge Kymriah’s success after 6 months of treatment, rather than 1 month. Dr. Prasad goes even further. He said Novartis should issue refunds for any patient who relapses within 3 years.

A consumer-advocate group called Patients for Affordable Drugs also has said that tisagenlecleucel costs too much, given that the federal government spent more than $200 million over 2 decades to support the basic research into CAR T-cell therapy, long before Novartis bought the rights.

Rep. Lloyd Doggett (D-Texas) wrote a letter to the Medicare program’s director last month asking for details on how the Novartis payment deal will work.

“As Big Pharma continues to put price gouging before patient access, companies will point more and more proudly at their pricing agreements,” Rep. Doggett wrote. “But taxpayers deserve to know more about how these agreements will work – whether they will actually save the government money, defray these massive costs, and ensure that they can access lifesaving medications.”
 

KHN’s coverage related to aging & improving care of older adults is supported by The John A. Hartford Foundation. Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

The overall response rate to immune checkpoint inhibitors was 45% among cancer patients who had more than three variants of unknown significance in their circulating tumor DNA; among those with three or fewer, the response rate was 15%, according to a University of California, San Diego, investigation with 69 subjects.

Higher mutation burdens in circulating tumor DNA (ctDNA) also correlated with improved progression-free and overall survival across 20 cancer types, the investigators reported (Clin Cancer Res. 2017 Oct. 1. doi: 10.1158/1078-0432.CCR-17-1439).

Tumor mutation burdens can predict response to checkpoint inhibitors, but they are usually assessed by tissue biopsy, which is costly and invasive. The findings suggest that blood tests could replace tissue biopsies to green-light immune checkpoint inhibitor treatment.

“Our current results may be clinically exploitable. ... Liquid biopsies that assess blood-derived ctDNA are noninvasive, easily acquired, and inexpensive. The ctDNA derived from blood may also represent shed DNA from multiple metastatic sites, whereas tissue genomics reflects only the piece of tissue removed,” said investigators led by Yulian Khagi, MD, a hematology-oncology fellow at the university.

In a press statement, Dr. Khagi said “If verified by further studies, clinicians will be able to utilize the ... results of this simple blood test to make determinations about whether to use checkpoint inhibitor–based immune therapy in a variety of tumor types.”

The 69 patients were a median of 56 years old, and 43 (62.3%) were men. Melanoma, lung cancer, and head and neck cancer were the most common malignancies. The majority of patients had anti–PD-1 or PD-L1 monotherapy.

For most patients, blood samples were drawn a month or 2 before treatment. Next-generation sequencing (Guardant360) was done on ctDNA to detect alterations in cancer genes. Of the 69 patients, 20 (29%) had more than three variants of unknown significance (VUS); the rest had three or fewer.

The median overall survival was 15.3 months from the start of immunotherapy. For patients with three or fewer VUS, median overall survival was 10.72 months; for patients with more, median overall survival could not be calculated because more than half were alive at the study’s conclusion.

Median progression-fee survival was 2.07 months with three or fewer VUS, versus 3.84 months with more. The findings were statistically significant.

Similar results were found when all genomic alterations, not just VUS, were examined and dichotomized as six or more versus fewer than six.

“The number of genes assayed in our ctDNA analysis was only between 54 and 70. Unlike targeted NGS [next-generation sequencing] of tumor tissue, which often tests for hundreds of genes and allows a relatively accurate estimate of total mutational burden, targeted NGS of plasma ctDNA provides only a limited snapshot of the cancer genome. More extensive ctDNA gene panels merit investigation to determine if they increase the correlative value of our findings,” the investigators said.

The work was funded by the Joan and Irwin Jacobs Fund and the National Cancer Institute. Dr. Khagi had no industry disclosures. Three authors reported financial ties to a number of companies, including Boehringer, Merck, Guardant, and Pfizer. The senior author has ownership interests in CureMatch.

[email protected]

The overall response rate to immune checkpoint inhibitors was 45% among cancer patients who had more than three variants of unknown significance in their circulating tumor DNA; among those with three or fewer, the response rate was 15%, according to a University of California, San Diego, investigation with 69 subjects.

Higher mutation burdens in circulating tumor DNA (ctDNA) also correlated with improved progression-free and overall survival across 20 cancer types, the investigators reported (Clin Cancer Res. 2017 Oct. 1. doi: 10.1158/1078-0432.CCR-17-1439).

Tumor mutation burdens can predict response to checkpoint inhibitors, but they are usually assessed by tissue biopsy, which is costly and invasive. The findings suggest that blood tests could replace tissue biopsies to green-light immune checkpoint inhibitor treatment.

“Our current results may be clinically exploitable. ... Liquid biopsies that assess blood-derived ctDNA are noninvasive, easily acquired, and inexpensive. The ctDNA derived from blood may also represent shed DNA from multiple metastatic sites, whereas tissue genomics reflects only the piece of tissue removed,” said investigators led by Yulian Khagi, MD, a hematology-oncology fellow at the university.

In a press statement, Dr. Khagi said “If verified by further studies, clinicians will be able to utilize the ... results of this simple blood test to make determinations about whether to use checkpoint inhibitor–based immune therapy in a variety of tumor types.”

The 69 patients were a median of 56 years old, and 43 (62.3%) were men. Melanoma, lung cancer, and head and neck cancer were the most common malignancies. The majority of patients had anti–PD-1 or PD-L1 monotherapy.

For most patients, blood samples were drawn a month or 2 before treatment. Next-generation sequencing (Guardant360) was done on ctDNA to detect alterations in cancer genes. Of the 69 patients, 20 (29%) had more than three variants of unknown significance (VUS); the rest had three or fewer.

The median overall survival was 15.3 months from the start of immunotherapy. For patients with three or fewer VUS, median overall survival was 10.72 months; for patients with more, median overall survival could not be calculated because more than half were alive at the study’s conclusion.

Median progression-fee survival was 2.07 months with three or fewer VUS, versus 3.84 months with more. The findings were statistically significant.

Similar results were found when all genomic alterations, not just VUS, were examined and dichotomized as six or more versus fewer than six.

“The number of genes assayed in our ctDNA analysis was only between 54 and 70. Unlike targeted NGS [next-generation sequencing] of tumor tissue, which often tests for hundreds of genes and allows a relatively accurate estimate of total mutational burden, targeted NGS of plasma ctDNA provides only a limited snapshot of the cancer genome. More extensive ctDNA gene panels merit investigation to determine if they increase the correlative value of our findings,” the investigators said.

The work was funded by the Joan and Irwin Jacobs Fund and the National Cancer Institute. Dr. Khagi had no industry disclosures. Three authors reported financial ties to a number of companies, including Boehringer, Merck, Guardant, and Pfizer. The senior author has ownership interests in CureMatch.

[email protected]

The overall response rate to immune checkpoint inhibitors was 45% among cancer patients who had more than three variants of unknown significance in their circulating tumor DNA; among those with three or fewer, the response rate was 15%, according to a University of California, San Diego, investigation with 69 subjects.

Higher mutation burdens in circulating tumor DNA (ctDNA) also correlated with improved progression-free and overall survival across 20 cancer types, the investigators reported (Clin Cancer Res. 2017 Oct. 1. doi: 10.1158/1078-0432.CCR-17-1439).

Tumor mutation burdens can predict response to checkpoint inhibitors, but they are usually assessed by tissue biopsy, which is costly and invasive. The findings suggest that blood tests could replace tissue biopsies to green-light immune checkpoint inhibitor treatment.

“Our current results may be clinically exploitable. ... Liquid biopsies that assess blood-derived ctDNA are noninvasive, easily acquired, and inexpensive. The ctDNA derived from blood may also represent shed DNA from multiple metastatic sites, whereas tissue genomics reflects only the piece of tissue removed,” said investigators led by Yulian Khagi, MD, a hematology-oncology fellow at the university.

In a press statement, Dr. Khagi said “If verified by further studies, clinicians will be able to utilize the ... results of this simple blood test to make determinations about whether to use checkpoint inhibitor–based immune therapy in a variety of tumor types.”

The 69 patients were a median of 56 years old, and 43 (62.3%) were men. Melanoma, lung cancer, and head and neck cancer were the most common malignancies. The majority of patients had anti–PD-1 or PD-L1 monotherapy.

For most patients, blood samples were drawn a month or 2 before treatment. Next-generation sequencing (Guardant360) was done on ctDNA to detect alterations in cancer genes. Of the 69 patients, 20 (29%) had more than three variants of unknown significance (VUS); the rest had three or fewer.

The median overall survival was 15.3 months from the start of immunotherapy. For patients with three or fewer VUS, median overall survival was 10.72 months; for patients with more, median overall survival could not be calculated because more than half were alive at the study’s conclusion.

Median progression-fee survival was 2.07 months with three or fewer VUS, versus 3.84 months with more. The findings were statistically significant.

Similar results were found when all genomic alterations, not just VUS, were examined and dichotomized as six or more versus fewer than six.

“The number of genes assayed in our ctDNA analysis was only between 54 and 70. Unlike targeted NGS [next-generation sequencing] of tumor tissue, which often tests for hundreds of genes and allows a relatively accurate estimate of total mutational burden, targeted NGS of plasma ctDNA provides only a limited snapshot of the cancer genome. More extensive ctDNA gene panels merit investigation to determine if they increase the correlative value of our findings,” the investigators said.

The work was funded by the Joan and Irwin Jacobs Fund and the National Cancer Institute. Dr. Khagi had no industry disclosures. Three authors reported financial ties to a number of companies, including Boehringer, Merck, Guardant, and Pfizer. The senior author has ownership interests in CureMatch.

[email protected]

MADRID – A combination of two immune checkpoint inhibitors was superior to the tyrosine kinase inhibitor (TKI) sunitinib (Sutent) in first-line treatment of patients with advanced or metastatic renal cell carcinoma (RCC), investigators reported

Median overall survival (OS) among 425 patients with intermediate- or poor-risk treatment-naive advanced/metastatic clear-cell RCC treated with the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) was not reached after 32 months of follow-up. In contrast, the median OS for 422 patients treated with sunitinib was 26 months, reported Bernard Escudier, MD from the Institut Gustave Roussy in Villejuif, France.

[email protected]

MADRID – A combination of two immune checkpoint inhibitors was superior to the tyrosine kinase inhibitor (TKI) sunitinib (Sutent) in first-line treatment of patients with advanced or metastatic renal cell carcinoma (RCC), investigators reported

Median overall survival (OS) among 425 patients with intermediate- or poor-risk treatment-naive advanced/metastatic clear-cell RCC treated with the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) was not reached after 32 months of follow-up. In contrast, the median OS for 422 patients treated with sunitinib was 26 months, reported Bernard Escudier, MD from the Institut Gustave Roussy in Villejuif, France.

[email protected]

MADRID – A combination of two immune checkpoint inhibitors was superior to the tyrosine kinase inhibitor (TKI) sunitinib (Sutent) in first-line treatment of patients with advanced or metastatic renal cell carcinoma (RCC), investigators reported

Median overall survival (OS) among 425 patients with intermediate- or poor-risk treatment-naive advanced/metastatic clear-cell RCC treated with the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) was not reached after 32 months of follow-up. In contrast, the median OS for 422 patients treated with sunitinib was 26 months, reported Bernard Escudier, MD from the Institut Gustave Roussy in Villejuif, France.

[email protected]

The Food and Drug Administration has approved pembrolizumab (Keytruda) for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma, in cases where tests confirm that the tumors contain programmed death–ligand 1 and where the disease is progressing on or after two or more prior lines of therapy.

Pembrolizumab has been approved in the United States since 2014 for the treatment of melanoma, with subsequent approvals for treatment of non–small-cell lung cancer, head and neck squamous cell carcinoma, Hodgkin lymphoma, and several other advanced cancers.

[email protected]

The Food and Drug Administration has approved pembrolizumab (Keytruda) for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma, in cases where tests confirm that the tumors contain programmed death–ligand 1 and where the disease is progressing on or after two or more prior lines of therapy.

Pembrolizumab has been approved in the United States since 2014 for the treatment of melanoma, with subsequent approvals for treatment of non–small-cell lung cancer, head and neck squamous cell carcinoma, Hodgkin lymphoma, and several other advanced cancers.

[email protected]

The Food and Drug Administration has approved pembrolizumab (Keytruda) for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma, in cases where tests confirm that the tumors contain programmed death–ligand 1 and where the disease is progressing on or after two or more prior lines of therapy.

Pembrolizumab has been approved in the United States since 2014 for the treatment of melanoma, with subsequent approvals for treatment of non–small-cell lung cancer, head and neck squamous cell carcinoma, Hodgkin lymphoma, and several other advanced cancers.

[email protected]

CHICAGO – Exposure to radiation therapy prior to PD-1/PD-L1 therapy was not associated with improved outcomes in a retrospective review of 66 lung cancer patients.

The patients had stage IIIB or IV non–small cell lung cancer, median age of 64 years, received at least 6 weeks of single-agent anti-PD-1/PD-L1 therapy in the second-line setting or beyond, and had survived at least 8 weeks from immunotherapy initiation. Compared with 13 patients who received no radiation therapy, the 53 who received any prior radiation therapy – including 44 with extracranial radiation and 22 with intracranial radiation – did not differ significantly with respect to progression-free survival (median 4-5 months; hazard ratio, 0.83), or overall survival (median of about 12 months in both groups; HR, 0.96), Christopher Strouse, MD, of the University of Iowa, Iowa City, reported at the Chicago Multidisciplinary Symposium in Thoracic Oncology.

There also were no significant differences in the outcomes between those who had extracranial radiation and those who had intracranial radiation (HRs for PFS and OS, respectively, 0.91 and 1.19), or (on univariate analysis), between those receiving any vs. no intracranial radiation therapy (HRs for PFS and OS, respectively, 0.92 and 0.98), Dr. Strouse said.

The patients who received extracranial radiation therapy had lower lymphocyte counts at the time of anti-PD-1/PD-L1 therapy initiation vs. those who received only radiation therapy (mean lymphocyte count, 809 vs. 1,519), and those who received intracranial radiation therapy were younger than those who did not (median age, 59 vs. 65 years), but the groups were similar with respect to other variables, including gender, histology, performance status, smoking history, KRAS mutation, and number of prior lines of systemic therapies. Anti-PD-1/PD-L1 therapies are promising treatment options for metastatic non–small cell lung cancer, and combining these agents with other immune-modulating therapies may enhance their efficacy and lead to a greater proportion of patients with responses to these treatments, Dr. Strouse noted.

“It’s known that immune response depends on a lot of steps, even beyond the PD-1/PD-L1 axis, and one possible explanation for some of these patients [not responding] may be that there is some failure along the way in some other step,” he said. “Our hypothesis was that radiation therapy would be helpful in overcoming some of these barriers.”

However, in this study, which is limited by small sample size and single-institution retrospective design, no such effect was identified.

The findings conflict with some larger studies, including the recently-reported PACIFIC study, which showed a significant PFS benefit in lung cancer patients who received chemoradiation therapy followed by treatment with the PD-L1 inhibitor durvalumab.

Dr. Strouse said he looks forward to seeing further reports looking into the effects of radiation therapy at different doses and timing.

Invited discussant Heather Wakelee, MD, of Stanford (Calif.) University, also stressed the limitations of the University of Iowa study, and noted that while there are many unanswered questions, findings such as those from the PACIFIC trial show that radiation and PD-L1 inhibition is here to stay.

“It appears safe; there will be more coming,” she said.

Dr. Strouse reported having no disclosures. Dr. Wakelee has been the institutional principal investigator for studies of nivolumab, tocilizumab, and other agents. She has consulted for Peregrine, ACEA, Pfizer, Helsinn, Genentech/Roche, Clovis, and Lilly, and received research/grant support from Clovis, Exelixis, AstraZeneca/Medimmune, Genentech/Roche, BMS, Gilead, Novartis, Xcovery, Pfizer, Celgene, Gilead, Pharmacyclics, and Lilly.

[email protected]

CHICAGO – Exposure to radiation therapy prior to PD-1/PD-L1 therapy was not associated with improved outcomes in a retrospective review of 66 lung cancer patients.

The patients had stage IIIB or IV non–small cell lung cancer, median age of 64 years, received at least 6 weeks of single-agent anti-PD-1/PD-L1 therapy in the second-line setting or beyond, and had survived at least 8 weeks from immunotherapy initiation. Compared with 13 patients who received no radiation therapy, the 53 who received any prior radiation therapy – including 44 with extracranial radiation and 22 with intracranial radiation – did not differ significantly with respect to progression-free survival (median 4-5 months; hazard ratio, 0.83), or overall survival (median of about 12 months in both groups; HR, 0.96), Christopher Strouse, MD, of the University of Iowa, Iowa City, reported at the Chicago Multidisciplinary Symposium in Thoracic Oncology.

There also were no significant differences in the outcomes between those who had extracranial radiation and those who had intracranial radiation (HRs for PFS and OS, respectively, 0.91 and 1.19), or (on univariate analysis), between those receiving any vs. no intracranial radiation therapy (HRs for PFS and OS, respectively, 0.92 and 0.98), Dr. Strouse said.

The patients who received extracranial radiation therapy had lower lymphocyte counts at the time of anti-PD-1/PD-L1 therapy initiation vs. those who received only radiation therapy (mean lymphocyte count, 809 vs. 1,519), and those who received intracranial radiation therapy were younger than those who did not (median age, 59 vs. 65 years), but the groups were similar with respect to other variables, including gender, histology, performance status, smoking history, KRAS mutation, and number of prior lines of systemic therapies. Anti-PD-1/PD-L1 therapies are promising treatment options for metastatic non–small cell lung cancer, and combining these agents with other immune-modulating therapies may enhance their efficacy and lead to a greater proportion of patients with responses to these treatments, Dr. Strouse noted.

“It’s known that immune response depends on a lot of steps, even beyond the PD-1/PD-L1 axis, and one possible explanation for some of these patients [not responding] may be that there is some failure along the way in some other step,” he said. “Our hypothesis was that radiation therapy would be helpful in overcoming some of these barriers.”

However, in this study, which is limited by small sample size and single-institution retrospective design, no such effect was identified.

The findings conflict with some larger studies, including the recently-reported PACIFIC study, which showed a significant PFS benefit in lung cancer patients who received chemoradiation therapy followed by treatment with the PD-L1 inhibitor durvalumab.

Dr. Strouse said he looks forward to seeing further reports looking into the effects of radiation therapy at different doses and timing.

Invited discussant Heather Wakelee, MD, of Stanford (Calif.) University, also stressed the limitations of the University of Iowa study, and noted that while there are many unanswered questions, findings such as those from the PACIFIC trial show that radiation and PD-L1 inhibition is here to stay.

“It appears safe; there will be more coming,” she said.

Dr. Strouse reported having no disclosures. Dr. Wakelee has been the institutional principal investigator for studies of nivolumab, tocilizumab, and other agents. She has consulted for Peregrine, ACEA, Pfizer, Helsinn, Genentech/Roche, Clovis, and Lilly, and received research/grant support from Clovis, Exelixis, AstraZeneca/Medimmune, Genentech/Roche, BMS, Gilead, Novartis, Xcovery, Pfizer, Celgene, Gilead, Pharmacyclics, and Lilly.

[email protected]

CHICAGO – Exposure to radiation therapy prior to PD-1/PD-L1 therapy was not associated with improved outcomes in a retrospective review of 66 lung cancer patients.

The patients had stage IIIB or IV non–small cell lung cancer, median age of 64 years, received at least 6 weeks of single-agent anti-PD-1/PD-L1 therapy in the second-line setting or beyond, and had survived at least 8 weeks from immunotherapy initiation. Compared with 13 patients who received no radiation therapy, the 53 who received any prior radiation therapy – including 44 with extracranial radiation and 22 with intracranial radiation – did not differ significantly with respect to progression-free survival (median 4-5 months; hazard ratio, 0.83), or overall survival (median of about 12 months in both groups; HR, 0.96), Christopher Strouse, MD, of the University of Iowa, Iowa City, reported at the Chicago Multidisciplinary Symposium in Thoracic Oncology.

There also were no significant differences in the outcomes between those who had extracranial radiation and those who had intracranial radiation (HRs for PFS and OS, respectively, 0.91 and 1.19), or (on univariate analysis), between those receiving any vs. no intracranial radiation therapy (HRs for PFS and OS, respectively, 0.92 and 0.98), Dr. Strouse said.

The patients who received extracranial radiation therapy had lower lymphocyte counts at the time of anti-PD-1/PD-L1 therapy initiation vs. those who received only radiation therapy (mean lymphocyte count, 809 vs. 1,519), and those who received intracranial radiation therapy were younger than those who did not (median age, 59 vs. 65 years), but the groups were similar with respect to other variables, including gender, histology, performance status, smoking history, KRAS mutation, and number of prior lines of systemic therapies. Anti-PD-1/PD-L1 therapies are promising treatment options for metastatic non–small cell lung cancer, and combining these agents with other immune-modulating therapies may enhance their efficacy and lead to a greater proportion of patients with responses to these treatments, Dr. Strouse noted.

“It’s known that immune response depends on a lot of steps, even beyond the PD-1/PD-L1 axis, and one possible explanation for some of these patients [not responding] may be that there is some failure along the way in some other step,” he said. “Our hypothesis was that radiation therapy would be helpful in overcoming some of these barriers.”

However, in this study, which is limited by small sample size and single-institution retrospective design, no such effect was identified.

The findings conflict with some larger studies, including the recently-reported PACIFIC study, which showed a significant PFS benefit in lung cancer patients who received chemoradiation therapy followed by treatment with the PD-L1 inhibitor durvalumab.

Dr. Strouse said he looks forward to seeing further reports looking into the effects of radiation therapy at different doses and timing.

Invited discussant Heather Wakelee, MD, of Stanford (Calif.) University, also stressed the limitations of the University of Iowa study, and noted that while there are many unanswered questions, findings such as those from the PACIFIC trial show that radiation and PD-L1 inhibition is here to stay.

“It appears safe; there will be more coming,” she said.

Dr. Strouse reported having no disclosures. Dr. Wakelee has been the institutional principal investigator for studies of nivolumab, tocilizumab, and other agents. She has consulted for Peregrine, ACEA, Pfizer, Helsinn, Genentech/Roche, Clovis, and Lilly, and received research/grant support from Clovis, Exelixis, AstraZeneca/Medimmune, Genentech/Roche, BMS, Gilead, Novartis, Xcovery, Pfizer, Celgene, Gilead, Pharmacyclics, and Lilly.

[email protected]

The Food and Drug Administration has granted accelerated approval to nivolumab (Optivo) for the treatment of patients with hepatocellular carcinoma (HCC) who have been treated previously with sorafenib.

Approval was based on tumor response rate and durability of response from the phase 1/2 Checkmate 040 trial. Of 154 patients with HCC in the trial who received nivolumab following progression on sorafenib, 3 experienced complete response, and 19 experienced partial response. Median time to response was 2.8 months, and 91% of patients who responded to treatment had a response length longer than 6 months, with 55% of patients having a response length longer than 1 year.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

[email protected]

The Food and Drug Administration has granted accelerated approval to nivolumab (Optivo) for the treatment of patients with hepatocellular carcinoma (HCC) who have been treated previously with sorafenib.

Approval was based on tumor response rate and durability of response from the phase 1/2 Checkmate 040 trial. Of 154 patients with HCC in the trial who received nivolumab following progression on sorafenib, 3 experienced complete response, and 19 experienced partial response. Median time to response was 2.8 months, and 91% of patients who responded to treatment had a response length longer than 6 months, with 55% of patients having a response length longer than 1 year.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

[email protected]

The Food and Drug Administration has granted accelerated approval to nivolumab (Optivo) for the treatment of patients with hepatocellular carcinoma (HCC) who have been treated previously with sorafenib.

Approval was based on tumor response rate and durability of response from the phase 1/2 Checkmate 040 trial. Of 154 patients with HCC in the trial who received nivolumab following progression on sorafenib, 3 experienced complete response, and 19 experienced partial response. Median time to response was 2.8 months, and 91% of patients who responded to treatment had a response length longer than 6 months, with 55% of patients having a response length longer than 1 year.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

[email protected]

CHICAGO – A baseline C-reactive protein (CRP) level above 50 mg/L independently predicted worse overall survival after immunotherapy in patients with advanced non–small cell lung cancer and small cell lung cancer in a retrospective study.

In 99 patients treated with nivolumab after a first-line platinum doublet, the median baseline CRP level was 22 mg/L. After a median follow-up of 8.5 months, 50% of patients were alive, and, based on univariate and multivariate analysis, both liver involvement and having a CRP level greater than 50 mg/L were significantly associated with inferior overall survival after immunotherapy.

The median overall survival after immunotherapy was 9.3 months versus 2.7 months with a CRP level of 50 mg/L or less versus above 50 mg/L, Abdul Rafeh Naqash, MD, of East Carolina University, Greenville, N.C., reported at the Chicago Multidisciplinary Symposium in Thoracic Oncology.

Notably, significant increases in CRP level, compared with baseline, were seen at the time of grade 2 to grade 4 immune-related adverse events, which occurred in 38.4% of patients. This is a hypothesis-generating finding in that it suggests there is dysregulation of the immune system, in the context of immune checkpoint blockade, that leads to a more proinflammatory state, which ultimately leads to immune-related adverse events, Dr. Naqash said.

Study subjects were adults with a median age of 65 years who were treated during April 2015-March 2017. Most were white (64.7%), were male (64.6%), and had non–small cell lung cancer (88%). Most had stage IV disease (70.7%), and the most common site for metastases was the bones (35.4%) and the liver (24.2%). Patients’ CRP levels were measured at anti-PD-1–treatment initiation and serially with subsequent doses.

The findings are important because the identification of predictive biomarkers in patients treated with anti-PD-1 therapy could provide valuable insights into underlying mechanisms regulating patient responses, elucidate resistance mechanisms, and help with optimal selection of patients for treatment with and development of patient-tailored treatment, Dr. Naqash said, noting that identifying such biomarkers has thus far been a challenge.

However, this study is limited by its retrospective design and limited follow-up; the findings require validation in prospective lung cancer trials, he concluded.

Dr. Naqash reported having no disclosures.

[email protected]
 

CHICAGO – A baseline C-reactive protein (CRP) level above 50 mg/L independently predicted worse overall survival after immunotherapy in patients with advanced non–small cell lung cancer and small cell lung cancer in a retrospective study.

In 99 patients treated with nivolumab after a first-line platinum doublet, the median baseline CRP level was 22 mg/L. After a median follow-up of 8.5 months, 50% of patients were alive, and, based on univariate and multivariate analysis, both liver involvement and having a CRP level greater than 50 mg/L were significantly associated with inferior overall survival after immunotherapy.

The median overall survival after immunotherapy was 9.3 months versus 2.7 months with a CRP level of 50 mg/L or less versus above 50 mg/L, Abdul Rafeh Naqash, MD, of East Carolina University, Greenville, N.C., reported at the Chicago Multidisciplinary Symposium in Thoracic Oncology.

Notably, significant increases in CRP level, compared with baseline, were seen at the time of grade 2 to grade 4 immune-related adverse events, which occurred in 38.4% of patients. This is a hypothesis-generating finding in that it suggests there is dysregulation of the immune system, in the context of immune checkpoint blockade, that leads to a more proinflammatory state, which ultimately leads to immune-related adverse events, Dr. Naqash said.

Study subjects were adults with a median age of 65 years who were treated during April 2015-March 2017. Most were white (64.7%), were male (64.6%), and had non–small cell lung cancer (88%). Most had stage IV disease (70.7%), and the most common site for metastases was the bones (35.4%) and the liver (24.2%). Patients’ CRP levels were measured at anti-PD-1–treatment initiation and serially with subsequent doses.

The findings are important because the identification of predictive biomarkers in patients treated with anti-PD-1 therapy could provide valuable insights into underlying mechanisms regulating patient responses, elucidate resistance mechanisms, and help with optimal selection of patients for treatment with and development of patient-tailored treatment, Dr. Naqash said, noting that identifying such biomarkers has thus far been a challenge.

However, this study is limited by its retrospective design and limited follow-up; the findings require validation in prospective lung cancer trials, he concluded.

Dr. Naqash reported having no disclosures.

[email protected]
 

CHICAGO – A baseline C-reactive protein (CRP) level above 50 mg/L independently predicted worse overall survival after immunotherapy in patients with advanced non–small cell lung cancer and small cell lung cancer in a retrospective study.

In 99 patients treated with nivolumab after a first-line platinum doublet, the median baseline CRP level was 22 mg/L. After a median follow-up of 8.5 months, 50% of patients were alive, and, based on univariate and multivariate analysis, both liver involvement and having a CRP level greater than 50 mg/L were significantly associated with inferior overall survival after immunotherapy.

The median overall survival after immunotherapy was 9.3 months versus 2.7 months with a CRP level of 50 mg/L or less versus above 50 mg/L, Abdul Rafeh Naqash, MD, of East Carolina University, Greenville, N.C., reported at the Chicago Multidisciplinary Symposium in Thoracic Oncology.

Notably, significant increases in CRP level, compared with baseline, were seen at the time of grade 2 to grade 4 immune-related adverse events, which occurred in 38.4% of patients. This is a hypothesis-generating finding in that it suggests there is dysregulation of the immune system, in the context of immune checkpoint blockade, that leads to a more proinflammatory state, which ultimately leads to immune-related adverse events, Dr. Naqash said.

Study subjects were adults with a median age of 65 years who were treated during April 2015-March 2017. Most were white (64.7%), were male (64.6%), and had non–small cell lung cancer (88%). Most had stage IV disease (70.7%), and the most common site for metastases was the bones (35.4%) and the liver (24.2%). Patients’ CRP levels were measured at anti-PD-1–treatment initiation and serially with subsequent doses.

The findings are important because the identification of predictive biomarkers in patients treated with anti-PD-1 therapy could provide valuable insights into underlying mechanisms regulating patient responses, elucidate resistance mechanisms, and help with optimal selection of patients for treatment with and development of patient-tailored treatment, Dr. Naqash said, noting that identifying such biomarkers has thus far been a challenge.

However, this study is limited by its retrospective design and limited follow-up; the findings require validation in prospective lung cancer trials, he concluded.

Dr. Naqash reported having no disclosures.

[email protected]
 

CHICAGO – Tocilizumab may be a therapeutic option for steroid-refractory immune-related adverse events that are secondary to PD-1 blockade, according to findings from a review of patients treated with nivolumab for various malignancies.

Of 87 patients who were treated with the PD-1 inhibitor between April 2015 and October 2016, 34 received tocilizumab for high-grade immune-related adverse events (irAEs) that were refractory to corticosteroids. Of those, 27 experienced clinical improvement, which was defined as documentation of symptom resolution or hospital discharge within 7 days, Aparna Hegde, MD, of East Carolina University, Greenville, N.C., reported at the Chicago Multidisciplinary Symposium in Thoracic Oncology.

The median time to discharge was 4 days, and no adverse effect on median overall survival was seen between those who received tocilizumab and those who did not (6.1 vs, 6.7 months, respectively), Dr. Hegde said.

There was, however, a trend toward inferior overall survival in patients who required more than one dose of tocilizumab, but the difference was not statistically significant (hazard ratio, 1.72), she noted.

“Immune checkpoint inhibitors are associated with an unprecedented clinical benefit in patients with lung cancer. However, they are also associated with a unique spectrum of immune-mediated adverse events. While the standard of care for initial management of these adverse events is corticosteroids, the management of steroid-refractory events is poorly defined,” she said, adding that data from randomized trials on which consensus guidelines could be based are lacking.

At East Carolina University, a significant proportion of patients treated with PD-1 inhibitors were presenting with systemic inflammatory response syndrome (SIRS)-like symptoms and immune-related organ toxicities similar to what has been described in cytokine release syndrome, Dr. Hegde said.

Such symptoms have also been reported with other types of immune therapy, such as CAR T-cell therapy and bispecific T-cell receptor–engaging antibodies in hematologic malignancies, she noted.

“In our experience, when we treated these patients with tocilizumab, which is an [anti-interleukin-6] receptor monoclonal antibody, we saw dramatic and rapid responses, not only in the SIRS symptoms, but also in other immune-related organ toxicities. Therefore, we adopted the use of tocilizumab as our standard treatment for high-grade immune-related adverse events,” she said, explaining that it has been well documented that interleukin (IL)-6 levels increase during cytokine release syndrome and are mediators of inflammation, suggesting that blocking IL-6 may treat irAEs without compromising the efficacy of immune therapy.

The current study was undertaken to look more closely at the responses to tocilizumab and to assess overall survival in those who received tocilizumab.

Study participants were being prospectively followed as part of another ongoing study looking at the relationship between systemic inflammation and cancer-related symptom burden. Most (77) were being treated for lung cancer and 10 had other types of malignancy. They received nivolumab at a dose of 3 mg/kg (or a flat dose of 240 mg after September 2016) every 2 weeks, and received tocilizumab at a dose of 4 mg/kg given over 1 hour. Those with grade 3 or 4 irAEs also received supportive care and corticosteroids. Median follow-up was 10.6 months.

C-reactive protein (CRP), a reliable surrogate marker of IL-6, was drawn at the first nivolumab infusion and before each subsequent infusion as part of the study in which the patients were enrolled, and for the current analysis was measured in relation to irAEs.

Significant reductions were seen in CRP levels after tocilizumab treatment; similar responses have been described in cytokine release syndrome, Dr. Hegde noted.

“Tocilizumab is a therapeutic option for management of immune-related adverse events in patients who are already on corticosteroids. CRP may be of clinical utility in detecting immune-related adverse events as well as monitoring the response to tocilizumab,” she said, adding that the current analysis is limited by the small patient number, single-center setting, use of tocilizumab outside of a clinical trial setting, and short follow-up.

Therefore, the findings require confirmation in multicenter randomized trials to determine “the definitive utility of tocilizumab, as well as CRP as an accompanying biomarker in the management of high-grade steroid refractory immune-related adverse events.”

Heather Wakelee, MD, an invited discussant at the symposium, commended Dr. Hegde and her colleagues for “coming up with a novel idea about how to treat [irAEs],” but also stressed the need for further study.

“This is a novel agent that has the potential ability to manage toxicity, and that’s important, because when you get beyond the steroids that we use as a first-line approach ... there’s not a whole lot else. We definitely have a clear unmet need,” said Dr. Wakelee of Stanford (Calif.) University.

However, she stressed that the approach must be evaluated in multicenter randomized trials “before we can be widely discussing this as a good thing to be doing.”

Dr. Hegde reported having no disclosures. Dr. Wakelee has been the institutional principal investigator for studies of nivolumab, tocilizumab, and other agents. She has consulted for Peregrine, ACEA, Pfizer, Helsinn, Genentech/Roche, Clovis, and Lilly, and received research/grant support from Clovis, Exelixis, AstraZeneca/Medimmune, Genentech/Roche, BMS, Gilead, Novartis, Xcovery, Pfizer, Celgene, Gilead, Pharmacyclics, and Lilly.

[email protected]

CHICAGO – Tocilizumab may be a therapeutic option for steroid-refractory immune-related adverse events that are secondary to PD-1 blockade, according to findings from a review of patients treated with nivolumab for various malignancies.

Of 87 patients who were treated with the PD-1 inhibitor between April 2015 and October 2016, 34 received tocilizumab for high-grade immune-related adverse events (irAEs) that were refractory to corticosteroids. Of those, 27 experienced clinical improvement, which was defined as documentation of symptom resolution or hospital discharge within 7 days, Aparna Hegde, MD, of East Carolina University, Greenville, N.C., reported at the Chicago Multidisciplinary Symposium in Thoracic Oncology.

The median time to discharge was 4 days, and no adverse effect on median overall survival was seen between those who received tocilizumab and those who did not (6.1 vs, 6.7 months, respectively), Dr. Hegde said.

There was, however, a trend toward inferior overall survival in patients who required more than one dose of tocilizumab, but the difference was not statistically significant (hazard ratio, 1.72), she noted.

“Immune checkpoint inhibitors are associated with an unprecedented clinical benefit in patients with lung cancer. However, they are also associated with a unique spectrum of immune-mediated adverse events. While the standard of care for initial management of these adverse events is corticosteroids, the management of steroid-refractory events is poorly defined,” she said, adding that data from randomized trials on which consensus guidelines could be based are lacking.

At East Carolina University, a significant proportion of patients treated with PD-1 inhibitors were presenting with systemic inflammatory response syndrome (SIRS)-like symptoms and immune-related organ toxicities similar to what has been described in cytokine release syndrome, Dr. Hegde said.

Such symptoms have also been reported with other types of immune therapy, such as CAR T-cell therapy and bispecific T-cell receptor–engaging antibodies in hematologic malignancies, she noted.

“In our experience, when we treated these patients with tocilizumab, which is an [anti-interleukin-6] receptor monoclonal antibody, we saw dramatic and rapid responses, not only in the SIRS symptoms, but also in other immune-related organ toxicities. Therefore, we adopted the use of tocilizumab as our standard treatment for high-grade immune-related adverse events,” she said, explaining that it has been well documented that interleukin (IL)-6 levels increase during cytokine release syndrome and are mediators of inflammation, suggesting that blocking IL-6 may treat irAEs without compromising the efficacy of immune therapy.

The current study was undertaken to look more closely at the responses to tocilizumab and to assess overall survival in those who received tocilizumab.

Study participants were being prospectively followed as part of another ongoing study looking at the relationship between systemic inflammation and cancer-related symptom burden. Most (77) were being treated for lung cancer and 10 had other types of malignancy. They received nivolumab at a dose of 3 mg/kg (or a flat dose of 240 mg after September 2016) every 2 weeks, and received tocilizumab at a dose of 4 mg/kg given over 1 hour. Those with grade 3 or 4 irAEs also received supportive care and corticosteroids. Median follow-up was 10.6 months.

C-reactive protein (CRP), a reliable surrogate marker of IL-6, was drawn at the first nivolumab infusion and before each subsequent infusion as part of the study in which the patients were enrolled, and for the current analysis was measured in relation to irAEs.

Significant reductions were seen in CRP levels after tocilizumab treatment; similar responses have been described in cytokine release syndrome, Dr. Hegde noted.

“Tocilizumab is a therapeutic option for management of immune-related adverse events in patients who are already on corticosteroids. CRP may be of clinical utility in detecting immune-related adverse events as well as monitoring the response to tocilizumab,” she said, adding that the current analysis is limited by the small patient number, single-center setting, use of tocilizumab outside of a clinical trial setting, and short follow-up.

Therefore, the findings require confirmation in multicenter randomized trials to determine “the definitive utility of tocilizumab, as well as CRP as an accompanying biomarker in the management of high-grade steroid refractory immune-related adverse events.”

Heather Wakelee, MD, an invited discussant at the symposium, commended Dr. Hegde and her colleagues for “coming up with a novel idea about how to treat [irAEs],” but also stressed the need for further study.

“This is a novel agent that has the potential ability to manage toxicity, and that’s important, because when you get beyond the steroids that we use as a first-line approach ... there’s not a whole lot else. We definitely have a clear unmet need,” said Dr. Wakelee of Stanford (Calif.) University.

However, she stressed that the approach must be evaluated in multicenter randomized trials “before we can be widely discussing this as a good thing to be doing.”

Dr. Hegde reported having no disclosures. Dr. Wakelee has been the institutional principal investigator for studies of nivolumab, tocilizumab, and other agents. She has consulted for Peregrine, ACEA, Pfizer, Helsinn, Genentech/Roche, Clovis, and Lilly, and received research/grant support from Clovis, Exelixis, AstraZeneca/Medimmune, Genentech/Roche, BMS, Gilead, Novartis, Xcovery, Pfizer, Celgene, Gilead, Pharmacyclics, and Lilly.

[email protected]

CHICAGO – Tocilizumab may be a therapeutic option for steroid-refractory immune-related adverse events that are secondary to PD-1 blockade, according to findings from a review of patients treated with nivolumab for various malignancies.

Of 87 patients who were treated with the PD-1 inhibitor between April 2015 and October 2016, 34 received tocilizumab for high-grade immune-related adverse events (irAEs) that were refractory to corticosteroids. Of those, 27 experienced clinical improvement, which was defined as documentation of symptom resolution or hospital discharge within 7 days, Aparna Hegde, MD, of East Carolina University, Greenville, N.C., reported at the Chicago Multidisciplinary Symposium in Thoracic Oncology.

The median time to discharge was 4 days, and no adverse effect on median overall survival was seen between those who received tocilizumab and those who did not (6.1 vs, 6.7 months, respectively), Dr. Hegde said.

There was, however, a trend toward inferior overall survival in patients who required more than one dose of tocilizumab, but the difference was not statistically significant (hazard ratio, 1.72), she noted.

“Immune checkpoint inhibitors are associated with an unprecedented clinical benefit in patients with lung cancer. However, they are also associated with a unique spectrum of immune-mediated adverse events. While the standard of care for initial management of these adverse events is corticosteroids, the management of steroid-refractory events is poorly defined,” she said, adding that data from randomized trials on which consensus guidelines could be based are lacking.

At East Carolina University, a significant proportion of patients treated with PD-1 inhibitors were presenting with systemic inflammatory response syndrome (SIRS)-like symptoms and immune-related organ toxicities similar to what has been described in cytokine release syndrome, Dr. Hegde said.

Such symptoms have also been reported with other types of immune therapy, such as CAR T-cell therapy and bispecific T-cell receptor–engaging antibodies in hematologic malignancies, she noted.

“In our experience, when we treated these patients with tocilizumab, which is an [anti-interleukin-6] receptor monoclonal antibody, we saw dramatic and rapid responses, not only in the SIRS symptoms, but also in other immune-related organ toxicities. Therefore, we adopted the use of tocilizumab as our standard treatment for high-grade immune-related adverse events,” she said, explaining that it has been well documented that interleukin (IL)-6 levels increase during cytokine release syndrome and are mediators of inflammation, suggesting that blocking IL-6 may treat irAEs without compromising the efficacy of immune therapy.

The current study was undertaken to look more closely at the responses to tocilizumab and to assess overall survival in those who received tocilizumab.

Study participants were being prospectively followed as part of another ongoing study looking at the relationship between systemic inflammation and cancer-related symptom burden. Most (77) were being treated for lung cancer and 10 had other types of malignancy. They received nivolumab at a dose of 3 mg/kg (or a flat dose of 240 mg after September 2016) every 2 weeks, and received tocilizumab at a dose of 4 mg/kg given over 1 hour. Those with grade 3 or 4 irAEs also received supportive care and corticosteroids. Median follow-up was 10.6 months.

C-reactive protein (CRP), a reliable surrogate marker of IL-6, was drawn at the first nivolumab infusion and before each subsequent infusion as part of the study in which the patients were enrolled, and for the current analysis was measured in relation to irAEs.

Significant reductions were seen in CRP levels after tocilizumab treatment; similar responses have been described in cytokine release syndrome, Dr. Hegde noted.

“Tocilizumab is a therapeutic option for management of immune-related adverse events in patients who are already on corticosteroids. CRP may be of clinical utility in detecting immune-related adverse events as well as monitoring the response to tocilizumab,” she said, adding that the current analysis is limited by the small patient number, single-center setting, use of tocilizumab outside of a clinical trial setting, and short follow-up.

Therefore, the findings require confirmation in multicenter randomized trials to determine “the definitive utility of tocilizumab, as well as CRP as an accompanying biomarker in the management of high-grade steroid refractory immune-related adverse events.”

Heather Wakelee, MD, an invited discussant at the symposium, commended Dr. Hegde and her colleagues for “coming up with a novel idea about how to treat [irAEs],” but also stressed the need for further study.

“This is a novel agent that has the potential ability to manage toxicity, and that’s important, because when you get beyond the steroids that we use as a first-line approach ... there’s not a whole lot else. We definitely have a clear unmet need,” said Dr. Wakelee of Stanford (Calif.) University.

However, she stressed that the approach must be evaluated in multicenter randomized trials “before we can be widely discussing this as a good thing to be doing.”

Dr. Hegde reported having no disclosures. Dr. Wakelee has been the institutional principal investigator for studies of nivolumab, tocilizumab, and other agents. She has consulted for Peregrine, ACEA, Pfizer, Helsinn, Genentech/Roche, Clovis, and Lilly, and received research/grant support from Clovis, Exelixis, AstraZeneca/Medimmune, Genentech/Roche, BMS, Gilead, Novartis, Xcovery, Pfizer, Celgene, Gilead, Pharmacyclics, and Lilly.

[email protected]

Almost two-thirds of patients with advanced melanoma responded to combination therapy with pembrolizumab and talimogene laherparepvec (T-vec) in a small phase 1b trial, investigators reported.

A third of patients achieved a complete response and median progression-free and overall survival were not reached after typically 18.6 (range, 17.7 to 20.8) months of follow-up, said Antoni Ribas, MD, of the University of California, Los Angeles, and his coinvestigators. In contrast to single-agent pembrolizumab therapy, responders to the combination regimen included patients with very low levels of CD8+ T cell infiltrates or negative interferon-gamma (IFN-gamma) gene signatures in baseline tumor biopsies, suggesting that oncolytic virotherapy might make anti-PD-1 therapy more effective by altering the tumor microenvironment, the researchers concluded. Serious adverse events were uncommon in this study, and there were no dose-limiting toxicities, they wrote (Cell. 2017 Sept. 7 doi: 10.1016/j.cell.2017.08.027).

Courtesy UCLA Jonsson Comprehensive Cancer Center

Almost two-thirds of patients with advanced melanoma responded to combination therapy with pembrolizumab and talimogene laherparepvec (T-vec) in a small phase 1b trial, investigators reported.

A third of patients achieved a complete response and median progression-free and overall survival were not reached after typically 18.6 (range, 17.7 to 20.8) months of follow-up, said Antoni Ribas, MD, of the University of California, Los Angeles, and his coinvestigators. In contrast to single-agent pembrolizumab therapy, responders to the combination regimen included patients with very low levels of CD8+ T cell infiltrates or negative interferon-gamma (IFN-gamma) gene signatures in baseline tumor biopsies, suggesting that oncolytic virotherapy might make anti-PD-1 therapy more effective by altering the tumor microenvironment, the researchers concluded. Serious adverse events were uncommon in this study, and there were no dose-limiting toxicities, they wrote (Cell. 2017 Sept. 7 doi: 10.1016/j.cell.2017.08.027).

Courtesy UCLA Jonsson Comprehensive Cancer Center

Almost two-thirds of patients with advanced melanoma responded to combination therapy with pembrolizumab and talimogene laherparepvec (T-vec) in a small phase 1b trial, investigators reported.

A third of patients achieved a complete response and median progression-free and overall survival were not reached after typically 18.6 (range, 17.7 to 20.8) months of follow-up, said Antoni Ribas, MD, of the University of California, Los Angeles, and his coinvestigators. In contrast to single-agent pembrolizumab therapy, responders to the combination regimen included patients with very low levels of CD8+ T cell infiltrates or negative interferon-gamma (IFN-gamma) gene signatures in baseline tumor biopsies, suggesting that oncolytic virotherapy might make anti-PD-1 therapy more effective by altering the tumor microenvironment, the researchers concluded. Serious adverse events were uncommon in this study, and there were no dose-limiting toxicities, they wrote (Cell. 2017 Sept. 7 doi: 10.1016/j.cell.2017.08.027).

Courtesy UCLA Jonsson Comprehensive Cancer Center