AVAHO

Radiation therapy should be the primary treatment for patients with basal cell carcinoma and cutaneous squamous cell carcinoma who are not candidates for surgery, according to a new guideline from an American Society for Radiation Oncology task force.

“We hope that the dermatology community will find this guideline helpful, especially when it comes to defining clinical and pathological characteristics that may necessitate a discussion about the merits of postoperative radiation therapy,” said lead author Anna Likhacheva, MD, of the Sutter Medical Center in Sacramento, Calif., in an email. The guideline was published in Practical Radiation Oncology.

To address five key questions in regard to radiation therapy (RT) for the two most common skin cancers, the American Society for Radiation Oncology convened a task force of radiation, medical, and surgical oncologists; dermatopathologists; a radiation oncology resident; a medical physicist; and a dermatologist. They reviewed studies of adults with nonmetastatic, invasive basal cell carcinoma (BCC) or cutaneous squamous cell carcinoma (cSCC) that were published between May 1998 and June 2018, with the caveat that “there are limited, well-conducted modern randomized trials” in this area. As such, the majority of the recommendations have low to moderate quality of evidence designations.

“The conspicuous lack of prospective and randomized data should serve as a reminder to open clinical trials and collect outcomes data in a prospective fashion,” added Dr. Likhacheva, noting that “improving the quality of data on this topic will ultimately serve our common goal of improving patient outcomes.”

Their first recommendation was to strongly consider definitive RT as an alternative to surgery for BCC and cSCC, especially in areas where a surgical procedure would potentially compromise function or cosmesis. However, they did discourage its use in patients with genetic conditions associated with increased radiosensitivity.

Their second recommendation was to strongly consider postoperative radiation therapy for clinically or radiologically apparent gross perineural spread. They also strongly recommended PORT for cSCC patients with close or positive margins, with T3 or T4 tumors, or with desmoplastic or infiltrative tumors.

Their third recommendation was to strongly consider therapeutic lymphadenectomy followed by adjuvant RT in patients with cSCC or BCC that has metastasized to the regional lymph nodes. They also recommended definitive RT in medically inoperable patients with the same metastasized cSCC or BCC. In addition, patients with BCC or cSCC undergoing adjuvant RT after therapeutic lymphadenectomy were recommended a dose of 6,000-6,600 cGy, while patients with cSCC undergoing elective RT without a lymphadenectomy were recommended a dose of 5,000-5,400 cGy.

Their fourth recommendation focused on techniques and dose-fractionation schedules for RT in the definitive or postoperative setting. For patients with BCC and cSCC receiving definitive RT, the biologically effective dose (BED₁₀) range for conventional fractionation – defined as 180-200 cGy/fraction – should be 70-93.5 and the BED₁₀ range for hypofractionation – defined as 210-500 cGy/fraction – should be 56-88. For patients with BCC and cSCC receiving postoperative RT, the BED₁₀ range for conventional fractionation should be 59.5-79.2 and the BED₁₀ range for hypofractionation should be 56-70.2.

Finally, their fifth recommendation was to not add concurrent carboplatin to adjuvant RT in patients with resected, locally advanced cSCC. They also conditionally recommended adding concurrent drug therapies to definitive RT in patients with unresected, locally advanced cSCC.

Several of the authors reported receiving honoraria and travel expenses from medical and pharmaceutical companies, along with serving on their advisory boards. The others reported no conflicts of interest.

SOURCE: Likhacheva A et al. Pract Radiat Oncol. 2019 Dec 9. doi: 10.1016/j.prro.2019.10.014.

Radiation therapy should be the primary treatment for patients with basal cell carcinoma and cutaneous squamous cell carcinoma who are not candidates for surgery, according to a new guideline from an American Society for Radiation Oncology task force.

“We hope that the dermatology community will find this guideline helpful, especially when it comes to defining clinical and pathological characteristics that may necessitate a discussion about the merits of postoperative radiation therapy,” said lead author Anna Likhacheva, MD, of the Sutter Medical Center in Sacramento, Calif., in an email. The guideline was published in Practical Radiation Oncology.

To address five key questions in regard to radiation therapy (RT) for the two most common skin cancers, the American Society for Radiation Oncology convened a task force of radiation, medical, and surgical oncologists; dermatopathologists; a radiation oncology resident; a medical physicist; and a dermatologist. They reviewed studies of adults with nonmetastatic, invasive basal cell carcinoma (BCC) or cutaneous squamous cell carcinoma (cSCC) that were published between May 1998 and June 2018, with the caveat that “there are limited, well-conducted modern randomized trials” in this area. As such, the majority of the recommendations have low to moderate quality of evidence designations.

“The conspicuous lack of prospective and randomized data should serve as a reminder to open clinical trials and collect outcomes data in a prospective fashion,” added Dr. Likhacheva, noting that “improving the quality of data on this topic will ultimately serve our common goal of improving patient outcomes.”

Their first recommendation was to strongly consider definitive RT as an alternative to surgery for BCC and cSCC, especially in areas where a surgical procedure would potentially compromise function or cosmesis. However, they did discourage its use in patients with genetic conditions associated with increased radiosensitivity.

Their second recommendation was to strongly consider postoperative radiation therapy for clinically or radiologically apparent gross perineural spread. They also strongly recommended PORT for cSCC patients with close or positive margins, with T3 or T4 tumors, or with desmoplastic or infiltrative tumors.

Their third recommendation was to strongly consider therapeutic lymphadenectomy followed by adjuvant RT in patients with cSCC or BCC that has metastasized to the regional lymph nodes. They also recommended definitive RT in medically inoperable patients with the same metastasized cSCC or BCC. In addition, patients with BCC or cSCC undergoing adjuvant RT after therapeutic lymphadenectomy were recommended a dose of 6,000-6,600 cGy, while patients with cSCC undergoing elective RT without a lymphadenectomy were recommended a dose of 5,000-5,400 cGy.

Their fourth recommendation focused on techniques and dose-fractionation schedules for RT in the definitive or postoperative setting. For patients with BCC and cSCC receiving definitive RT, the biologically effective dose (BED₁₀) range for conventional fractionation – defined as 180-200 cGy/fraction – should be 70-93.5 and the BED₁₀ range for hypofractionation – defined as 210-500 cGy/fraction – should be 56-88. For patients with BCC and cSCC receiving postoperative RT, the BED₁₀ range for conventional fractionation should be 59.5-79.2 and the BED₁₀ range for hypofractionation should be 56-70.2.

Finally, their fifth recommendation was to not add concurrent carboplatin to adjuvant RT in patients with resected, locally advanced cSCC. They also conditionally recommended adding concurrent drug therapies to definitive RT in patients with unresected, locally advanced cSCC.

Several of the authors reported receiving honoraria and travel expenses from medical and pharmaceutical companies, along with serving on their advisory boards. The others reported no conflicts of interest.

SOURCE: Likhacheva A et al. Pract Radiat Oncol. 2019 Dec 9. doi: 10.1016/j.prro.2019.10.014.

Radiation therapy should be the primary treatment for patients with basal cell carcinoma and cutaneous squamous cell carcinoma who are not candidates for surgery, according to a new guideline from an American Society for Radiation Oncology task force.

“We hope that the dermatology community will find this guideline helpful, especially when it comes to defining clinical and pathological characteristics that may necessitate a discussion about the merits of postoperative radiation therapy,” said lead author Anna Likhacheva, MD, of the Sutter Medical Center in Sacramento, Calif., in an email. The guideline was published in Practical Radiation Oncology.

To address five key questions in regard to radiation therapy (RT) for the two most common skin cancers, the American Society for Radiation Oncology convened a task force of radiation, medical, and surgical oncologists; dermatopathologists; a radiation oncology resident; a medical physicist; and a dermatologist. They reviewed studies of adults with nonmetastatic, invasive basal cell carcinoma (BCC) or cutaneous squamous cell carcinoma (cSCC) that were published between May 1998 and June 2018, with the caveat that “there are limited, well-conducted modern randomized trials” in this area. As such, the majority of the recommendations have low to moderate quality of evidence designations.

“The conspicuous lack of prospective and randomized data should serve as a reminder to open clinical trials and collect outcomes data in a prospective fashion,” added Dr. Likhacheva, noting that “improving the quality of data on this topic will ultimately serve our common goal of improving patient outcomes.”

Their first recommendation was to strongly consider definitive RT as an alternative to surgery for BCC and cSCC, especially in areas where a surgical procedure would potentially compromise function or cosmesis. However, they did discourage its use in patients with genetic conditions associated with increased radiosensitivity.

Their second recommendation was to strongly consider postoperative radiation therapy for clinically or radiologically apparent gross perineural spread. They also strongly recommended PORT for cSCC patients with close or positive margins, with T3 or T4 tumors, or with desmoplastic or infiltrative tumors.

Their third recommendation was to strongly consider therapeutic lymphadenectomy followed by adjuvant RT in patients with cSCC or BCC that has metastasized to the regional lymph nodes. They also recommended definitive RT in medically inoperable patients with the same metastasized cSCC or BCC. In addition, patients with BCC or cSCC undergoing adjuvant RT after therapeutic lymphadenectomy were recommended a dose of 6,000-6,600 cGy, while patients with cSCC undergoing elective RT without a lymphadenectomy were recommended a dose of 5,000-5,400 cGy.

Their fourth recommendation focused on techniques and dose-fractionation schedules for RT in the definitive or postoperative setting. For patients with BCC and cSCC receiving definitive RT, the biologically effective dose (BED₁₀) range for conventional fractionation – defined as 180-200 cGy/fraction – should be 70-93.5 and the BED₁₀ range for hypofractionation – defined as 210-500 cGy/fraction – should be 56-88. For patients with BCC and cSCC receiving postoperative RT, the BED₁₀ range for conventional fractionation should be 59.5-79.2 and the BED₁₀ range for hypofractionation should be 56-70.2.

Finally, their fifth recommendation was to not add concurrent carboplatin to adjuvant RT in patients with resected, locally advanced cSCC. They also conditionally recommended adding concurrent drug therapies to definitive RT in patients with unresected, locally advanced cSCC.

Several of the authors reported receiving honoraria and travel expenses from medical and pharmaceutical companies, along with serving on their advisory boards. The others reported no conflicts of interest.

SOURCE: Likhacheva A et al. Pract Radiat Oncol. 2019 Dec 9. doi: 10.1016/j.prro.2019.10.014.

The GO2 Foundation for Lung Cancer has granted the 2019 Young Innovators Team Awards to two groups of investigators studying non-small cell lung cancer (NSCLC). Each group received $250,000 to support their work.

Dr. Guo and Dr. Davidson aim to prove that cancer cell metabolism affects the tumor microenvironment and leads to an impaired antitumor immune response. The pair’s ultimate goal is to overcome resistance to immunotherapy in KRAS-mutant NSCLC.


Matthew Bott, MD, of Memorial Sloan Kettering Cancer Center in New York, and Tuomas Tammela, MD, PhD, of Weill-Cornell Medical College in New York, won the award for their research on age-related differences in NSCLC.

[email protected]

The GO2 Foundation for Lung Cancer has granted the 2019 Young Innovators Team Awards to two groups of investigators studying non-small cell lung cancer (NSCLC). Each group received $250,000 to support their work.

Dr. Guo and Dr. Davidson aim to prove that cancer cell metabolism affects the tumor microenvironment and leads to an impaired antitumor immune response. The pair’s ultimate goal is to overcome resistance to immunotherapy in KRAS-mutant NSCLC.


Matthew Bott, MD, of Memorial Sloan Kettering Cancer Center in New York, and Tuomas Tammela, MD, PhD, of Weill-Cornell Medical College in New York, won the award for their research on age-related differences in NSCLC.

[email protected]

The GO2 Foundation for Lung Cancer has granted the 2019 Young Innovators Team Awards to two groups of investigators studying non-small cell lung cancer (NSCLC). Each group received $250,000 to support their work.

Dr. Guo and Dr. Davidson aim to prove that cancer cell metabolism affects the tumor microenvironment and leads to an impaired antitumor immune response. The pair’s ultimate goal is to overcome resistance to immunotherapy in KRAS-mutant NSCLC.


Matthew Bott, MD, of Memorial Sloan Kettering Cancer Center in New York, and Tuomas Tammela, MD, PhD, of Weill-Cornell Medical College in New York, won the award for their research on age-related differences in NSCLC.

[email protected]

ORLANDO – Updated trial results have revealed durable responses with venetoclax and ibrutinib in patients with mantle cell lymphoma (MCL), allowing some patients to stop treatment.

Jennifer Smith/MDedge News

Five of 24 patients were able to stop treatment after achieving minimal residual disease (MRD)-negative complete responses (CRs). Four of these patients remain in CR at up to 18 months off treatment, although one patient ultimately progressed and died.

“Treatment cessation was feasible for patients in MRD-negative complete responses, raising the prospect of limited-duration, targeted-agent therapy in the management of relapsed/refractory mantle cell lymphoma,” said Sasanka M. Handunnetti, MBBS, of Peter MacCallum Cancer Centre in Melbourne. Dr. Handunnetti presented these results, from the AIM trial, at the annual meeting of the American Society of Hematology.

The phase 2 trial enrolled 24 patients. At baseline, patients had a median age of 68 years (range, 47-81 years), and 88% were men. One patient was treatment-naive, but the rest had relapsed/refractory MCL. These patients had received a median of two prior therapies (range, 1-6).

The patients received venetoclax at 400 mg daily and ibrutinib at 560 mg daily.

In the primary analysis, the CR rate was 62% at week 16 and 71% overall, according to positron-emission tomography/computed tomography. MRD negativity was achieved by 67% of patients according to flow cytometry and 38% according to allele-specific oligonucleotide polymerase chain reaction (N Engl J Med. 2018 Mar 29;378[13]:1211-23).
 

Response and survival

For the current analysis, the median follow up was 37.5 months (range, 1.4-45.3 months). The median duration of response has not been reached, the median progression-free survival is 29 months, and the median overall survival is 32 months.

Thirteen patients have died, 8 of them due to progressive disease. The remaining 11 patients are still alive, and 9 of them are still in CR. One patient is still in partial response, and one has not responded but remains on ibrutinib and venetoclax.

Dr. Handunnetti pointed out that 12 patients had TP53 aberrations, and 8 of them died, but 4 remain alive and in CR. All four patients with SMARCA4 aberrations died.

Treatment status

Five patients are still receiving treatment with ibrutinib and venetoclax, and one patient is receiving only venetoclax. One patient went off study treatment due to a diagnosis of myelodysplastic syndrome, but that patient’s MCL is still in CR.

Five patients were able to stop treatment after achieving MRD-negative CR and were placed under “stringent surveillance,” Dr. Handunnetti said.

One of the five patients who stopped treatment progressed at 7 months and died. The remaining four patients are still alive and in CR at 6 months, 13 months, 17 months, and 18 months off treatment.
 

Safety update

Within the first 56 weeks of treatment, 15 patients required dose adjustments. Twelve patients required an adjustment to ibrutinib, seven to venetoclax, and four to both drugs. After 56 weeks, there were no dose adjustments.

Two patients developed therapy-related myelodysplastic syndrome. One patient had previously received FCR (fludarabine, cyclophosphamide, and rituximab) and BR (bendamustine and rituximab). The other patient had received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).

This investigator-initiated trial was funded by Janssen and Abbvie. Dr. Handunnetti reported relationships with Abbvie and Gilead.

[email protected]

SOURCE: Handunnetti S et al. ASH 2019. Abstract 756.

ORLANDO – Updated trial results have revealed durable responses with venetoclax and ibrutinib in patients with mantle cell lymphoma (MCL), allowing some patients to stop treatment.

Jennifer Smith/MDedge News

Five of 24 patients were able to stop treatment after achieving minimal residual disease (MRD)-negative complete responses (CRs). Four of these patients remain in CR at up to 18 months off treatment, although one patient ultimately progressed and died.

“Treatment cessation was feasible for patients in MRD-negative complete responses, raising the prospect of limited-duration, targeted-agent therapy in the management of relapsed/refractory mantle cell lymphoma,” said Sasanka M. Handunnetti, MBBS, of Peter MacCallum Cancer Centre in Melbourne. Dr. Handunnetti presented these results, from the AIM trial, at the annual meeting of the American Society of Hematology.

The phase 2 trial enrolled 24 patients. At baseline, patients had a median age of 68 years (range, 47-81 years), and 88% were men. One patient was treatment-naive, but the rest had relapsed/refractory MCL. These patients had received a median of two prior therapies (range, 1-6).

The patients received venetoclax at 400 mg daily and ibrutinib at 560 mg daily.

In the primary analysis, the CR rate was 62% at week 16 and 71% overall, according to positron-emission tomography/computed tomography. MRD negativity was achieved by 67% of patients according to flow cytometry and 38% according to allele-specific oligonucleotide polymerase chain reaction (N Engl J Med. 2018 Mar 29;378[13]:1211-23).
 

Response and survival

For the current analysis, the median follow up was 37.5 months (range, 1.4-45.3 months). The median duration of response has not been reached, the median progression-free survival is 29 months, and the median overall survival is 32 months.

Thirteen patients have died, 8 of them due to progressive disease. The remaining 11 patients are still alive, and 9 of them are still in CR. One patient is still in partial response, and one has not responded but remains on ibrutinib and venetoclax.

Dr. Handunnetti pointed out that 12 patients had TP53 aberrations, and 8 of them died, but 4 remain alive and in CR. All four patients with SMARCA4 aberrations died.

Treatment status

Five patients are still receiving treatment with ibrutinib and venetoclax, and one patient is receiving only venetoclax. One patient went off study treatment due to a diagnosis of myelodysplastic syndrome, but that patient’s MCL is still in CR.

Five patients were able to stop treatment after achieving MRD-negative CR and were placed under “stringent surveillance,” Dr. Handunnetti said.

One of the five patients who stopped treatment progressed at 7 months and died. The remaining four patients are still alive and in CR at 6 months, 13 months, 17 months, and 18 months off treatment.
 

Safety update

Within the first 56 weeks of treatment, 15 patients required dose adjustments. Twelve patients required an adjustment to ibrutinib, seven to venetoclax, and four to both drugs. After 56 weeks, there were no dose adjustments.

Two patients developed therapy-related myelodysplastic syndrome. One patient had previously received FCR (fludarabine, cyclophosphamide, and rituximab) and BR (bendamustine and rituximab). The other patient had received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).

This investigator-initiated trial was funded by Janssen and Abbvie. Dr. Handunnetti reported relationships with Abbvie and Gilead.

[email protected]

SOURCE: Handunnetti S et al. ASH 2019. Abstract 756.

ORLANDO – Updated trial results have revealed durable responses with venetoclax and ibrutinib in patients with mantle cell lymphoma (MCL), allowing some patients to stop treatment.

Jennifer Smith/MDedge News

Five of 24 patients were able to stop treatment after achieving minimal residual disease (MRD)-negative complete responses (CRs). Four of these patients remain in CR at up to 18 months off treatment, although one patient ultimately progressed and died.

“Treatment cessation was feasible for patients in MRD-negative complete responses, raising the prospect of limited-duration, targeted-agent therapy in the management of relapsed/refractory mantle cell lymphoma,” said Sasanka M. Handunnetti, MBBS, of Peter MacCallum Cancer Centre in Melbourne. Dr. Handunnetti presented these results, from the AIM trial, at the annual meeting of the American Society of Hematology.

The phase 2 trial enrolled 24 patients. At baseline, patients had a median age of 68 years (range, 47-81 years), and 88% were men. One patient was treatment-naive, but the rest had relapsed/refractory MCL. These patients had received a median of two prior therapies (range, 1-6).

The patients received venetoclax at 400 mg daily and ibrutinib at 560 mg daily.

In the primary analysis, the CR rate was 62% at week 16 and 71% overall, according to positron-emission tomography/computed tomography. MRD negativity was achieved by 67% of patients according to flow cytometry and 38% according to allele-specific oligonucleotide polymerase chain reaction (N Engl J Med. 2018 Mar 29;378[13]:1211-23).
 

Response and survival

For the current analysis, the median follow up was 37.5 months (range, 1.4-45.3 months). The median duration of response has not been reached, the median progression-free survival is 29 months, and the median overall survival is 32 months.

Thirteen patients have died, 8 of them due to progressive disease. The remaining 11 patients are still alive, and 9 of them are still in CR. One patient is still in partial response, and one has not responded but remains on ibrutinib and venetoclax.

Dr. Handunnetti pointed out that 12 patients had TP53 aberrations, and 8 of them died, but 4 remain alive and in CR. All four patients with SMARCA4 aberrations died.

Treatment status

Five patients are still receiving treatment with ibrutinib and venetoclax, and one patient is receiving only venetoclax. One patient went off study treatment due to a diagnosis of myelodysplastic syndrome, but that patient’s MCL is still in CR.

Five patients were able to stop treatment after achieving MRD-negative CR and were placed under “stringent surveillance,” Dr. Handunnetti said.

One of the five patients who stopped treatment progressed at 7 months and died. The remaining four patients are still alive and in CR at 6 months, 13 months, 17 months, and 18 months off treatment.
 

Safety update

Within the first 56 weeks of treatment, 15 patients required dose adjustments. Twelve patients required an adjustment to ibrutinib, seven to venetoclax, and four to both drugs. After 56 weeks, there were no dose adjustments.

Two patients developed therapy-related myelodysplastic syndrome. One patient had previously received FCR (fludarabine, cyclophosphamide, and rituximab) and BR (bendamustine and rituximab). The other patient had received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).

This investigator-initiated trial was funded by Janssen and Abbvie. Dr. Handunnetti reported relationships with Abbvie and Gilead.

[email protected]

SOURCE: Handunnetti S et al. ASH 2019. Abstract 756.

SAN ANTONIO – Adding pembrolizumab to chemotherapy in the neoadjuvant setting increased the likelihood that women with stage III or early node-positive triple-negative breast cancer (TNBC) would have a pathologic complete response and sustained clinical benefit, results of the phase 3 KEYNOTE-522 study showed.

Neil Osterweil/MDedge News

Among 602 patients evaluable in a definitive pathological complete response (pCR) analysis, the pCR rate was 64.8% for those treated with chemotherapy plus pembrolizumab (Keytruda), compared with 51.2% for patients treated with chemotherapy plus placebo, reported Peter Schmid, MD, PhD, from Barts Cancer Institute in London.

“The addition of neoadjuvant pembrolizumab to chemotherapy provided a significant increase in the path CR rate in all patients, but also a larger magnitude of path CR benefit versus chemotherapy alone in patients with higher-risk disease, such as stage III disease or node-positive early triple-negative breast cancer,” he said at the annual San Antonio Breast Cancer Symposium.

The overall pCR results were originally reported at the 2019 annual meeting of the European Society for Medical Oncology. At SABCS 2019, he reported pCR results for specific subgroups in KEYNOTE-522.

Investigators enrolled patients aged 18 years or older with newly diagnosed TNBC of either stage T1cN1-2, or T2-4N0-2 and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients also had to have at least two separate tumor cores from the primary tumor for assessment of programmed death–ligand 1 (PD-L1).

After stratification for nodal status, tumor size, and carboplatin schedule (once weekly or every 3 weeks), patients were randomized to receive either pembrolizumab 200 mg every 3 weeks or placebo plus neoadjuvant carboplatin and paclitaxel for four 3-week cycles, followed by four cycles of chemotherapy with either doxorubicin or epirubicin plus cyclophosphamide (AC or EC). Patients went on to surgery, then received adjuvant therapy for nine cycles with either pembrolizumab at the neoadjuvant dose and schedule or placebo.

At the first preplanned interim analysis for event-free survival (EFS) based on 1,174 patients followed for a median of 15.5 months, events had occurred in 7.4% of patients on pembro/chemo, compared with 11.8% on placebo/chemo, but this difference did not meet the prespecified P value boundary of .000051 for significance, Dr. Schmid acknowledged.

When the investigators looked at pCR by disease stage, however, they saw the following benefits across all stages in the study:

• Stage IIA: 73.1% with pembrolizumab versus 62.1% with placebo, difference 11%.
• Stage IIB: 56.2% versus 48.4%, difference 7.8%.
• Stage IIIA: 66.7% versus 42.1%, difference 24.6%.
• Stage IIIB: 48.6% versus 23.1%, difference 25.6%.

The greatest benefit for the addition of pembrolizumab to chemotherapy appeared to be in the higher disease stages, Dr. Schmid said.

There was also a benefit from pembrolizumab for patients with both node-negative disease (pCR, 64.9% vs. 58.6% in the placebo arm) and node-positive disease (64.8% vs. 44.1%, respectively).

pCR rates were also superior with pembrolizumab versus placebo in patients who were PD-L1 negative, defined as a combined positive score (CPS) less than 1 (45.3% vs. 30.3%), as well as PD-L1–positive patients at each of three cutoff values: CPS 1 or greater (68.9% vs. 54.9%), CPS 10 or greater (77.9% vs. 59.8%), and CPS 20 or greater (81.7% vs. 62.5%).

Interestingly, adding pembrolizumab boosted pCR rates both in patients with exposure to a full planned course of chemotherapy (69.7% vs. 55.3% with placebo) and in those who received less than the full course (51.1% vs. 35.7%).

The most common immune-mediated adverse events with the largest between-group differences involved the thyroid, including hypothyroidism (in 14.9% of patients on pembrolizumab and 5.7% of those on placebo), hyperthyroidism (5.1% vs. 1.8%), and thyroiditis (1.7% vs. 1.0%).

“Immune-mediated adverse events are consistent with the known profiles of each regimen, and there’s no new safety signal, no new safety concern at this point in time,” Dr. Schmid said.

Further follow-up will be needed to determine EFS benefit and long-term safety. Investigators plan to perform additional biomarker analyses, including tumor-infiltrating lymphocytes and BRCA, he added.

“Will the KEYNOTE-522 regimen be the new standard of care if approved?” asked invited discussant Kevin Kalinsky, MD, MS, from Columbia University Irving Medical Center in New York. “These are exciting data, both in pCR and early event-free survival. But there’s a risk: a risk of overtreatment, as well as potentially [serious] toxicity in patients with curable disease.”

“The take-home is that this regimen will likely be practice changing in some patients, and with the absence of having a predictor, the benefit may outweigh the risk most in patients with high clinical risk,” he added.

The study was funded by Merck Sharp & Dohme. Dr. Schmid reported advising/consulting for and receiving honoraria from Merck. Dr. Kalinsky disclosed has disclosed that he receives salary from Array Biopharma, has received fees from various companies (not including Merck), and has contracted research with multiple companies, not including Merck.

SOURCE: Schmid P et al. SABCS 2019, Abstract GS3-03.

SAN ANTONIO – Adding pembrolizumab to chemotherapy in the neoadjuvant setting increased the likelihood that women with stage III or early node-positive triple-negative breast cancer (TNBC) would have a pathologic complete response and sustained clinical benefit, results of the phase 3 KEYNOTE-522 study showed.

Neil Osterweil/MDedge News

Among 602 patients evaluable in a definitive pathological complete response (pCR) analysis, the pCR rate was 64.8% for those treated with chemotherapy plus pembrolizumab (Keytruda), compared with 51.2% for patients treated with chemotherapy plus placebo, reported Peter Schmid, MD, PhD, from Barts Cancer Institute in London.

“The addition of neoadjuvant pembrolizumab to chemotherapy provided a significant increase in the path CR rate in all patients, but also a larger magnitude of path CR benefit versus chemotherapy alone in patients with higher-risk disease, such as stage III disease or node-positive early triple-negative breast cancer,” he said at the annual San Antonio Breast Cancer Symposium.

The overall pCR results were originally reported at the 2019 annual meeting of the European Society for Medical Oncology. At SABCS 2019, he reported pCR results for specific subgroups in KEYNOTE-522.

Investigators enrolled patients aged 18 years or older with newly diagnosed TNBC of either stage T1cN1-2, or T2-4N0-2 and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients also had to have at least two separate tumor cores from the primary tumor for assessment of programmed death–ligand 1 (PD-L1).

After stratification for nodal status, tumor size, and carboplatin schedule (once weekly or every 3 weeks), patients were randomized to receive either pembrolizumab 200 mg every 3 weeks or placebo plus neoadjuvant carboplatin and paclitaxel for four 3-week cycles, followed by four cycles of chemotherapy with either doxorubicin or epirubicin plus cyclophosphamide (AC or EC). Patients went on to surgery, then received adjuvant therapy for nine cycles with either pembrolizumab at the neoadjuvant dose and schedule or placebo.

At the first preplanned interim analysis for event-free survival (EFS) based on 1,174 patients followed for a median of 15.5 months, events had occurred in 7.4% of patients on pembro/chemo, compared with 11.8% on placebo/chemo, but this difference did not meet the prespecified P value boundary of .000051 for significance, Dr. Schmid acknowledged.

When the investigators looked at pCR by disease stage, however, they saw the following benefits across all stages in the study:

• Stage IIA: 73.1% with pembrolizumab versus 62.1% with placebo, difference 11%.
• Stage IIB: 56.2% versus 48.4%, difference 7.8%.
• Stage IIIA: 66.7% versus 42.1%, difference 24.6%.
• Stage IIIB: 48.6% versus 23.1%, difference 25.6%.

The greatest benefit for the addition of pembrolizumab to chemotherapy appeared to be in the higher disease stages, Dr. Schmid said.

There was also a benefit from pembrolizumab for patients with both node-negative disease (pCR, 64.9% vs. 58.6% in the placebo arm) and node-positive disease (64.8% vs. 44.1%, respectively).

pCR rates were also superior with pembrolizumab versus placebo in patients who were PD-L1 negative, defined as a combined positive score (CPS) less than 1 (45.3% vs. 30.3%), as well as PD-L1–positive patients at each of three cutoff values: CPS 1 or greater (68.9% vs. 54.9%), CPS 10 or greater (77.9% vs. 59.8%), and CPS 20 or greater (81.7% vs. 62.5%).

Interestingly, adding pembrolizumab boosted pCR rates both in patients with exposure to a full planned course of chemotherapy (69.7% vs. 55.3% with placebo) and in those who received less than the full course (51.1% vs. 35.7%).

The most common immune-mediated adverse events with the largest between-group differences involved the thyroid, including hypothyroidism (in 14.9% of patients on pembrolizumab and 5.7% of those on placebo), hyperthyroidism (5.1% vs. 1.8%), and thyroiditis (1.7% vs. 1.0%).

“Immune-mediated adverse events are consistent with the known profiles of each regimen, and there’s no new safety signal, no new safety concern at this point in time,” Dr. Schmid said.

Further follow-up will be needed to determine EFS benefit and long-term safety. Investigators plan to perform additional biomarker analyses, including tumor-infiltrating lymphocytes and BRCA, he added.

“Will the KEYNOTE-522 regimen be the new standard of care if approved?” asked invited discussant Kevin Kalinsky, MD, MS, from Columbia University Irving Medical Center in New York. “These are exciting data, both in pCR and early event-free survival. But there’s a risk: a risk of overtreatment, as well as potentially [serious] toxicity in patients with curable disease.”

“The take-home is that this regimen will likely be practice changing in some patients, and with the absence of having a predictor, the benefit may outweigh the risk most in patients with high clinical risk,” he added.

The study was funded by Merck Sharp & Dohme. Dr. Schmid reported advising/consulting for and receiving honoraria from Merck. Dr. Kalinsky disclosed has disclosed that he receives salary from Array Biopharma, has received fees from various companies (not including Merck), and has contracted research with multiple companies, not including Merck.

SOURCE: Schmid P et al. SABCS 2019, Abstract GS3-03.

SAN ANTONIO – Adding pembrolizumab to chemotherapy in the neoadjuvant setting increased the likelihood that women with stage III or early node-positive triple-negative breast cancer (TNBC) would have a pathologic complete response and sustained clinical benefit, results of the phase 3 KEYNOTE-522 study showed.

Neil Osterweil/MDedge News

Among 602 patients evaluable in a definitive pathological complete response (pCR) analysis, the pCR rate was 64.8% for those treated with chemotherapy plus pembrolizumab (Keytruda), compared with 51.2% for patients treated with chemotherapy plus placebo, reported Peter Schmid, MD, PhD, from Barts Cancer Institute in London.

“The addition of neoadjuvant pembrolizumab to chemotherapy provided a significant increase in the path CR rate in all patients, but also a larger magnitude of path CR benefit versus chemotherapy alone in patients with higher-risk disease, such as stage III disease or node-positive early triple-negative breast cancer,” he said at the annual San Antonio Breast Cancer Symposium.

The overall pCR results were originally reported at the 2019 annual meeting of the European Society for Medical Oncology. At SABCS 2019, he reported pCR results for specific subgroups in KEYNOTE-522.

Investigators enrolled patients aged 18 years or older with newly diagnosed TNBC of either stage T1cN1-2, or T2-4N0-2 and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients also had to have at least two separate tumor cores from the primary tumor for assessment of programmed death–ligand 1 (PD-L1).

After stratification for nodal status, tumor size, and carboplatin schedule (once weekly or every 3 weeks), patients were randomized to receive either pembrolizumab 200 mg every 3 weeks or placebo plus neoadjuvant carboplatin and paclitaxel for four 3-week cycles, followed by four cycles of chemotherapy with either doxorubicin or epirubicin plus cyclophosphamide (AC or EC). Patients went on to surgery, then received adjuvant therapy for nine cycles with either pembrolizumab at the neoadjuvant dose and schedule or placebo.

At the first preplanned interim analysis for event-free survival (EFS) based on 1,174 patients followed for a median of 15.5 months, events had occurred in 7.4% of patients on pembro/chemo, compared with 11.8% on placebo/chemo, but this difference did not meet the prespecified P value boundary of .000051 for significance, Dr. Schmid acknowledged.

When the investigators looked at pCR by disease stage, however, they saw the following benefits across all stages in the study:

• Stage IIA: 73.1% with pembrolizumab versus 62.1% with placebo, difference 11%.
• Stage IIB: 56.2% versus 48.4%, difference 7.8%.
• Stage IIIA: 66.7% versus 42.1%, difference 24.6%.
• Stage IIIB: 48.6% versus 23.1%, difference 25.6%.

The greatest benefit for the addition of pembrolizumab to chemotherapy appeared to be in the higher disease stages, Dr. Schmid said.

There was also a benefit from pembrolizumab for patients with both node-negative disease (pCR, 64.9% vs. 58.6% in the placebo arm) and node-positive disease (64.8% vs. 44.1%, respectively).

pCR rates were also superior with pembrolizumab versus placebo in patients who were PD-L1 negative, defined as a combined positive score (CPS) less than 1 (45.3% vs. 30.3%), as well as PD-L1–positive patients at each of three cutoff values: CPS 1 or greater (68.9% vs. 54.9%), CPS 10 or greater (77.9% vs. 59.8%), and CPS 20 or greater (81.7% vs. 62.5%).

Interestingly, adding pembrolizumab boosted pCR rates both in patients with exposure to a full planned course of chemotherapy (69.7% vs. 55.3% with placebo) and in those who received less than the full course (51.1% vs. 35.7%).

The most common immune-mediated adverse events with the largest between-group differences involved the thyroid, including hypothyroidism (in 14.9% of patients on pembrolizumab and 5.7% of those on placebo), hyperthyroidism (5.1% vs. 1.8%), and thyroiditis (1.7% vs. 1.0%).

“Immune-mediated adverse events are consistent with the known profiles of each regimen, and there’s no new safety signal, no new safety concern at this point in time,” Dr. Schmid said.

Further follow-up will be needed to determine EFS benefit and long-term safety. Investigators plan to perform additional biomarker analyses, including tumor-infiltrating lymphocytes and BRCA, he added.

“Will the KEYNOTE-522 regimen be the new standard of care if approved?” asked invited discussant Kevin Kalinsky, MD, MS, from Columbia University Irving Medical Center in New York. “These are exciting data, both in pCR and early event-free survival. But there’s a risk: a risk of overtreatment, as well as potentially [serious] toxicity in patients with curable disease.”

“The take-home is that this regimen will likely be practice changing in some patients, and with the absence of having a predictor, the benefit may outweigh the risk most in patients with high clinical risk,” he added.

The study was funded by Merck Sharp & Dohme. Dr. Schmid reported advising/consulting for and receiving honoraria from Merck. Dr. Kalinsky disclosed has disclosed that he receives salary from Array Biopharma, has received fees from various companies (not including Merck), and has contracted research with multiple companies, not including Merck.

SOURCE: Schmid P et al. SABCS 2019, Abstract GS3-03.

SAN ANTONIO – For patients with early, low-risk breast cancer, accelerated partial breast irradiation (APBI) may be considered a standard alternative to whole breast irradiation, according to investigators.

Will Pass/MDedge News

This conclusion was based on 10-year follow-up results from the APBI IMRT Florence phase III trial, which showed that APBI was associated with significantly fewer adverse events and better cosmetic results than whole breast irradiation without increasing risks of tumor recurrence or mortality, reported lead author Irco Meattini, MD, of the University of Florence, Italy, and colleagues.

“As we well know, recent developments in radiation oncology ... show a move toward a deescalation strategy for early breast cancer, including accelerated and nonaccelerated partial breast irradiation,” Dr. Meattini said during a presentation at the San Antonio Breast Cancer Symposium. “What we have learned from [previous] phase 3 trials [is that with adequate patient selection for] partial breast irradiation, safety profile and cosmetic outcome are strongly associated with technique – the approach, the dose, the number of fractions per day, and the total dose.”

The current phase 3 trial, which enrolled 520 patients with early breast cancer, aimed to determine long-term efficacy, safety, and cosmetic outcomes for partial versus whole breast irradiation. All patients enrolled were at least 40 years of age and had a maximum pathological tumor size of 25 mm. Patients were randomized in a 1:1 ratio to receive either whole breast irradiation (WBI) at a dose of 50 Gy in 25 fractions, followed by 10 Gy in five fractions delivered to the tumor bed; or APBI, which was delivered to the tumor bed at a dose of 30 Gy in five daily fractions.

The primary endpoint was ipsilateral breast tumor recurrence (IBTR). Secondary endpoints were overall survival, breast cancer–specific survival, distant metastasis-free survival, locoregional recurrences, and contralateral breast cancer. Adverse events and cosmesis also were evaluated.

Five-year results, previously reported, revealed no significant difference in survival rates or IBTR between treatment techniques, and results of the present 10-year analysis maintained these findings. Between groups, no significant differences were observed in any of the primary or secondary endpoints, suggesting that major efficacy outcomes were unaffected by type of irradiation delivered.

While major efficacy endpoints were comparable between groups, safety profiles and cosmetic results differed significantly.

Adverse events of all levels of severity were significantly more common with WBI than APBI. Grade 2 or higher acute adverse events occurred in 37.7% of patients treated with WBI, compared with just 2.0% of patients treated with APBI (P = .0001). The rate of grade 2 or higher adverse events was also significantly higher in the WBI group than in the APBI group in the late setting, albeit with a narrower margin than in the acute setting (2.7% vs 0%; P = .015). Skin toxicity rates followed a similar pattern, favoring APBI both in the acute phase (66.5% vs. 21.1%; P = .0001) and the late phase (30.0% vs. 4.5%; P = .0001).

In further support of APBI, cosmetic results, as measured by the Harvard Breast Cosmesis Scale, were significantly better in the APBI group than in the WBI group. Both physicians and patients were significantly more likely to report good or excellent cosmetic results with APBI than WBI.

“APBI might be considered a standard alternative to WBI in low risk and very low risk early breast cancer patients,” Dr. Meattini concluded.

The investigators reported no disclosures.

SOURCE: Meattini et al. SABCS. 2019 Dec 12. Abstract GS4-06.

SAN ANTONIO – For patients with early, low-risk breast cancer, accelerated partial breast irradiation (APBI) may be considered a standard alternative to whole breast irradiation, according to investigators.

Will Pass/MDedge News

This conclusion was based on 10-year follow-up results from the APBI IMRT Florence phase III trial, which showed that APBI was associated with significantly fewer adverse events and better cosmetic results than whole breast irradiation without increasing risks of tumor recurrence or mortality, reported lead author Irco Meattini, MD, of the University of Florence, Italy, and colleagues.

“As we well know, recent developments in radiation oncology ... show a move toward a deescalation strategy for early breast cancer, including accelerated and nonaccelerated partial breast irradiation,” Dr. Meattini said during a presentation at the San Antonio Breast Cancer Symposium. “What we have learned from [previous] phase 3 trials [is that with adequate patient selection for] partial breast irradiation, safety profile and cosmetic outcome are strongly associated with technique – the approach, the dose, the number of fractions per day, and the total dose.”

The current phase 3 trial, which enrolled 520 patients with early breast cancer, aimed to determine long-term efficacy, safety, and cosmetic outcomes for partial versus whole breast irradiation. All patients enrolled were at least 40 years of age and had a maximum pathological tumor size of 25 mm. Patients were randomized in a 1:1 ratio to receive either whole breast irradiation (WBI) at a dose of 50 Gy in 25 fractions, followed by 10 Gy in five fractions delivered to the tumor bed; or APBI, which was delivered to the tumor bed at a dose of 30 Gy in five daily fractions.

The primary endpoint was ipsilateral breast tumor recurrence (IBTR). Secondary endpoints were overall survival, breast cancer–specific survival, distant metastasis-free survival, locoregional recurrences, and contralateral breast cancer. Adverse events and cosmesis also were evaluated.

Five-year results, previously reported, revealed no significant difference in survival rates or IBTR between treatment techniques, and results of the present 10-year analysis maintained these findings. Between groups, no significant differences were observed in any of the primary or secondary endpoints, suggesting that major efficacy outcomes were unaffected by type of irradiation delivered.

While major efficacy endpoints were comparable between groups, safety profiles and cosmetic results differed significantly.

Adverse events of all levels of severity were significantly more common with WBI than APBI. Grade 2 or higher acute adverse events occurred in 37.7% of patients treated with WBI, compared with just 2.0% of patients treated with APBI (P = .0001). The rate of grade 2 or higher adverse events was also significantly higher in the WBI group than in the APBI group in the late setting, albeit with a narrower margin than in the acute setting (2.7% vs 0%; P = .015). Skin toxicity rates followed a similar pattern, favoring APBI both in the acute phase (66.5% vs. 21.1%; P = .0001) and the late phase (30.0% vs. 4.5%; P = .0001).

In further support of APBI, cosmetic results, as measured by the Harvard Breast Cosmesis Scale, were significantly better in the APBI group than in the WBI group. Both physicians and patients were significantly more likely to report good or excellent cosmetic results with APBI than WBI.

“APBI might be considered a standard alternative to WBI in low risk and very low risk early breast cancer patients,” Dr. Meattini concluded.

The investigators reported no disclosures.

SOURCE: Meattini et al. SABCS. 2019 Dec 12. Abstract GS4-06.

SAN ANTONIO – For patients with early, low-risk breast cancer, accelerated partial breast irradiation (APBI) may be considered a standard alternative to whole breast irradiation, according to investigators.

Will Pass/MDedge News

This conclusion was based on 10-year follow-up results from the APBI IMRT Florence phase III trial, which showed that APBI was associated with significantly fewer adverse events and better cosmetic results than whole breast irradiation without increasing risks of tumor recurrence or mortality, reported lead author Irco Meattini, MD, of the University of Florence, Italy, and colleagues.

“As we well know, recent developments in radiation oncology ... show a move toward a deescalation strategy for early breast cancer, including accelerated and nonaccelerated partial breast irradiation,” Dr. Meattini said during a presentation at the San Antonio Breast Cancer Symposium. “What we have learned from [previous] phase 3 trials [is that with adequate patient selection for] partial breast irradiation, safety profile and cosmetic outcome are strongly associated with technique – the approach, the dose, the number of fractions per day, and the total dose.”

The current phase 3 trial, which enrolled 520 patients with early breast cancer, aimed to determine long-term efficacy, safety, and cosmetic outcomes for partial versus whole breast irradiation. All patients enrolled were at least 40 years of age and had a maximum pathological tumor size of 25 mm. Patients were randomized in a 1:1 ratio to receive either whole breast irradiation (WBI) at a dose of 50 Gy in 25 fractions, followed by 10 Gy in five fractions delivered to the tumor bed; or APBI, which was delivered to the tumor bed at a dose of 30 Gy in five daily fractions.

The primary endpoint was ipsilateral breast tumor recurrence (IBTR). Secondary endpoints were overall survival, breast cancer–specific survival, distant metastasis-free survival, locoregional recurrences, and contralateral breast cancer. Adverse events and cosmesis also were evaluated.

Five-year results, previously reported, revealed no significant difference in survival rates or IBTR between treatment techniques, and results of the present 10-year analysis maintained these findings. Between groups, no significant differences were observed in any of the primary or secondary endpoints, suggesting that major efficacy outcomes were unaffected by type of irradiation delivered.

While major efficacy endpoints were comparable between groups, safety profiles and cosmetic results differed significantly.

Adverse events of all levels of severity were significantly more common with WBI than APBI. Grade 2 or higher acute adverse events occurred in 37.7% of patients treated with WBI, compared with just 2.0% of patients treated with APBI (P = .0001). The rate of grade 2 or higher adverse events was also significantly higher in the WBI group than in the APBI group in the late setting, albeit with a narrower margin than in the acute setting (2.7% vs 0%; P = .015). Skin toxicity rates followed a similar pattern, favoring APBI both in the acute phase (66.5% vs. 21.1%; P = .0001) and the late phase (30.0% vs. 4.5%; P = .0001).

In further support of APBI, cosmetic results, as measured by the Harvard Breast Cosmesis Scale, were significantly better in the APBI group than in the WBI group. Both physicians and patients were significantly more likely to report good or excellent cosmetic results with APBI than WBI.

“APBI might be considered a standard alternative to WBI in low risk and very low risk early breast cancer patients,” Dr. Meattini concluded.

The investigators reported no disclosures.

SOURCE: Meattini et al. SABCS. 2019 Dec 12. Abstract GS4-06.

SAN ANTONIO – The American Cancer Society’s 2018 qualified recommendation to lower the starting age for colorectal cancer screening from 50 to 45 years in average-risk individuals has picked up new support from a New Hampshire Colonoscopy Registry analysis.

Data from the population-based statewide colonoscopy registry demonstrated that the prevalence of both advanced adenomas and clinically significant serrated polyps was closely similar for average-risk New Hampshirites age 45-49 years and for those age 50-54, Lynn F. Butterly, MD, reported at the annual meeting of the American College of Gastroenterology.

“The clinical implication is that our data support the recommendation to begin average-risk colorectal cancer screening at age 45,” declared Dr. Butterly, a gastroenterologist at Dartmouth-Hitchcock Medical Center in Lebanon, N.H.

The American Cancer Society recommendation to lower the initial screening age was designed to address a disturbing national trend: the climbing incidence of colorectal cancer in young adults. Indeed, the incidence increased by 55% among 20- to 49-year-olds during 1995-2016, even while falling by 38% in individuals age 50 years and older. The 2018 recommendation was billed as “qualified” because it was based upon predictive modeling and National Cancer Institute Surveillance, Epidemiology, and End Results data which have been criticized as subject to potential bias. Several studies conducted in Korea and other Asian countries have reported a lower colorectal cancer risk in the younger adult population than in those age 50 or older, but questions have been raised about the applicability of such data to the U.S. population.

For Dr. Butterly and coinvestigators, the research imperative was clear: “We need to generate U.S. outcomes data for average-risk individuals age 45-49, versus those over age 50, for whom colorectal cancer screening is already strongly recommended.”

Toward that end, the investigators turned to the New Hampshire Colonoscopy Registry, which contains detailed data on 200,000 colonoscopies, with some 400 variables recorded per patient. To zero in on an average-risk population below age 50, they restricted the analysis to patients undergoing their first colonoscopy for evaluation of low-risk conditions including abdominal pain or constipation while excluding those with GI bleeding, iron-deficiency anemia, abnormal imaging, or a family history of colorectal cancer.

The final study population included 42,600 New Hampshire residents who underwent their first colonoscopy. The key outcomes were the prevalence of advanced adenomas, defined as adenomas more than 1 cm in size, or with high-grade dysplasia or villous elements, and the prevalence of clinically significant serrated polyps larger than 1 cm, or larger than 5 mm if proximally located, as well as traditional serrated adenomas and those with sessile features.

The prevalence of advanced adenomas in 1,870 average-risk patients aged 45-49 years was 3.7% and nearly identical at 3.6% in 22,160 individuals undergoing screening colonoscopy at age 50-54. The rate of clinically significant serrated polyps was 5.9% in the 45- to 49-year-olds, closely similar to the 6.1% rate in patients age 50-54.

Of note, the prevalence of advanced adenomas was just 1.1% in individuals younger than age 40 years, jumping to 3.0% among 40- to 44-year-olds, 5.1% in those age 55-59, and 6.9% at age 60 or more. Clinically significant serrated polyps followed a similar pattern, with rates of 3.0% before age 40, 5.1% in 40- to 44-year-olds, 6.6% in 55- to 59-year-olds, and 6.0% in those who were older.

In a multivariate logistic regression analysis adjusted for sex, body mass index, smoking, and other potential confounders, 45- to 49-year-olds were at a 243% increased risk of finding advanced adenomas on colonoscopy, compared with those less than 40 years old, while the 50- to 54-year-olds had a virtually identical 244% increased risk.

Dr. Butterly noted that there are now 15,000 cases of colorectal cancer occurring annually in individuals under age 50 in the United States, with 3,600 deaths.

“Prevention of colorectal cancer in young, productive individuals is an essential clinical imperative that must be addressed,” she concluded.

She reported having no financial conflicts regarding her study.

[email protected]

SAN ANTONIO – The American Cancer Society’s 2018 qualified recommendation to lower the starting age for colorectal cancer screening from 50 to 45 years in average-risk individuals has picked up new support from a New Hampshire Colonoscopy Registry analysis.

Data from the population-based statewide colonoscopy registry demonstrated that the prevalence of both advanced adenomas and clinically significant serrated polyps was closely similar for average-risk New Hampshirites age 45-49 years and for those age 50-54, Lynn F. Butterly, MD, reported at the annual meeting of the American College of Gastroenterology.

“The clinical implication is that our data support the recommendation to begin average-risk colorectal cancer screening at age 45,” declared Dr. Butterly, a gastroenterologist at Dartmouth-Hitchcock Medical Center in Lebanon, N.H.

The American Cancer Society recommendation to lower the initial screening age was designed to address a disturbing national trend: the climbing incidence of colorectal cancer in young adults. Indeed, the incidence increased by 55% among 20- to 49-year-olds during 1995-2016, even while falling by 38% in individuals age 50 years and older. The 2018 recommendation was billed as “qualified” because it was based upon predictive modeling and National Cancer Institute Surveillance, Epidemiology, and End Results data which have been criticized as subject to potential bias. Several studies conducted in Korea and other Asian countries have reported a lower colorectal cancer risk in the younger adult population than in those age 50 or older, but questions have been raised about the applicability of such data to the U.S. population.

For Dr. Butterly and coinvestigators, the research imperative was clear: “We need to generate U.S. outcomes data for average-risk individuals age 45-49, versus those over age 50, for whom colorectal cancer screening is already strongly recommended.”

Toward that end, the investigators turned to the New Hampshire Colonoscopy Registry, which contains detailed data on 200,000 colonoscopies, with some 400 variables recorded per patient. To zero in on an average-risk population below age 50, they restricted the analysis to patients undergoing their first colonoscopy for evaluation of low-risk conditions including abdominal pain or constipation while excluding those with GI bleeding, iron-deficiency anemia, abnormal imaging, or a family history of colorectal cancer.

The final study population included 42,600 New Hampshire residents who underwent their first colonoscopy. The key outcomes were the prevalence of advanced adenomas, defined as adenomas more than 1 cm in size, or with high-grade dysplasia or villous elements, and the prevalence of clinically significant serrated polyps larger than 1 cm, or larger than 5 mm if proximally located, as well as traditional serrated adenomas and those with sessile features.

The prevalence of advanced adenomas in 1,870 average-risk patients aged 45-49 years was 3.7% and nearly identical at 3.6% in 22,160 individuals undergoing screening colonoscopy at age 50-54. The rate of clinically significant serrated polyps was 5.9% in the 45- to 49-year-olds, closely similar to the 6.1% rate in patients age 50-54.

Of note, the prevalence of advanced adenomas was just 1.1% in individuals younger than age 40 years, jumping to 3.0% among 40- to 44-year-olds, 5.1% in those age 55-59, and 6.9% at age 60 or more. Clinically significant serrated polyps followed a similar pattern, with rates of 3.0% before age 40, 5.1% in 40- to 44-year-olds, 6.6% in 55- to 59-year-olds, and 6.0% in those who were older.

In a multivariate logistic regression analysis adjusted for sex, body mass index, smoking, and other potential confounders, 45- to 49-year-olds were at a 243% increased risk of finding advanced adenomas on colonoscopy, compared with those less than 40 years old, while the 50- to 54-year-olds had a virtually identical 244% increased risk.

Dr. Butterly noted that there are now 15,000 cases of colorectal cancer occurring annually in individuals under age 50 in the United States, with 3,600 deaths.

“Prevention of colorectal cancer in young, productive individuals is an essential clinical imperative that must be addressed,” she concluded.

She reported having no financial conflicts regarding her study.

[email protected]

SAN ANTONIO – The American Cancer Society’s 2018 qualified recommendation to lower the starting age for colorectal cancer screening from 50 to 45 years in average-risk individuals has picked up new support from a New Hampshire Colonoscopy Registry analysis.

Data from the population-based statewide colonoscopy registry demonstrated that the prevalence of both advanced adenomas and clinically significant serrated polyps was closely similar for average-risk New Hampshirites age 45-49 years and for those age 50-54, Lynn F. Butterly, MD, reported at the annual meeting of the American College of Gastroenterology.

“The clinical implication is that our data support the recommendation to begin average-risk colorectal cancer screening at age 45,” declared Dr. Butterly, a gastroenterologist at Dartmouth-Hitchcock Medical Center in Lebanon, N.H.

The American Cancer Society recommendation to lower the initial screening age was designed to address a disturbing national trend: the climbing incidence of colorectal cancer in young adults. Indeed, the incidence increased by 55% among 20- to 49-year-olds during 1995-2016, even while falling by 38% in individuals age 50 years and older. The 2018 recommendation was billed as “qualified” because it was based upon predictive modeling and National Cancer Institute Surveillance, Epidemiology, and End Results data which have been criticized as subject to potential bias. Several studies conducted in Korea and other Asian countries have reported a lower colorectal cancer risk in the younger adult population than in those age 50 or older, but questions have been raised about the applicability of such data to the U.S. population.

For Dr. Butterly and coinvestigators, the research imperative was clear: “We need to generate U.S. outcomes data for average-risk individuals age 45-49, versus those over age 50, for whom colorectal cancer screening is already strongly recommended.”

Toward that end, the investigators turned to the New Hampshire Colonoscopy Registry, which contains detailed data on 200,000 colonoscopies, with some 400 variables recorded per patient. To zero in on an average-risk population below age 50, they restricted the analysis to patients undergoing their first colonoscopy for evaluation of low-risk conditions including abdominal pain or constipation while excluding those with GI bleeding, iron-deficiency anemia, abnormal imaging, or a family history of colorectal cancer.

The final study population included 42,600 New Hampshire residents who underwent their first colonoscopy. The key outcomes were the prevalence of advanced adenomas, defined as adenomas more than 1 cm in size, or with high-grade dysplasia or villous elements, and the prevalence of clinically significant serrated polyps larger than 1 cm, or larger than 5 mm if proximally located, as well as traditional serrated adenomas and those with sessile features.

The prevalence of advanced adenomas in 1,870 average-risk patients aged 45-49 years was 3.7% and nearly identical at 3.6% in 22,160 individuals undergoing screening colonoscopy at age 50-54. The rate of clinically significant serrated polyps was 5.9% in the 45- to 49-year-olds, closely similar to the 6.1% rate in patients age 50-54.

Of note, the prevalence of advanced adenomas was just 1.1% in individuals younger than age 40 years, jumping to 3.0% among 40- to 44-year-olds, 5.1% in those age 55-59, and 6.9% at age 60 or more. Clinically significant serrated polyps followed a similar pattern, with rates of 3.0% before age 40, 5.1% in 40- to 44-year-olds, 6.6% in 55- to 59-year-olds, and 6.0% in those who were older.

In a multivariate logistic regression analysis adjusted for sex, body mass index, smoking, and other potential confounders, 45- to 49-year-olds were at a 243% increased risk of finding advanced adenomas on colonoscopy, compared with those less than 40 years old, while the 50- to 54-year-olds had a virtually identical 244% increased risk.

Dr. Butterly noted that there are now 15,000 cases of colorectal cancer occurring annually in individuals under age 50 in the United States, with 3,600 deaths.

“Prevention of colorectal cancer in young, productive individuals is an essential clinical imperative that must be addressed,” she concluded.

She reported having no financial conflicts regarding her study.

[email protected]

ORLANDO – For a patient with chronic lymphocytic leukemia (CLL) who has discontinued venetoclax, choosing the best next therapy may depend on what novel agents the patient was exposed to and why they discontinued them, according to Anthony R. Mato, MD, with the Center for CLL at Memorial Sloan Kettering Cancer Center in New York.

Andrew D. Bowser/MDedge News

If the patient is Bruton tyrosine kinase (BTK) inhibitor naive, then use of a BTK inhibitor after venetoclax would be supported, Dr. Mato said, by the high overall response rates and durable remissions that he and his coinvestigators documented in a retrospective, multicenter study designed specifically to address the gap in knowledge regarding what to use after venetoclax.

If the patient is BTK inhibitor exposed, then the reason for discontinuation needs to be considered before going with that venetoclax-to-BTK inhibitor sequence, Dr. Mato said during an oral presentation at the annual meeting of the American Society of Hematology.

“In patients with resistance to a BTK inhibitor, the sequence was not supported – it did not appear to be effective,” he said. “However, in the setting of intolerance, an alternate BTK inhibitor could be considered.”

The study did not support a venetoclax-to-PI3K inhibitor sequence in PI3K-naive patients, he added, noting that remissions did not appear to be durable, suggesting a potential overlap in resistance mechanisms between agents.

All told, the most effective therapies for in the postvenetoclax setting included the use of a BTK inhibitor in BTK inhibitor–naive or previously responsive patients, and allogeneic transplant following double novel-agent exposure.

“These data may provide support for venetoclax’s earlier use in the course of CLL, and may guide clinical practice and aid in the design of future clinical trials to address sequencing of novel agents,” Dr. Mato told attendees.

While prospective and real-world data clearly show that venetoclax is active in ibrutinib- or idelalisib-exposed patients, data are conversely “variable and limited” with regard to outcomes for next therapies following venetoclax.

“Current data addressing this key sequencing question, I feel, is a major limitation in supporting the sequence of venetoclax to a BTK inhibitor,” Dr. Mato said.

Accordingly, Dr. Mato and colleagues at 31 centers internationally planned and conducted this study, which included data on 326 patients treated with venetoclax who then discontinued for any reason.

“I wanted to highlight that 50% of the sites for this trial were recruited by a single tweet,” said Dr. Mato, adding that he and his coauthors received no funding to conduct this study and volunteered their time to complete it.

They found that, in BTK inhibitor–naive patients who discontinued venetoclax, subsequent BTK inhibitor treatment was associated with a high overall response rate and durable remissions, with a median progression-free survival (PFS) of 32 months.

In BTK inhibitor–exposed patients, response to postvenetoclax BTK inhibitor treatment depended on the reason for discontinuation, with a favorable result (PFS not reached with a mean follow-up of 7.7 months) in patients who were intolerant of the prior BTK inhibitor. By contrast, median PFS was only about 4 months for patients who were resistant to the prior BTK inhibitor.

PI3K inhibitors did not produce durable remissions after venetoclax, with a median PFS also of just 4 months, Dr. Mato reported.

However, cellular therapies appeared to be effective after venetoclax. Allogeneic hematopoietic stem cell transplantation was particularly effective, with the median PFS not reached, while chimeric antigen receptor T-cell therapy produced a PFS of 9 months.

Dr. Mato emphasized that the results of the retrospective trial were “hypothesis generating” and noted that patients in the study had received a median of 3, and up to 11, prior therapies. “This population are probably not our patients receiving venetoclax in clinical practice. They’re more heavily pretreated.”

Dr. Mato reported disclosures related to Gilead, AstraZeneca, AbbVie, Sunesis, Johnson & Johnson, TG Therapeutics, Loxo Oncology, DTRM Biopharma, Genentech, Janssen, Acerta Pharma, Pharmacyclics, and Celgene.

SOURCE: Mato AR et al. ASH 2019, Abstract 502.

ORLANDO – For a patient with chronic lymphocytic leukemia (CLL) who has discontinued venetoclax, choosing the best next therapy may depend on what novel agents the patient was exposed to and why they discontinued them, according to Anthony R. Mato, MD, with the Center for CLL at Memorial Sloan Kettering Cancer Center in New York.

Andrew D. Bowser/MDedge News

If the patient is Bruton tyrosine kinase (BTK) inhibitor naive, then use of a BTK inhibitor after venetoclax would be supported, Dr. Mato said, by the high overall response rates and durable remissions that he and his coinvestigators documented in a retrospective, multicenter study designed specifically to address the gap in knowledge regarding what to use after venetoclax.

If the patient is BTK inhibitor exposed, then the reason for discontinuation needs to be considered before going with that venetoclax-to-BTK inhibitor sequence, Dr. Mato said during an oral presentation at the annual meeting of the American Society of Hematology.

“In patients with resistance to a BTK inhibitor, the sequence was not supported – it did not appear to be effective,” he said. “However, in the setting of intolerance, an alternate BTK inhibitor could be considered.”

The study did not support a venetoclax-to-PI3K inhibitor sequence in PI3K-naive patients, he added, noting that remissions did not appear to be durable, suggesting a potential overlap in resistance mechanisms between agents.

All told, the most effective therapies for in the postvenetoclax setting included the use of a BTK inhibitor in BTK inhibitor–naive or previously responsive patients, and allogeneic transplant following double novel-agent exposure.

“These data may provide support for venetoclax’s earlier use in the course of CLL, and may guide clinical practice and aid in the design of future clinical trials to address sequencing of novel agents,” Dr. Mato told attendees.

While prospective and real-world data clearly show that venetoclax is active in ibrutinib- or idelalisib-exposed patients, data are conversely “variable and limited” with regard to outcomes for next therapies following venetoclax.

“Current data addressing this key sequencing question, I feel, is a major limitation in supporting the sequence of venetoclax to a BTK inhibitor,” Dr. Mato said.

Accordingly, Dr. Mato and colleagues at 31 centers internationally planned and conducted this study, which included data on 326 patients treated with venetoclax who then discontinued for any reason.

“I wanted to highlight that 50% of the sites for this trial were recruited by a single tweet,” said Dr. Mato, adding that he and his coauthors received no funding to conduct this study and volunteered their time to complete it.

They found that, in BTK inhibitor–naive patients who discontinued venetoclax, subsequent BTK inhibitor treatment was associated with a high overall response rate and durable remissions, with a median progression-free survival (PFS) of 32 months.

In BTK inhibitor–exposed patients, response to postvenetoclax BTK inhibitor treatment depended on the reason for discontinuation, with a favorable result (PFS not reached with a mean follow-up of 7.7 months) in patients who were intolerant of the prior BTK inhibitor. By contrast, median PFS was only about 4 months for patients who were resistant to the prior BTK inhibitor.

PI3K inhibitors did not produce durable remissions after venetoclax, with a median PFS also of just 4 months, Dr. Mato reported.

However, cellular therapies appeared to be effective after venetoclax. Allogeneic hematopoietic stem cell transplantation was particularly effective, with the median PFS not reached, while chimeric antigen receptor T-cell therapy produced a PFS of 9 months.

Dr. Mato emphasized that the results of the retrospective trial were “hypothesis generating” and noted that patients in the study had received a median of 3, and up to 11, prior therapies. “This population are probably not our patients receiving venetoclax in clinical practice. They’re more heavily pretreated.”

Dr. Mato reported disclosures related to Gilead, AstraZeneca, AbbVie, Sunesis, Johnson & Johnson, TG Therapeutics, Loxo Oncology, DTRM Biopharma, Genentech, Janssen, Acerta Pharma, Pharmacyclics, and Celgene.

SOURCE: Mato AR et al. ASH 2019, Abstract 502.

ORLANDO – For a patient with chronic lymphocytic leukemia (CLL) who has discontinued venetoclax, choosing the best next therapy may depend on what novel agents the patient was exposed to and why they discontinued them, according to Anthony R. Mato, MD, with the Center for CLL at Memorial Sloan Kettering Cancer Center in New York.

Andrew D. Bowser/MDedge News

If the patient is Bruton tyrosine kinase (BTK) inhibitor naive, then use of a BTK inhibitor after venetoclax would be supported, Dr. Mato said, by the high overall response rates and durable remissions that he and his coinvestigators documented in a retrospective, multicenter study designed specifically to address the gap in knowledge regarding what to use after venetoclax.

If the patient is BTK inhibitor exposed, then the reason for discontinuation needs to be considered before going with that venetoclax-to-BTK inhibitor sequence, Dr. Mato said during an oral presentation at the annual meeting of the American Society of Hematology.

“In patients with resistance to a BTK inhibitor, the sequence was not supported – it did not appear to be effective,” he said. “However, in the setting of intolerance, an alternate BTK inhibitor could be considered.”

The study did not support a venetoclax-to-PI3K inhibitor sequence in PI3K-naive patients, he added, noting that remissions did not appear to be durable, suggesting a potential overlap in resistance mechanisms between agents.

All told, the most effective therapies for in the postvenetoclax setting included the use of a BTK inhibitor in BTK inhibitor–naive or previously responsive patients, and allogeneic transplant following double novel-agent exposure.

“These data may provide support for venetoclax’s earlier use in the course of CLL, and may guide clinical practice and aid in the design of future clinical trials to address sequencing of novel agents,” Dr. Mato told attendees.

While prospective and real-world data clearly show that venetoclax is active in ibrutinib- or idelalisib-exposed patients, data are conversely “variable and limited” with regard to outcomes for next therapies following venetoclax.

“Current data addressing this key sequencing question, I feel, is a major limitation in supporting the sequence of venetoclax to a BTK inhibitor,” Dr. Mato said.

Accordingly, Dr. Mato and colleagues at 31 centers internationally planned and conducted this study, which included data on 326 patients treated with venetoclax who then discontinued for any reason.

“I wanted to highlight that 50% of the sites for this trial were recruited by a single tweet,” said Dr. Mato, adding that he and his coauthors received no funding to conduct this study and volunteered their time to complete it.

They found that, in BTK inhibitor–naive patients who discontinued venetoclax, subsequent BTK inhibitor treatment was associated with a high overall response rate and durable remissions, with a median progression-free survival (PFS) of 32 months.

In BTK inhibitor–exposed patients, response to postvenetoclax BTK inhibitor treatment depended on the reason for discontinuation, with a favorable result (PFS not reached with a mean follow-up of 7.7 months) in patients who were intolerant of the prior BTK inhibitor. By contrast, median PFS was only about 4 months for patients who were resistant to the prior BTK inhibitor.

PI3K inhibitors did not produce durable remissions after venetoclax, with a median PFS also of just 4 months, Dr. Mato reported.

However, cellular therapies appeared to be effective after venetoclax. Allogeneic hematopoietic stem cell transplantation was particularly effective, with the median PFS not reached, while chimeric antigen receptor T-cell therapy produced a PFS of 9 months.

Dr. Mato emphasized that the results of the retrospective trial were “hypothesis generating” and noted that patients in the study had received a median of 3, and up to 11, prior therapies. “This population are probably not our patients receiving venetoclax in clinical practice. They’re more heavily pretreated.”

Dr. Mato reported disclosures related to Gilead, AstraZeneca, AbbVie, Sunesis, Johnson & Johnson, TG Therapeutics, Loxo Oncology, DTRM Biopharma, Genentech, Janssen, Acerta Pharma, Pharmacyclics, and Celgene.

SOURCE: Mato AR et al. ASH 2019, Abstract 502.

ORLANDO – There is an urgent need for new therapies to treat relapsed or refractory peripheral T-cell lymphoma, but results of a phase 2 study suggest that monotherapy with the immune checkpoint inhibitor nivolumab (Opdivo) is not the hoped-for salvage treatment.

Neil Osterweil/MDedge News

An interim analysis of data on 12 patients with peripheral T-cell lymphoma (PTCL) treated with nivolumab monotherapy showed an overall response rate of 33%, consisting of 2 complete responses and 2 partial responses. But the responses were short lived, and one patient had hyperprogressive disease – dramatic progression within one cycle of treatment – while two more had progression within two cycles, leading to a trial halt, reported N. Nora Bennani, MD, from the Mayo Clinic in Rochester, Minn.

“These findings likely reflect the distinct biology of PTCL and should be considered when designing future studies using checkpoint inhibitors in these diseases,” she said at the annual meeting of the American Society of Hematology.

The rationale for using an immune checkpoint inhibitor directed against the programmed death–1 protein and its ligands (PD and PD-L1/2) is that malignant cells in PTCL induce a profoundly immunosuppressive tumor microenvironment. Checkpoint inhibitors have shown strong activity against relapsed Hodgkin lymphoma, and the Mayo Clinic researchers speculated that an anti-PD-1 agent could have a similar effect in PTCL.

They had originally planned to enroll 29 patients into a phase 2 trial with nivolumab delivered 240 mg every 2 weeks for eight cycles, followed by a dose of 480 mg given every 4 weeks until disease progression or intolerable toxicities.

Patients were eligible if they had biopsy-confirmed relapsed or refractory PTCL, measurable disease on cross-sectional imaging of at least 1.5 cm, and prior systemic chemoimmunotherapy and/or autologous stem cell transplantation.

The interim analysis included 12 patients who received at least one dose of nivolumab. Of the 12 patients, 6 had angioimmunoblastic T-cell lymphoma (AITL), 3 had PTCL not otherwise specified, and 1 each had ALK-negative anaplastic large cell lymphoma (ALK-ALCL), enteropathy-associated T-cell lymphoma (EATL), or hepatosplenic gamma/delta T-cell lymphoma.

All patients had Ann Arbor stage III/IV disease, and 11 had extranodal involvement.

As noted, there were 4 responses among the 12 patients, consisting of 1 complete response in the patient with ALK-ALCL and 1 in a patient with AITL, and 2 partial responses – 1 in a patient with PTCL-NOS, and 1 in the patient with EATL.

The median progression-free survival for all 12 patients was short at 2.7 months, and the median overall survival was estimated at 6.7 months.

“It was staggering to see this: The duration of response was significantly short, less than 2 months,” Dr. Bennani said.

Nonhematologic toxicities were seen in 5 of the 12 patients (42%), and hematologic adverse events occurred in 3 (25%). All patients are now off treatment, 10 because of disease progression, 1 because of acute pancreatitis, and the aforementioned patient with hyperprogressive disease.

The patient with hyperprogressive disease had significant progression in tonsillar and cervical lymphadenopathy within 7-10 days of nivolumab infusion, with biopsy-proven AITL in the involved nodes.

“I believe that, in this patient population, combination therapies will be key. I think checkpoint blockers alone are not going to be sufficient to see meaningful outcomes in these patients,” Dr. Bennani said in an interview.

“An overall response rate of 33% is significant, because most other agents that were FDA approved in this patient population have response rates around 30%,” she said, adding that it’s possible that the patients with rapid progression had disease too advanced to be effectively treated with a checkpoint inhibitor.

“Ideally however, if we want to move forward, it will need to be with combinations of checkpoint inhibitors with HDAC [histone deacetylase] inhibitors, hypomethylating agents, or even PI3 kinase inhibitors,” she said.

­The study was supported by Bristol-Myers Squibb. Dr. Bennani reported research funding and advisory board activities for Bristol-Myers Squibb and others.

SOURCE: Bennani NN et al. ASH 2019, Abstract 467.

ORLANDO – There is an urgent need for new therapies to treat relapsed or refractory peripheral T-cell lymphoma, but results of a phase 2 study suggest that monotherapy with the immune checkpoint inhibitor nivolumab (Opdivo) is not the hoped-for salvage treatment.

Neil Osterweil/MDedge News

An interim analysis of data on 12 patients with peripheral T-cell lymphoma (PTCL) treated with nivolumab monotherapy showed an overall response rate of 33%, consisting of 2 complete responses and 2 partial responses. But the responses were short lived, and one patient had hyperprogressive disease – dramatic progression within one cycle of treatment – while two more had progression within two cycles, leading to a trial halt, reported N. Nora Bennani, MD, from the Mayo Clinic in Rochester, Minn.

“These findings likely reflect the distinct biology of PTCL and should be considered when designing future studies using checkpoint inhibitors in these diseases,” she said at the annual meeting of the American Society of Hematology.

The rationale for using an immune checkpoint inhibitor directed against the programmed death–1 protein and its ligands (PD and PD-L1/2) is that malignant cells in PTCL induce a profoundly immunosuppressive tumor microenvironment. Checkpoint inhibitors have shown strong activity against relapsed Hodgkin lymphoma, and the Mayo Clinic researchers speculated that an anti-PD-1 agent could have a similar effect in PTCL.

They had originally planned to enroll 29 patients into a phase 2 trial with nivolumab delivered 240 mg every 2 weeks for eight cycles, followed by a dose of 480 mg given every 4 weeks until disease progression or intolerable toxicities.

Patients were eligible if they had biopsy-confirmed relapsed or refractory PTCL, measurable disease on cross-sectional imaging of at least 1.5 cm, and prior systemic chemoimmunotherapy and/or autologous stem cell transplantation.

The interim analysis included 12 patients who received at least one dose of nivolumab. Of the 12 patients, 6 had angioimmunoblastic T-cell lymphoma (AITL), 3 had PTCL not otherwise specified, and 1 each had ALK-negative anaplastic large cell lymphoma (ALK-ALCL), enteropathy-associated T-cell lymphoma (EATL), or hepatosplenic gamma/delta T-cell lymphoma.

All patients had Ann Arbor stage III/IV disease, and 11 had extranodal involvement.

As noted, there were 4 responses among the 12 patients, consisting of 1 complete response in the patient with ALK-ALCL and 1 in a patient with AITL, and 2 partial responses – 1 in a patient with PTCL-NOS, and 1 in the patient with EATL.

The median progression-free survival for all 12 patients was short at 2.7 months, and the median overall survival was estimated at 6.7 months.

“It was staggering to see this: The duration of response was significantly short, less than 2 months,” Dr. Bennani said.

Nonhematologic toxicities were seen in 5 of the 12 patients (42%), and hematologic adverse events occurred in 3 (25%). All patients are now off treatment, 10 because of disease progression, 1 because of acute pancreatitis, and the aforementioned patient with hyperprogressive disease.

The patient with hyperprogressive disease had significant progression in tonsillar and cervical lymphadenopathy within 7-10 days of nivolumab infusion, with biopsy-proven AITL in the involved nodes.

“I believe that, in this patient population, combination therapies will be key. I think checkpoint blockers alone are not going to be sufficient to see meaningful outcomes in these patients,” Dr. Bennani said in an interview.

“An overall response rate of 33% is significant, because most other agents that were FDA approved in this patient population have response rates around 30%,” she said, adding that it’s possible that the patients with rapid progression had disease too advanced to be effectively treated with a checkpoint inhibitor.

“Ideally however, if we want to move forward, it will need to be with combinations of checkpoint inhibitors with HDAC [histone deacetylase] inhibitors, hypomethylating agents, or even PI3 kinase inhibitors,” she said.

­The study was supported by Bristol-Myers Squibb. Dr. Bennani reported research funding and advisory board activities for Bristol-Myers Squibb and others.

SOURCE: Bennani NN et al. ASH 2019, Abstract 467.

ORLANDO – There is an urgent need for new therapies to treat relapsed or refractory peripheral T-cell lymphoma, but results of a phase 2 study suggest that monotherapy with the immune checkpoint inhibitor nivolumab (Opdivo) is not the hoped-for salvage treatment.

Neil Osterweil/MDedge News

An interim analysis of data on 12 patients with peripheral T-cell lymphoma (PTCL) treated with nivolumab monotherapy showed an overall response rate of 33%, consisting of 2 complete responses and 2 partial responses. But the responses were short lived, and one patient had hyperprogressive disease – dramatic progression within one cycle of treatment – while two more had progression within two cycles, leading to a trial halt, reported N. Nora Bennani, MD, from the Mayo Clinic in Rochester, Minn.

“These findings likely reflect the distinct biology of PTCL and should be considered when designing future studies using checkpoint inhibitors in these diseases,” she said at the annual meeting of the American Society of Hematology.

The rationale for using an immune checkpoint inhibitor directed against the programmed death–1 protein and its ligands (PD and PD-L1/2) is that malignant cells in PTCL induce a profoundly immunosuppressive tumor microenvironment. Checkpoint inhibitors have shown strong activity against relapsed Hodgkin lymphoma, and the Mayo Clinic researchers speculated that an anti-PD-1 agent could have a similar effect in PTCL.

They had originally planned to enroll 29 patients into a phase 2 trial with nivolumab delivered 240 mg every 2 weeks for eight cycles, followed by a dose of 480 mg given every 4 weeks until disease progression or intolerable toxicities.

Patients were eligible if they had biopsy-confirmed relapsed or refractory PTCL, measurable disease on cross-sectional imaging of at least 1.5 cm, and prior systemic chemoimmunotherapy and/or autologous stem cell transplantation.

The interim analysis included 12 patients who received at least one dose of nivolumab. Of the 12 patients, 6 had angioimmunoblastic T-cell lymphoma (AITL), 3 had PTCL not otherwise specified, and 1 each had ALK-negative anaplastic large cell lymphoma (ALK-ALCL), enteropathy-associated T-cell lymphoma (EATL), or hepatosplenic gamma/delta T-cell lymphoma.

All patients had Ann Arbor stage III/IV disease, and 11 had extranodal involvement.

As noted, there were 4 responses among the 12 patients, consisting of 1 complete response in the patient with ALK-ALCL and 1 in a patient with AITL, and 2 partial responses – 1 in a patient with PTCL-NOS, and 1 in the patient with EATL.

The median progression-free survival for all 12 patients was short at 2.7 months, and the median overall survival was estimated at 6.7 months.

“It was staggering to see this: The duration of response was significantly short, less than 2 months,” Dr. Bennani said.

Nonhematologic toxicities were seen in 5 of the 12 patients (42%), and hematologic adverse events occurred in 3 (25%). All patients are now off treatment, 10 because of disease progression, 1 because of acute pancreatitis, and the aforementioned patient with hyperprogressive disease.

The patient with hyperprogressive disease had significant progression in tonsillar and cervical lymphadenopathy within 7-10 days of nivolumab infusion, with biopsy-proven AITL in the involved nodes.

“I believe that, in this patient population, combination therapies will be key. I think checkpoint blockers alone are not going to be sufficient to see meaningful outcomes in these patients,” Dr. Bennani said in an interview.

“An overall response rate of 33% is significant, because most other agents that were FDA approved in this patient population have response rates around 30%,” she said, adding that it’s possible that the patients with rapid progression had disease too advanced to be effectively treated with a checkpoint inhibitor.

“Ideally however, if we want to move forward, it will need to be with combinations of checkpoint inhibitors with HDAC [histone deacetylase] inhibitors, hypomethylating agents, or even PI3 kinase inhibitors,” she said.

­The study was supported by Bristol-Myers Squibb. Dr. Bennani reported research funding and advisory board activities for Bristol-Myers Squibb and others.

SOURCE: Bennani NN et al. ASH 2019, Abstract 467.

ORLANDO – Patients with diffuse large B-cell lymphoma (DLBCL) who are members of an ethnic or racial minority do not have worse outcomes than whites when they receive appropriate treatment and institutional support, a study on disparities in cancer care shows.

Neil Osterweil/MDedge News

Although previous studies have shown that minorities with DLBCL have worse outcomes than do whites, results of a study comparing outcomes from 155 patients of white heritage with those of 41 patients from black, Hispanic, or other minority backgrounds found no significant differences in either progression-free survival (PFS) or overall survival in 2 years over follow-up, reported Nilanjan Ghosh, MD, PhD, from the Levine Cancer Institute, Atrium Health, in Charlotte, N.C.

He attributes the results to his center’s robust nurse navigation program, equal access among all patients – regardless of ability to pay – to standard treatments, and to the availability of clinical trial participation and stem cell transplantation.

“I think a key message is that if you are able to offer the same treatment and clinical trials to people irrespective of their race or socioeconomic status and can provide support, you can get equal outcomes as long as the biology is the same in both groups,” he said at a briefing prior to presentation of data in an oral abstract session at the annual meeting of the American Society of Hematology.

Dr. Ghosh pointed to four separate studies that showed that minority populations with DLBCL have worse outcomes than did whites, and noted that both uninsured and Medicaid-insured patients have also been shown to have poorer results, suggesting a role of socioeconomic factors in determining who gets optimum care and who does not.

The investigators compared PFS and OS among white and nonwhite patients with DLBCL treated in their institution, which has a safety-net cancer center. They also looked at the frequencies of clinical trial participation and stem cell transplantation between the groups.

The study included all patients with de novo DLBCL who presented to their center during January 2016–January 2019. They used patient-reported descriptors of race/ethnicity to create one of two cohorts: either self-identified whites (155 patients) or nonwhites (41), a group that included black patients, Hispanic patients, Asian Americans, and Native Americans.

The authors collected data on demographics, disease characteristics (including revised International Prognostic Index and double-hit status), insurance data, treatment, trial enrollment, progression, and death.

They found that nonwhites were significantly younger at diagnosis (median 56 vs. 64 years; P = .007), with an even distribution between the sexes in each group.

Two-thirds of both white and nonwhite patients had government insurance (Medicare or Medicaid). Of the remaining patients, 33% of white had private insurance, compared with 27% of nonwhites. No whites were uninsured, but 3 of the 41 nonwhites (7%) had no insurance.

Of the 155 white patients, 121 (86%) received nurse navigation services, as did 33 of 41 (81%) of nonwhites. The services include lodging assistance for homeless patients, transportation services for patients without cars, and care coordination among primary care physicians, oncologists, and other specialists. The services are part of the center’s standard practice, with excess costs, if any, folded into the budget, Dr. Ghosh said.

Looking at disease characteristics and treatment, the investigators found that risk profiles were similar between the groups. A higher percentage of whites had double-hit lymphoma (11% vs. 7%), but this difference was not statistically significant.

The investigators also found that in their program race was not a barrier to optimum therapy, with 96% of whites and 98% of nonwhites receiving frontline therapy with an anthracycline and rituximab-based regimen, and 4% and 2%, respectively received a non–anthracycline based regimen.

In each group, 39% of patients had disease that either relapsed or was refractory to frontline therapy.

In all, 11% of whites and 12% of nonwhites enrolled in clinical trials, 11% and 19%, respectively, underwent stem cell transplantation.

For patients with relapsed/refractory disease, the 2-year PFS rates were 60% for whites, and 63% for nonwhites, and the 2-year OS rates were 74% and 81%, respectively.

Dr. Ghosh and colleagues concluded that “our safety net cancer center, with extensive nurse navigator support and access to standard treatments, stem cell transplants, and cutting-edge clinical trials may abrogate the inferior outcomes in minority populations that have been previously reported.”

The study was internally funded. Dr. Ghosh reported consulting fees, research funding, speakers bureau activity, and/or honoraria from multiple companies.

SOURCE: Hu B et al. ASH 2019. Abstract 425.

ORLANDO – Patients with diffuse large B-cell lymphoma (DLBCL) who are members of an ethnic or racial minority do not have worse outcomes than whites when they receive appropriate treatment and institutional support, a study on disparities in cancer care shows.

Neil Osterweil/MDedge News

Although previous studies have shown that minorities with DLBCL have worse outcomes than do whites, results of a study comparing outcomes from 155 patients of white heritage with those of 41 patients from black, Hispanic, or other minority backgrounds found no significant differences in either progression-free survival (PFS) or overall survival in 2 years over follow-up, reported Nilanjan Ghosh, MD, PhD, from the Levine Cancer Institute, Atrium Health, in Charlotte, N.C.

He attributes the results to his center’s robust nurse navigation program, equal access among all patients – regardless of ability to pay – to standard treatments, and to the availability of clinical trial participation and stem cell transplantation.

“I think a key message is that if you are able to offer the same treatment and clinical trials to people irrespective of their race or socioeconomic status and can provide support, you can get equal outcomes as long as the biology is the same in both groups,” he said at a briefing prior to presentation of data in an oral abstract session at the annual meeting of the American Society of Hematology.

Dr. Ghosh pointed to four separate studies that showed that minority populations with DLBCL have worse outcomes than did whites, and noted that both uninsured and Medicaid-insured patients have also been shown to have poorer results, suggesting a role of socioeconomic factors in determining who gets optimum care and who does not.

The investigators compared PFS and OS among white and nonwhite patients with DLBCL treated in their institution, which has a safety-net cancer center. They also looked at the frequencies of clinical trial participation and stem cell transplantation between the groups.

The study included all patients with de novo DLBCL who presented to their center during January 2016–January 2019. They used patient-reported descriptors of race/ethnicity to create one of two cohorts: either self-identified whites (155 patients) or nonwhites (41), a group that included black patients, Hispanic patients, Asian Americans, and Native Americans.

The authors collected data on demographics, disease characteristics (including revised International Prognostic Index and double-hit status), insurance data, treatment, trial enrollment, progression, and death.

They found that nonwhites were significantly younger at diagnosis (median 56 vs. 64 years; P = .007), with an even distribution between the sexes in each group.

Two-thirds of both white and nonwhite patients had government insurance (Medicare or Medicaid). Of the remaining patients, 33% of white had private insurance, compared with 27% of nonwhites. No whites were uninsured, but 3 of the 41 nonwhites (7%) had no insurance.

Of the 155 white patients, 121 (86%) received nurse navigation services, as did 33 of 41 (81%) of nonwhites. The services include lodging assistance for homeless patients, transportation services for patients without cars, and care coordination among primary care physicians, oncologists, and other specialists. The services are part of the center’s standard practice, with excess costs, if any, folded into the budget, Dr. Ghosh said.

Looking at disease characteristics and treatment, the investigators found that risk profiles were similar between the groups. A higher percentage of whites had double-hit lymphoma (11% vs. 7%), but this difference was not statistically significant.

The investigators also found that in their program race was not a barrier to optimum therapy, with 96% of whites and 98% of nonwhites receiving frontline therapy with an anthracycline and rituximab-based regimen, and 4% and 2%, respectively received a non–anthracycline based regimen.

In each group, 39% of patients had disease that either relapsed or was refractory to frontline therapy.

In all, 11% of whites and 12% of nonwhites enrolled in clinical trials, 11% and 19%, respectively, underwent stem cell transplantation.

For patients with relapsed/refractory disease, the 2-year PFS rates were 60% for whites, and 63% for nonwhites, and the 2-year OS rates were 74% and 81%, respectively.

Dr. Ghosh and colleagues concluded that “our safety net cancer center, with extensive nurse navigator support and access to standard treatments, stem cell transplants, and cutting-edge clinical trials may abrogate the inferior outcomes in minority populations that have been previously reported.”

The study was internally funded. Dr. Ghosh reported consulting fees, research funding, speakers bureau activity, and/or honoraria from multiple companies.

SOURCE: Hu B et al. ASH 2019. Abstract 425.

ORLANDO – Patients with diffuse large B-cell lymphoma (DLBCL) who are members of an ethnic or racial minority do not have worse outcomes than whites when they receive appropriate treatment and institutional support, a study on disparities in cancer care shows.

Neil Osterweil/MDedge News

Although previous studies have shown that minorities with DLBCL have worse outcomes than do whites, results of a study comparing outcomes from 155 patients of white heritage with those of 41 patients from black, Hispanic, or other minority backgrounds found no significant differences in either progression-free survival (PFS) or overall survival in 2 years over follow-up, reported Nilanjan Ghosh, MD, PhD, from the Levine Cancer Institute, Atrium Health, in Charlotte, N.C.

He attributes the results to his center’s robust nurse navigation program, equal access among all patients – regardless of ability to pay – to standard treatments, and to the availability of clinical trial participation and stem cell transplantation.

“I think a key message is that if you are able to offer the same treatment and clinical trials to people irrespective of their race or socioeconomic status and can provide support, you can get equal outcomes as long as the biology is the same in both groups,” he said at a briefing prior to presentation of data in an oral abstract session at the annual meeting of the American Society of Hematology.

Dr. Ghosh pointed to four separate studies that showed that minority populations with DLBCL have worse outcomes than did whites, and noted that both uninsured and Medicaid-insured patients have also been shown to have poorer results, suggesting a role of socioeconomic factors in determining who gets optimum care and who does not.

The investigators compared PFS and OS among white and nonwhite patients with DLBCL treated in their institution, which has a safety-net cancer center. They also looked at the frequencies of clinical trial participation and stem cell transplantation between the groups.

The study included all patients with de novo DLBCL who presented to their center during January 2016–January 2019. They used patient-reported descriptors of race/ethnicity to create one of two cohorts: either self-identified whites (155 patients) or nonwhites (41), a group that included black patients, Hispanic patients, Asian Americans, and Native Americans.

The authors collected data on demographics, disease characteristics (including revised International Prognostic Index and double-hit status), insurance data, treatment, trial enrollment, progression, and death.

They found that nonwhites were significantly younger at diagnosis (median 56 vs. 64 years; P = .007), with an even distribution between the sexes in each group.

Two-thirds of both white and nonwhite patients had government insurance (Medicare or Medicaid). Of the remaining patients, 33% of white had private insurance, compared with 27% of nonwhites. No whites were uninsured, but 3 of the 41 nonwhites (7%) had no insurance.

Of the 155 white patients, 121 (86%) received nurse navigation services, as did 33 of 41 (81%) of nonwhites. The services include lodging assistance for homeless patients, transportation services for patients without cars, and care coordination among primary care physicians, oncologists, and other specialists. The services are part of the center’s standard practice, with excess costs, if any, folded into the budget, Dr. Ghosh said.

Looking at disease characteristics and treatment, the investigators found that risk profiles were similar between the groups. A higher percentage of whites had double-hit lymphoma (11% vs. 7%), but this difference was not statistically significant.

The investigators also found that in their program race was not a barrier to optimum therapy, with 96% of whites and 98% of nonwhites receiving frontline therapy with an anthracycline and rituximab-based regimen, and 4% and 2%, respectively received a non–anthracycline based regimen.

In each group, 39% of patients had disease that either relapsed or was refractory to frontline therapy.

In all, 11% of whites and 12% of nonwhites enrolled in clinical trials, 11% and 19%, respectively, underwent stem cell transplantation.

For patients with relapsed/refractory disease, the 2-year PFS rates were 60% for whites, and 63% for nonwhites, and the 2-year OS rates were 74% and 81%, respectively.

Dr. Ghosh and colleagues concluded that “our safety net cancer center, with extensive nurse navigator support and access to standard treatments, stem cell transplants, and cutting-edge clinical trials may abrogate the inferior outcomes in minority populations that have been previously reported.”

The study was internally funded. Dr. Ghosh reported consulting fees, research funding, speakers bureau activity, and/or honoraria from multiple companies.

SOURCE: Hu B et al. ASH 2019. Abstract 425.

ORLANDO – Combining aspirin and direct oral anticoagulant (DOAC) therapy for the secondary prevention of venous thromboembolism (VTE) or the prevention of stroke associated with nonvalvular atrial fibrillation (NVAF) without a clear indication was associated with increased bleeding risks in a large registry-based cohort.

Sharon Worcester/MDedge News

The study, which involved a cohort of 2,045 patients who were followed at 6 anticoagulation clinics in Michigan during January 2009–June 2019, also found no apparent improvement in thrombosis incidence with the addition of aspirin, Jordan K. Schaefer, MD, reported during a press briefing at the annual meeting of the American Society of Hematology.

Of the cohort patients, 639 adults who received a DOAC plus aspirin after VTE or for NVAF without a clear indication were compared with 639 propensity-matched controls. The bleeding event rate per 100 patient years was 39.50 vs. 32.32 at an average of 15.2 months of follow-up in the combination therapy and DOAC monotherapy groups, respectively, said Dr. Schaefer of the division of hematology/oncology, department of internal medicine, University of Michigan, Ann Arbor.

“This result was statistically significant for clinically relevant non-major bleeding, with an 18.7 rate per 100 patient years, compared with 13.5 for DOAC monotherapy,” (P = .02), he said. “We also saw a significant increase in non-major bleeding with combination therapy, compared with direct oral anticoagulant monotherapy” (rate, 32.82 vs. 25.88; P =.04).

No significant difference was seen overall (P =.07) or for other specific types of bleeding, he noted.

The observed rates of thrombosis in the groups, respectively, were 2.35 and 2.23 per 100 patient years (P =.95), he said, noting that patients on combination therapy also had more emergency department visits and hospitalizations, but those differences were not statistically significant.

“Direct-acting oral anticoagulants, which include apixaban, dabigatran, edoxaban, and rivaroxaban, are increasingly used in clinical practice for indications that include the prevention of strokes for patients with nonvalvular atrial fibrillation, and the treatment and secondary prevention of venous thromboembolic disease,” Dr. Schaefer said.

Aspirin is commonly used in clinical practice for various indications, including primary prevention of heart attacks, strokes, and colorectal cancer, as well as for thromboprophylaxis in patients with certain blood disorders or with certain cardiac devices, he added.

“Aspirin is used for the secondary prevention of thrombosis for patients with known coronary artery disease, peripheral artery disease, or carotid artery disease,” he said. “And while adding aspirin to a DOAC is often appropriate after acute coronary syndromes or percutaneous coronary intervention, many patients receive the combination therapy without a clear indication, he said, noting that increasing evidence in recent years, largely from patients treated with warfarin and aspirin, suggest that the approach may do more harm than good for certain patients.

Specifically, there’s a question of whether aspirin is increasing the rates of bleeding without protecting patients from adverse thrombotic outcomes.

“This has specifically been a concern for patients who are on full-dose anticoagulation,” he said.

In the current study, patient demographics, comorbidities, and concurrent medications were well balanced in the treatment and control groups after propensity score matching, he said, noting that patients with a history of heart valve replacement, recent MI, or less than 3 months of follow-up were excluded.

“These findings need to be confirmed in larger studies, but until such data [are] available, clinicians and patients should continue to balance the relative risks and benefits of adding aspirin to their direct oral anticoagulant therapy,” Dr. Schaefer said. “Further research needs to evaluate key subgroups to see if any particular population may benefit from combination therapy compared to DOAC therapy alone.”

Dr. Schaefer reported having no disclosures.

[email protected]

SOURCE: Schaeffer J et al. ASH 2019. Abstract 787.

ORLANDO – Combining aspirin and direct oral anticoagulant (DOAC) therapy for the secondary prevention of venous thromboembolism (VTE) or the prevention of stroke associated with nonvalvular atrial fibrillation (NVAF) without a clear indication was associated with increased bleeding risks in a large registry-based cohort.

Sharon Worcester/MDedge News

The study, which involved a cohort of 2,045 patients who were followed at 6 anticoagulation clinics in Michigan during January 2009–June 2019, also found no apparent improvement in thrombosis incidence with the addition of aspirin, Jordan K. Schaefer, MD, reported during a press briefing at the annual meeting of the American Society of Hematology.

Of the cohort patients, 639 adults who received a DOAC plus aspirin after VTE or for NVAF without a clear indication were compared with 639 propensity-matched controls. The bleeding event rate per 100 patient years was 39.50 vs. 32.32 at an average of 15.2 months of follow-up in the combination therapy and DOAC monotherapy groups, respectively, said Dr. Schaefer of the division of hematology/oncology, department of internal medicine, University of Michigan, Ann Arbor.

“This result was statistically significant for clinically relevant non-major bleeding, with an 18.7 rate per 100 patient years, compared with 13.5 for DOAC monotherapy,” (P = .02), he said. “We also saw a significant increase in non-major bleeding with combination therapy, compared with direct oral anticoagulant monotherapy” (rate, 32.82 vs. 25.88; P =.04).

No significant difference was seen overall (P =.07) or for other specific types of bleeding, he noted.

The observed rates of thrombosis in the groups, respectively, were 2.35 and 2.23 per 100 patient years (P =.95), he said, noting that patients on combination therapy also had more emergency department visits and hospitalizations, but those differences were not statistically significant.

“Direct-acting oral anticoagulants, which include apixaban, dabigatran, edoxaban, and rivaroxaban, are increasingly used in clinical practice for indications that include the prevention of strokes for patients with nonvalvular atrial fibrillation, and the treatment and secondary prevention of venous thromboembolic disease,” Dr. Schaefer said.

Aspirin is commonly used in clinical practice for various indications, including primary prevention of heart attacks, strokes, and colorectal cancer, as well as for thromboprophylaxis in patients with certain blood disorders or with certain cardiac devices, he added.

“Aspirin is used for the secondary prevention of thrombosis for patients with known coronary artery disease, peripheral artery disease, or carotid artery disease,” he said. “And while adding aspirin to a DOAC is often appropriate after acute coronary syndromes or percutaneous coronary intervention, many patients receive the combination therapy without a clear indication, he said, noting that increasing evidence in recent years, largely from patients treated with warfarin and aspirin, suggest that the approach may do more harm than good for certain patients.

Specifically, there’s a question of whether aspirin is increasing the rates of bleeding without protecting patients from adverse thrombotic outcomes.

“This has specifically been a concern for patients who are on full-dose anticoagulation,” he said.

In the current study, patient demographics, comorbidities, and concurrent medications were well balanced in the treatment and control groups after propensity score matching, he said, noting that patients with a history of heart valve replacement, recent MI, or less than 3 months of follow-up were excluded.

“These findings need to be confirmed in larger studies, but until such data [are] available, clinicians and patients should continue to balance the relative risks and benefits of adding aspirin to their direct oral anticoagulant therapy,” Dr. Schaefer said. “Further research needs to evaluate key subgroups to see if any particular population may benefit from combination therapy compared to DOAC therapy alone.”

Dr. Schaefer reported having no disclosures.

[email protected]

SOURCE: Schaeffer J et al. ASH 2019. Abstract 787.

ORLANDO – Combining aspirin and direct oral anticoagulant (DOAC) therapy for the secondary prevention of venous thromboembolism (VTE) or the prevention of stroke associated with nonvalvular atrial fibrillation (NVAF) without a clear indication was associated with increased bleeding risks in a large registry-based cohort.

Sharon Worcester/MDedge News

The study, which involved a cohort of 2,045 patients who were followed at 6 anticoagulation clinics in Michigan during January 2009–June 2019, also found no apparent improvement in thrombosis incidence with the addition of aspirin, Jordan K. Schaefer, MD, reported during a press briefing at the annual meeting of the American Society of Hematology.

Of the cohort patients, 639 adults who received a DOAC plus aspirin after VTE or for NVAF without a clear indication were compared with 639 propensity-matched controls. The bleeding event rate per 100 patient years was 39.50 vs. 32.32 at an average of 15.2 months of follow-up in the combination therapy and DOAC monotherapy groups, respectively, said Dr. Schaefer of the division of hematology/oncology, department of internal medicine, University of Michigan, Ann Arbor.

“This result was statistically significant for clinically relevant non-major bleeding, with an 18.7 rate per 100 patient years, compared with 13.5 for DOAC monotherapy,” (P = .02), he said. “We also saw a significant increase in non-major bleeding with combination therapy, compared with direct oral anticoagulant monotherapy” (rate, 32.82 vs. 25.88; P =.04).

No significant difference was seen overall (P =.07) or for other specific types of bleeding, he noted.

The observed rates of thrombosis in the groups, respectively, were 2.35 and 2.23 per 100 patient years (P =.95), he said, noting that patients on combination therapy also had more emergency department visits and hospitalizations, but those differences were not statistically significant.

“Direct-acting oral anticoagulants, which include apixaban, dabigatran, edoxaban, and rivaroxaban, are increasingly used in clinical practice for indications that include the prevention of strokes for patients with nonvalvular atrial fibrillation, and the treatment and secondary prevention of venous thromboembolic disease,” Dr. Schaefer said.

Aspirin is commonly used in clinical practice for various indications, including primary prevention of heart attacks, strokes, and colorectal cancer, as well as for thromboprophylaxis in patients with certain blood disorders or with certain cardiac devices, he added.

“Aspirin is used for the secondary prevention of thrombosis for patients with known coronary artery disease, peripheral artery disease, or carotid artery disease,” he said. “And while adding aspirin to a DOAC is often appropriate after acute coronary syndromes or percutaneous coronary intervention, many patients receive the combination therapy without a clear indication, he said, noting that increasing evidence in recent years, largely from patients treated with warfarin and aspirin, suggest that the approach may do more harm than good for certain patients.

Specifically, there’s a question of whether aspirin is increasing the rates of bleeding without protecting patients from adverse thrombotic outcomes.

“This has specifically been a concern for patients who are on full-dose anticoagulation,” he said.

In the current study, patient demographics, comorbidities, and concurrent medications were well balanced in the treatment and control groups after propensity score matching, he said, noting that patients with a history of heart valve replacement, recent MI, or less than 3 months of follow-up were excluded.

“These findings need to be confirmed in larger studies, but until such data [are] available, clinicians and patients should continue to balance the relative risks and benefits of adding aspirin to their direct oral anticoagulant therapy,” Dr. Schaefer said. “Further research needs to evaluate key subgroups to see if any particular population may benefit from combination therapy compared to DOAC therapy alone.”

Dr. Schaefer reported having no disclosures.

[email protected]

SOURCE: Schaeffer J et al. ASH 2019. Abstract 787.