Breast Cancer

SAN ANTONIO – Programmed death-ligand 1 (PD-L1) expression on tumor-infiltrating immune cells is the best predictor of response to atezolizumab + nab-paclitaxel in patients with untreated metastatic triple-negative breast cancer, according to exploratory efficacy analyses of data from the phase 3 IMpassion130 trial.

The analyses of data for the 902 patients randomized to receive the PD-L1 inhibitor atezolizumab (Tecentriq) plus nanoparticle albumin-bound (nab)–paclitaxel or placebo plus nab-palcitaxel for the study also showed consistency between local and central estrogen-receptor, progesterone-receptor, and human epidermal growth factor–receptor 2 testing, Leisha A. Emens, MD, reported at the San Antonio Breast Cancer Symposium.

“IMpassion130 is the first phase 3 study to demonstrate a benefit from [atezolizumab + nab-paclitaxel] in metastatic triple-negative breast cancer (mTNBC),” said Dr. Emens, professor of medicine in hematology/oncology, coleader of the Hillman Cancer Immunology and Immunotherapy Program, and director of translational immunotherapy for the Women’s Cancer Research Center at the University of Pittsburgh Medical Center.

She explained that progression-free survival (PFS) was significantly better in PD-L1–positive mTNBC patients treated with the atezolizumab + nab-paclitaxel, than in those who received placebo + nab-paclitaxel (hazard ratios in the intent-to-treat population, 0.8 and 0.62, respectively).

At the first interim overall survival analysis, a clinically meaningful improvement in OS was seen in PD-L1–positive patients in the treatment group (HR, 0.62; median OS improvement from 15.5 months with placebo to 25 months), she added.

In exploratory analyses, Dr. Emens and her colleagues sought to evaluate whether preexisting immune biology is associated with clinical benefit from atezolizumab + nab-paclitaxel, as has been demonstrated in studies of other agents that target the PD-1 pathway in other cancer types of cancer. They also assessed BRCA 1/2 mutation status as a biomarker for response.

“In patients enrolled on the IMpassion130 trial we found that PD-L1 in triple-negative breast cancer was expressed primarily on tumor-infiltrating immune cells,” she said. “In contrast to this, we found a very low rate of PD-L1 expression specifically on tumor cells across the patient population.”

Looking at both of those biomarkers together showed that a majority of patients with expression of PD-L1 on tumor cells were included in the PD-L1 immune cell–positive population, with only 2% having PD-L1 expression exclusively on their tumor cells.

Data previously reported at the European Society for Medical Oncology and published in the New England Journal of Medicine showed a PFS benefit, as well as a clinically meaningful improvement in OS of nearly 10 months, specifically in patients with PD-L1 immune cell–positive lesions treated with atezolizumab + nab-paclitaxel, she noted.

“In data presented for the first time today you can see that PD-L1–negative patients derive no overall survival benefit as there was no treatment effect with this therapy combination,” she said.

A trend was seen toward an association between immune cell positivity and poor prognosis, but this was not statistically significant, she said.

“Taken together, these data definitively show that PD-L1 immune cell positivity is predictive of both progression-free and overall survival benefit with atezolizumab + nab-paclitaxel,” she said.

She and her colleagues also looked at the level of PD-L1 expression in immune cells to assess whether there is a threshold that might be required.

“As long as there was a PD-L1 expression level of 1% or more in the immune cells, there was a significant progression-free and overall survival benefit for patients treated with atezolizumab + nab-paclitaxel. This suggests that this expression of over 1% will represent a threshold for identifying those patients who are likely to benefit from this combination,” she said.

Further assessment by CD8 T-cell status showed that patients who had CD8-positive T cells but who were PD-L1 immune cell negative had no benefit from atezolizumab + nab-paclitaxel, whereas those who were positive for both CD8 and PD-L1 expression on their immune cells derived significant PFS and OS benefit (HR, 0.89 and 0.77, respectively).

“So patients with CD8-positive tumors derive clinical benefit only if their tumors are also PD-L1-positive,” she said.

Similarly, no clinical benefit was seen in patients with stromal tumor-infiltrating lymphocyte (TIL)–positive tumors but who were PD-L1-negative, whereas those with stromal TIL-positive PD-L1–positive tumors derived significant PFS and OS benefit (HRs, 0.99 and 1.53, respectively), and this was also seen in the 15% of evaluable patients who had BRCA mutations.

“In patients who were BRCA mutated, but who were PD-L1 immune cell negative, there was no association of progression-free survival or an overall survival benefit [with atezolizumab + nab-paclitaxel]. In contrast, in patients who were BRCA mutated but PD-L1 immune cell positive ... there was an association with progression-free survival and a trend toward overall survival,” she said, noting that while the BRCA mutation findings are limited by small numbers, “they do show that mutations in BRCA and PD-L1 expression in immune cells are independent biomarkers; patients with BRCA1 or 2 mutations derive clinical benefit only if their tumors are also PD-L1 positive.”

“In this phase 3 IMpassion130 study, PD-L1 expression on immune cells is a predictive biomarker for selecting patients who benefit clinically during first-line treatment with atezolizumab + nab-paclitaxel for metastatic triple-negative breast cancer,” she concluded, adding that “patients with newly diagnosed metastatic and unresectable locally advanced triple-negative breast cancer should be routinely tested for their PD-L1 immune cell status to determine if they might benefit from the combination of atezolizumab + nab-paclitaxel.

IMpassion130 was sponsored by Hoffman-La Roche. Dr. Emens reported receiving royalties and consulting fees from several companies. She has contracts with Roche/Genentech, Corvus, AstraZeneca, and EMD Serono, and ownership in Molecuvax. She receives other support from DSMB and Syndax, and has received grants from Aduro Biotech, Merck, Maxcyte, and the Breast Cancer Research Foundation. She also reported serving as a member of the Food and Drug Administration Advisory Committee on Tissue, Cell, and Gene Therapies, and is a member of the board of directors for the Society of Immunotherapy for Cancer.

SOURCE: Emens L et al. SABCS 2018, Abstract GS1-04.

SAN ANTONIO – Programmed death-ligand 1 (PD-L1) expression on tumor-infiltrating immune cells is the best predictor of response to atezolizumab + nab-paclitaxel in patients with untreated metastatic triple-negative breast cancer, according to exploratory efficacy analyses of data from the phase 3 IMpassion130 trial.

The analyses of data for the 902 patients randomized to receive the PD-L1 inhibitor atezolizumab (Tecentriq) plus nanoparticle albumin-bound (nab)–paclitaxel or placebo plus nab-palcitaxel for the study also showed consistency between local and central estrogen-receptor, progesterone-receptor, and human epidermal growth factor–receptor 2 testing, Leisha A. Emens, MD, reported at the San Antonio Breast Cancer Symposium.

“IMpassion130 is the first phase 3 study to demonstrate a benefit from [atezolizumab + nab-paclitaxel] in metastatic triple-negative breast cancer (mTNBC),” said Dr. Emens, professor of medicine in hematology/oncology, coleader of the Hillman Cancer Immunology and Immunotherapy Program, and director of translational immunotherapy for the Women’s Cancer Research Center at the University of Pittsburgh Medical Center.

She explained that progression-free survival (PFS) was significantly better in PD-L1–positive mTNBC patients treated with the atezolizumab + nab-paclitaxel, than in those who received placebo + nab-paclitaxel (hazard ratios in the intent-to-treat population, 0.8 and 0.62, respectively).

At the first interim overall survival analysis, a clinically meaningful improvement in OS was seen in PD-L1–positive patients in the treatment group (HR, 0.62; median OS improvement from 15.5 months with placebo to 25 months), she added.

In exploratory analyses, Dr. Emens and her colleagues sought to evaluate whether preexisting immune biology is associated with clinical benefit from atezolizumab + nab-paclitaxel, as has been demonstrated in studies of other agents that target the PD-1 pathway in other cancer types of cancer. They also assessed BRCA 1/2 mutation status as a biomarker for response.

“In patients enrolled on the IMpassion130 trial we found that PD-L1 in triple-negative breast cancer was expressed primarily on tumor-infiltrating immune cells,” she said. “In contrast to this, we found a very low rate of PD-L1 expression specifically on tumor cells across the patient population.”

Looking at both of those biomarkers together showed that a majority of patients with expression of PD-L1 on tumor cells were included in the PD-L1 immune cell–positive population, with only 2% having PD-L1 expression exclusively on their tumor cells.

Data previously reported at the European Society for Medical Oncology and published in the New England Journal of Medicine showed a PFS benefit, as well as a clinically meaningful improvement in OS of nearly 10 months, specifically in patients with PD-L1 immune cell–positive lesions treated with atezolizumab + nab-paclitaxel, she noted.

“In data presented for the first time today you can see that PD-L1–negative patients derive no overall survival benefit as there was no treatment effect with this therapy combination,” she said.

A trend was seen toward an association between immune cell positivity and poor prognosis, but this was not statistically significant, she said.

“Taken together, these data definitively show that PD-L1 immune cell positivity is predictive of both progression-free and overall survival benefit with atezolizumab + nab-paclitaxel,” she said.

She and her colleagues also looked at the level of PD-L1 expression in immune cells to assess whether there is a threshold that might be required.

“As long as there was a PD-L1 expression level of 1% or more in the immune cells, there was a significant progression-free and overall survival benefit for patients treated with atezolizumab + nab-paclitaxel. This suggests that this expression of over 1% will represent a threshold for identifying those patients who are likely to benefit from this combination,” she said.

Further assessment by CD8 T-cell status showed that patients who had CD8-positive T cells but who were PD-L1 immune cell negative had no benefit from atezolizumab + nab-paclitaxel, whereas those who were positive for both CD8 and PD-L1 expression on their immune cells derived significant PFS and OS benefit (HR, 0.89 and 0.77, respectively).

“So patients with CD8-positive tumors derive clinical benefit only if their tumors are also PD-L1-positive,” she said.

Similarly, no clinical benefit was seen in patients with stromal tumor-infiltrating lymphocyte (TIL)–positive tumors but who were PD-L1-negative, whereas those with stromal TIL-positive PD-L1–positive tumors derived significant PFS and OS benefit (HRs, 0.99 and 1.53, respectively), and this was also seen in the 15% of evaluable patients who had BRCA mutations.

“In patients who were BRCA mutated, but who were PD-L1 immune cell negative, there was no association of progression-free survival or an overall survival benefit [with atezolizumab + nab-paclitaxel]. In contrast, in patients who were BRCA mutated but PD-L1 immune cell positive ... there was an association with progression-free survival and a trend toward overall survival,” she said, noting that while the BRCA mutation findings are limited by small numbers, “they do show that mutations in BRCA and PD-L1 expression in immune cells are independent biomarkers; patients with BRCA1 or 2 mutations derive clinical benefit only if their tumors are also PD-L1 positive.”

“In this phase 3 IMpassion130 study, PD-L1 expression on immune cells is a predictive biomarker for selecting patients who benefit clinically during first-line treatment with atezolizumab + nab-paclitaxel for metastatic triple-negative breast cancer,” she concluded, adding that “patients with newly diagnosed metastatic and unresectable locally advanced triple-negative breast cancer should be routinely tested for their PD-L1 immune cell status to determine if they might benefit from the combination of atezolizumab + nab-paclitaxel.

IMpassion130 was sponsored by Hoffman-La Roche. Dr. Emens reported receiving royalties and consulting fees from several companies. She has contracts with Roche/Genentech, Corvus, AstraZeneca, and EMD Serono, and ownership in Molecuvax. She receives other support from DSMB and Syndax, and has received grants from Aduro Biotech, Merck, Maxcyte, and the Breast Cancer Research Foundation. She also reported serving as a member of the Food and Drug Administration Advisory Committee on Tissue, Cell, and Gene Therapies, and is a member of the board of directors for the Society of Immunotherapy for Cancer.

SOURCE: Emens L et al. SABCS 2018, Abstract GS1-04.

SAN ANTONIO – Programmed death-ligand 1 (PD-L1) expression on tumor-infiltrating immune cells is the best predictor of response to atezolizumab + nab-paclitaxel in patients with untreated metastatic triple-negative breast cancer, according to exploratory efficacy analyses of data from the phase 3 IMpassion130 trial.

The analyses of data for the 902 patients randomized to receive the PD-L1 inhibitor atezolizumab (Tecentriq) plus nanoparticle albumin-bound (nab)–paclitaxel or placebo plus nab-palcitaxel for the study also showed consistency between local and central estrogen-receptor, progesterone-receptor, and human epidermal growth factor–receptor 2 testing, Leisha A. Emens, MD, reported at the San Antonio Breast Cancer Symposium.

“IMpassion130 is the first phase 3 study to demonstrate a benefit from [atezolizumab + nab-paclitaxel] in metastatic triple-negative breast cancer (mTNBC),” said Dr. Emens, professor of medicine in hematology/oncology, coleader of the Hillman Cancer Immunology and Immunotherapy Program, and director of translational immunotherapy for the Women’s Cancer Research Center at the University of Pittsburgh Medical Center.

She explained that progression-free survival (PFS) was significantly better in PD-L1–positive mTNBC patients treated with the atezolizumab + nab-paclitaxel, than in those who received placebo + nab-paclitaxel (hazard ratios in the intent-to-treat population, 0.8 and 0.62, respectively).

At the first interim overall survival analysis, a clinically meaningful improvement in OS was seen in PD-L1–positive patients in the treatment group (HR, 0.62; median OS improvement from 15.5 months with placebo to 25 months), she added.

In exploratory analyses, Dr. Emens and her colleagues sought to evaluate whether preexisting immune biology is associated with clinical benefit from atezolizumab + nab-paclitaxel, as has been demonstrated in studies of other agents that target the PD-1 pathway in other cancer types of cancer. They also assessed BRCA 1/2 mutation status as a biomarker for response.

“In patients enrolled on the IMpassion130 trial we found that PD-L1 in triple-negative breast cancer was expressed primarily on tumor-infiltrating immune cells,” she said. “In contrast to this, we found a very low rate of PD-L1 expression specifically on tumor cells across the patient population.”

Looking at both of those biomarkers together showed that a majority of patients with expression of PD-L1 on tumor cells were included in the PD-L1 immune cell–positive population, with only 2% having PD-L1 expression exclusively on their tumor cells.

Data previously reported at the European Society for Medical Oncology and published in the New England Journal of Medicine showed a PFS benefit, as well as a clinically meaningful improvement in OS of nearly 10 months, specifically in patients with PD-L1 immune cell–positive lesions treated with atezolizumab + nab-paclitaxel, she noted.

“In data presented for the first time today you can see that PD-L1–negative patients derive no overall survival benefit as there was no treatment effect with this therapy combination,” she said.

A trend was seen toward an association between immune cell positivity and poor prognosis, but this was not statistically significant, she said.

“Taken together, these data definitively show that PD-L1 immune cell positivity is predictive of both progression-free and overall survival benefit with atezolizumab + nab-paclitaxel,” she said.

She and her colleagues also looked at the level of PD-L1 expression in immune cells to assess whether there is a threshold that might be required.

“As long as there was a PD-L1 expression level of 1% or more in the immune cells, there was a significant progression-free and overall survival benefit for patients treated with atezolizumab + nab-paclitaxel. This suggests that this expression of over 1% will represent a threshold for identifying those patients who are likely to benefit from this combination,” she said.

Further assessment by CD8 T-cell status showed that patients who had CD8-positive T cells but who were PD-L1 immune cell negative had no benefit from atezolizumab + nab-paclitaxel, whereas those who were positive for both CD8 and PD-L1 expression on their immune cells derived significant PFS and OS benefit (HR, 0.89 and 0.77, respectively).

“So patients with CD8-positive tumors derive clinical benefit only if their tumors are also PD-L1-positive,” she said.

Similarly, no clinical benefit was seen in patients with stromal tumor-infiltrating lymphocyte (TIL)–positive tumors but who were PD-L1-negative, whereas those with stromal TIL-positive PD-L1–positive tumors derived significant PFS and OS benefit (HRs, 0.99 and 1.53, respectively), and this was also seen in the 15% of evaluable patients who had BRCA mutations.

“In patients who were BRCA mutated, but who were PD-L1 immune cell negative, there was no association of progression-free survival or an overall survival benefit [with atezolizumab + nab-paclitaxel]. In contrast, in patients who were BRCA mutated but PD-L1 immune cell positive ... there was an association with progression-free survival and a trend toward overall survival,” she said, noting that while the BRCA mutation findings are limited by small numbers, “they do show that mutations in BRCA and PD-L1 expression in immune cells are independent biomarkers; patients with BRCA1 or 2 mutations derive clinical benefit only if their tumors are also PD-L1 positive.”

“In this phase 3 IMpassion130 study, PD-L1 expression on immune cells is a predictive biomarker for selecting patients who benefit clinically during first-line treatment with atezolizumab + nab-paclitaxel for metastatic triple-negative breast cancer,” she concluded, adding that “patients with newly diagnosed metastatic and unresectable locally advanced triple-negative breast cancer should be routinely tested for their PD-L1 immune cell status to determine if they might benefit from the combination of atezolizumab + nab-paclitaxel.

IMpassion130 was sponsored by Hoffman-La Roche. Dr. Emens reported receiving royalties and consulting fees from several companies. She has contracts with Roche/Genentech, Corvus, AstraZeneca, and EMD Serono, and ownership in Molecuvax. She receives other support from DSMB and Syndax, and has received grants from Aduro Biotech, Merck, Maxcyte, and the Breast Cancer Research Foundation. She also reported serving as a member of the Food and Drug Administration Advisory Committee on Tissue, Cell, and Gene Therapies, and is a member of the board of directors for the Society of Immunotherapy for Cancer.

SOURCE: Emens L et al. SABCS 2018, Abstract GS1-04.

SAN ANTONIO – A phase 3 randomized controlled trial jointly conducted by GEICAM and CIBOMA is negative, showing that adding adjuvant capecitabine (Xeloda) to surgery and standard chemotherapy does not improve disease-free or overall survival in women with early-stage triple-negative breast cancer, reported lead investigator Miguel Martín, MD, PhD.

At the San Antonio Breast Cancer Symposium, he discussed the overall findings and intriguing subgroup results suggesting that there was a benefit in women with tumors having the nonbasal phenotype. Dr. Martín also detailed implications in the context of the CREATE-X trial findings and the era of personalized medicine, and outlined next avenues of research.

The trial was supported by Roche, which also provided capecitabine. Dr. Martín disclosed that he has received speakers honoraria from Pfizer and Lilly; honoraria for participation in advisory boards from AstraZeneca, Novartis, Roche-Genentech, Pfizer, GlaxoSmithKline, PharmaMar, Taiho Oncology, and Lilly; and research grants from Novartis and Roche.

SAN ANTONIO – A phase 3 randomized controlled trial jointly conducted by GEICAM and CIBOMA is negative, showing that adding adjuvant capecitabine (Xeloda) to surgery and standard chemotherapy does not improve disease-free or overall survival in women with early-stage triple-negative breast cancer, reported lead investigator Miguel Martín, MD, PhD.

At the San Antonio Breast Cancer Symposium, he discussed the overall findings and intriguing subgroup results suggesting that there was a benefit in women with tumors having the nonbasal phenotype. Dr. Martín also detailed implications in the context of the CREATE-X trial findings and the era of personalized medicine, and outlined next avenues of research.

The trial was supported by Roche, which also provided capecitabine. Dr. Martín disclosed that he has received speakers honoraria from Pfizer and Lilly; honoraria for participation in advisory boards from AstraZeneca, Novartis, Roche-Genentech, Pfizer, GlaxoSmithKline, PharmaMar, Taiho Oncology, and Lilly; and research grants from Novartis and Roche.

SAN ANTONIO – A phase 3 randomized controlled trial jointly conducted by GEICAM and CIBOMA is negative, showing that adding adjuvant capecitabine (Xeloda) to surgery and standard chemotherapy does not improve disease-free or overall survival in women with early-stage triple-negative breast cancer, reported lead investigator Miguel Martín, MD, PhD.

At the San Antonio Breast Cancer Symposium, he discussed the overall findings and intriguing subgroup results suggesting that there was a benefit in women with tumors having the nonbasal phenotype. Dr. Martín also detailed implications in the context of the CREATE-X trial findings and the era of personalized medicine, and outlined next avenues of research.

The trial was supported by Roche, which also provided capecitabine. Dr. Martín disclosed that he has received speakers honoraria from Pfizer and Lilly; honoraria for participation in advisory boards from AstraZeneca, Novartis, Roche-Genentech, Pfizer, GlaxoSmithKline, PharmaMar, Taiho Oncology, and Lilly; and research grants from Novartis and Roche.

SAN ANTONIO – After a 2-year follow-up, the efficacy and cardiac toxicity profile between CT-P6, a trastuzumab biosimilar candidate, and trastuzumab as neoadjuvant and then adjuvant therapy for patients with early HER2-positive breast cancer remains consistent with previous results.

Similarity in safety and efficacy at 1 year was previously demonstrated in the phase 3 trial, as well as similarity in cardiac toxicity at a median of 19 months. Updated disease-free survival, overall survival, and cardiac toxicity with a median follow-up of 2 years will be presented by Francisco J. Esteva, MD, PhD, of the Laura & Isaac Perlmutter Cancer Center at NYU Langone Health, New York, in a poster presentation at the San Antonio Breast Cancer Symposium.

For the trial, 549 patients with HER2-positive early breast cancer were randomized to receive CT-P6 (n = 271) or trastuzumab (n = 278) in combination with docetaxel (cycles 1-4) and 5-fluorouracil, epirubicin, and cyclophosphamide (cycles 5-8). CT-P6 or trastuzumab was administered at 8 mg/kg (cycle 1 only) followed by 6 mg/kg every 3 weeks. After surgery, patients received CT-P6 or trastuzumab monotherapy and then entered the follow-up period.

A total of 528 patients entered the follow-up period, with a median duration of 27 months. Disease-free and overall survival were similar in the two arms in both the per-protocol set and the intention-to-treat set. In the intention-to-treat set, the 2-year disease-free survival was 86% (95% confidence interval, 80%-90%) in the CT-P6 arm and 90% (95% CI, 85%-93%) in the trastuzumab arm. Two-year overall survival was 97% (95% CI, 93%-98%) in the CT-P6 arm and 98% (95% CI, 96%-99%) in the trastuzumab arm. Median disease-free and overall survival have not been reached, according to the abstract.

No new cases of heart failure were reported during the follow-up period. Left ventricular ejection fraction was similar in both arms. The efficacy and cardiac toxicity profile between CT-P6 and trastuzumab were consistent with published data.

“CT-P6 was consistently well tolerated with a similar cardiotoxicity profile to that of trastuzumab through a long duration of follow-up,” Dr. Esteva and authors said.

The study sponsor is Celltrion, maker of CT-P6. Dr. Esteva disclosed a consulting or advisory role with Celltrion, as well as relationships with various other pharmaceutical companies.

SOURCE: Esteva FJ et al. SABCS 2018, Abstract P6-17-03.

SAN ANTONIO – After a 2-year follow-up, the efficacy and cardiac toxicity profile between CT-P6, a trastuzumab biosimilar candidate, and trastuzumab as neoadjuvant and then adjuvant therapy for patients with early HER2-positive breast cancer remains consistent with previous results.

Similarity in safety and efficacy at 1 year was previously demonstrated in the phase 3 trial, as well as similarity in cardiac toxicity at a median of 19 months. Updated disease-free survival, overall survival, and cardiac toxicity with a median follow-up of 2 years will be presented by Francisco J. Esteva, MD, PhD, of the Laura & Isaac Perlmutter Cancer Center at NYU Langone Health, New York, in a poster presentation at the San Antonio Breast Cancer Symposium.

For the trial, 549 patients with HER2-positive early breast cancer were randomized to receive CT-P6 (n = 271) or trastuzumab (n = 278) in combination with docetaxel (cycles 1-4) and 5-fluorouracil, epirubicin, and cyclophosphamide (cycles 5-8). CT-P6 or trastuzumab was administered at 8 mg/kg (cycle 1 only) followed by 6 mg/kg every 3 weeks. After surgery, patients received CT-P6 or trastuzumab monotherapy and then entered the follow-up period.

A total of 528 patients entered the follow-up period, with a median duration of 27 months. Disease-free and overall survival were similar in the two arms in both the per-protocol set and the intention-to-treat set. In the intention-to-treat set, the 2-year disease-free survival was 86% (95% confidence interval, 80%-90%) in the CT-P6 arm and 90% (95% CI, 85%-93%) in the trastuzumab arm. Two-year overall survival was 97% (95% CI, 93%-98%) in the CT-P6 arm and 98% (95% CI, 96%-99%) in the trastuzumab arm. Median disease-free and overall survival have not been reached, according to the abstract.

No new cases of heart failure were reported during the follow-up period. Left ventricular ejection fraction was similar in both arms. The efficacy and cardiac toxicity profile between CT-P6 and trastuzumab were consistent with published data.

“CT-P6 was consistently well tolerated with a similar cardiotoxicity profile to that of trastuzumab through a long duration of follow-up,” Dr. Esteva and authors said.

The study sponsor is Celltrion, maker of CT-P6. Dr. Esteva disclosed a consulting or advisory role with Celltrion, as well as relationships with various other pharmaceutical companies.

SOURCE: Esteva FJ et al. SABCS 2018, Abstract P6-17-03.

SAN ANTONIO – After a 2-year follow-up, the efficacy and cardiac toxicity profile between CT-P6, a trastuzumab biosimilar candidate, and trastuzumab as neoadjuvant and then adjuvant therapy for patients with early HER2-positive breast cancer remains consistent with previous results.

Similarity in safety and efficacy at 1 year was previously demonstrated in the phase 3 trial, as well as similarity in cardiac toxicity at a median of 19 months. Updated disease-free survival, overall survival, and cardiac toxicity with a median follow-up of 2 years will be presented by Francisco J. Esteva, MD, PhD, of the Laura & Isaac Perlmutter Cancer Center at NYU Langone Health, New York, in a poster presentation at the San Antonio Breast Cancer Symposium.

For the trial, 549 patients with HER2-positive early breast cancer were randomized to receive CT-P6 (n = 271) or trastuzumab (n = 278) in combination with docetaxel (cycles 1-4) and 5-fluorouracil, epirubicin, and cyclophosphamide (cycles 5-8). CT-P6 or trastuzumab was administered at 8 mg/kg (cycle 1 only) followed by 6 mg/kg every 3 weeks. After surgery, patients received CT-P6 or trastuzumab monotherapy and then entered the follow-up period.

A total of 528 patients entered the follow-up period, with a median duration of 27 months. Disease-free and overall survival were similar in the two arms in both the per-protocol set and the intention-to-treat set. In the intention-to-treat set, the 2-year disease-free survival was 86% (95% confidence interval, 80%-90%) in the CT-P6 arm and 90% (95% CI, 85%-93%) in the trastuzumab arm. Two-year overall survival was 97% (95% CI, 93%-98%) in the CT-P6 arm and 98% (95% CI, 96%-99%) in the trastuzumab arm. Median disease-free and overall survival have not been reached, according to the abstract.

No new cases of heart failure were reported during the follow-up period. Left ventricular ejection fraction was similar in both arms. The efficacy and cardiac toxicity profile between CT-P6 and trastuzumab were consistent with published data.

“CT-P6 was consistently well tolerated with a similar cardiotoxicity profile to that of trastuzumab through a long duration of follow-up,” Dr. Esteva and authors said.

The study sponsor is Celltrion, maker of CT-P6. Dr. Esteva disclosed a consulting or advisory role with Celltrion, as well as relationships with various other pharmaceutical companies.

SOURCE: Esteva FJ et al. SABCS 2018, Abstract P6-17-03.

SAN ANTONIO – Swapping trastuzumab out for the drug-antibody conjugate trastuzumab emtansine (T-DM1; Kadcyla) as adjuvant therapy resulted in a halving in the risk of invasive disease or death in patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy, including trastuzumab.

For the primary endpoint in the KATHERINE trial of invasive disease-free survival – defined as freedom from ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause – T-DM1 was associated with a hazard ratio of 0.50 (P less than .001).

The 3-year invasive disease-free survival rate for 743 patients treated with T-DMI 1 was 88.3%, compared with 77% for 743 patients treated with trastuzumab, reported Charles E. Geyer Jr., MD, from Virginia Commonwealth University, Richmond, at the San Antonio Breast Cancer Symposium.

In a video interview, Dr. Geyer discussed results of KATHERINE, which suggest that T-DM1 should be considered as a new standard of care in this patient population.

Dr. Geyer reported travel support from Roche and AstraZeneca, medical writing support from AbbVie and Roche, and honoraria from Celgene.

SAN ANTONIO – Swapping trastuzumab out for the drug-antibody conjugate trastuzumab emtansine (T-DM1; Kadcyla) as adjuvant therapy resulted in a halving in the risk of invasive disease or death in patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy, including trastuzumab.

For the primary endpoint in the KATHERINE trial of invasive disease-free survival – defined as freedom from ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause – T-DM1 was associated with a hazard ratio of 0.50 (P less than .001).

The 3-year invasive disease-free survival rate for 743 patients treated with T-DMI 1 was 88.3%, compared with 77% for 743 patients treated with trastuzumab, reported Charles E. Geyer Jr., MD, from Virginia Commonwealth University, Richmond, at the San Antonio Breast Cancer Symposium.

In a video interview, Dr. Geyer discussed results of KATHERINE, which suggest that T-DM1 should be considered as a new standard of care in this patient population.

Dr. Geyer reported travel support from Roche and AstraZeneca, medical writing support from AbbVie and Roche, and honoraria from Celgene.

SAN ANTONIO – Swapping trastuzumab out for the drug-antibody conjugate trastuzumab emtansine (T-DM1; Kadcyla) as adjuvant therapy resulted in a halving in the risk of invasive disease or death in patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy, including trastuzumab.

For the primary endpoint in the KATHERINE trial of invasive disease-free survival – defined as freedom from ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause – T-DM1 was associated with a hazard ratio of 0.50 (P less than .001).

The 3-year invasive disease-free survival rate for 743 patients treated with T-DMI 1 was 88.3%, compared with 77% for 743 patients treated with trastuzumab, reported Charles E. Geyer Jr., MD, from Virginia Commonwealth University, Richmond, at the San Antonio Breast Cancer Symposium.

In a video interview, Dr. Geyer discussed results of KATHERINE, which suggest that T-DM1 should be considered as a new standard of care in this patient population.

Dr. Geyer reported travel support from Roche and AstraZeneca, medical writing support from AbbVie and Roche, and honoraria from Celgene.

While the majority of the presentations at this year’s San Antonio Breast Cancer Symposium, to be held Dec. 4-8, will focus on treatments, a few will focus on the treatment decisions. One such presentation will report on the findings of the phase 3 STIC CTC trial. This trial seeks to determine if circulating tumor cells (CTC) could serve as a tool to choose between first-line hormone therapy and chemotherapy for ER-positive HER2-negative metastatic breast cancer.

In the standard arm of the trial, treatment was decided by clinicians, taking into account the criteria usually used in this setting. In the CTC arm, the type of treatment was decided by CTC count: Hormone-therapy was chosen if there were fewer than 5 CTC/7.5 mL (CellSearch technique) or chemotherapy if there were 5 or more CTC/7.5 mL. The main objective was to demonstrate the noninferiority of the CTC-based strategy for progression-free survival. The secondary clinical objectives of the French trial were to compare toxicity, quality of life, and overall survival between the two arms. The cost per progression-free life-years gained will be compared in the two arms, as well.

The results and analysis of STIC CTC will be presented by Francois-Clement Bidard, MD, PhD, of Institut Curie, Paris, and the University of Versailles (France), on Thursday, Dec. 6 at 11 a.m. CST.




 

While the majority of the presentations at this year’s San Antonio Breast Cancer Symposium, to be held Dec. 4-8, will focus on treatments, a few will focus on the treatment decisions. One such presentation will report on the findings of the phase 3 STIC CTC trial. This trial seeks to determine if circulating tumor cells (CTC) could serve as a tool to choose between first-line hormone therapy and chemotherapy for ER-positive HER2-negative metastatic breast cancer.

In the standard arm of the trial, treatment was decided by clinicians, taking into account the criteria usually used in this setting. In the CTC arm, the type of treatment was decided by CTC count: Hormone-therapy was chosen if there were fewer than 5 CTC/7.5 mL (CellSearch technique) or chemotherapy if there were 5 or more CTC/7.5 mL. The main objective was to demonstrate the noninferiority of the CTC-based strategy for progression-free survival. The secondary clinical objectives of the French trial were to compare toxicity, quality of life, and overall survival between the two arms. The cost per progression-free life-years gained will be compared in the two arms, as well.

The results and analysis of STIC CTC will be presented by Francois-Clement Bidard, MD, PhD, of Institut Curie, Paris, and the University of Versailles (France), on Thursday, Dec. 6 at 11 a.m. CST.




 

While the majority of the presentations at this year’s San Antonio Breast Cancer Symposium, to be held Dec. 4-8, will focus on treatments, a few will focus on the treatment decisions. One such presentation will report on the findings of the phase 3 STIC CTC trial. This trial seeks to determine if circulating tumor cells (CTC) could serve as a tool to choose between first-line hormone therapy and chemotherapy for ER-positive HER2-negative metastatic breast cancer.

In the standard arm of the trial, treatment was decided by clinicians, taking into account the criteria usually used in this setting. In the CTC arm, the type of treatment was decided by CTC count: Hormone-therapy was chosen if there were fewer than 5 CTC/7.5 mL (CellSearch technique) or chemotherapy if there were 5 or more CTC/7.5 mL. The main objective was to demonstrate the noninferiority of the CTC-based strategy for progression-free survival. The secondary clinical objectives of the French trial were to compare toxicity, quality of life, and overall survival between the two arms. The cost per progression-free life-years gained will be compared in the two arms, as well.

The results and analysis of STIC CTC will be presented by Francois-Clement Bidard, MD, PhD, of Institut Curie, Paris, and the University of Versailles (France), on Thursday, Dec. 6 at 11 a.m. CST.




 

Revisiting the old and enhancing with the new might describe the range of results in HER2+ breast cancer studies to be presented at the upcoming San Antonio Breast Cancer Symposium, which will be held Dec. 4-8 in San Antonio.

Since 2005, 12 months of trastuzumab added to chemotherapy alone has been the standard of care in patients with HER2-positive early breast cancer. PHARE (Protocol for Herceptin as Adjuvant Therapy With Reduced Exposure) was the first trial evaluating a reduced schedule of trastuzumab, a noninferiority trial comparing 6 with 12 months of adjuvant trastuzumab. Results published in 2013 in Lancet Oncology demonstrated a failure to prove that 6 months of treatment was non-inferior to 12 months. The final analysis of PHARE will be presented on Wednesday at SABCS 2018 by Xavier Pivot, MD, PhD, of Paul-Strauss Cancer Centre, Université de Strasbourg (France).

In a more recent study, trastuzumab emtansine (T-DM1) was pitted against trastuzumab as adjuvant therapy in patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy including trastuzumab. The primary results of the phase 3 study (KATHERINE) will be presented by Charles E. Geyer, MD, of Virginia Commonwealth University and the Massey Cancer Center, both in Richmond.

As for the new, KATE2 is a phase 2 randomized trial evaluating the addition of checkpoint inhibitor atezolizumab to T-DM1 for patients with locally advanced or metastatic HER2-positive breast cancer who received prior trastuzumab and taxane-based therapy. Results will be presented by Leisha A. Emens, MD, PhD, professor at the University of Pittsburgh and director of translational immunotherapy for the Women’s Cancer Research Center there.




 

Revisiting the old and enhancing with the new might describe the range of results in HER2+ breast cancer studies to be presented at the upcoming San Antonio Breast Cancer Symposium, which will be held Dec. 4-8 in San Antonio.

Since 2005, 12 months of trastuzumab added to chemotherapy alone has been the standard of care in patients with HER2-positive early breast cancer. PHARE (Protocol for Herceptin as Adjuvant Therapy With Reduced Exposure) was the first trial evaluating a reduced schedule of trastuzumab, a noninferiority trial comparing 6 with 12 months of adjuvant trastuzumab. Results published in 2013 in Lancet Oncology demonstrated a failure to prove that 6 months of treatment was non-inferior to 12 months. The final analysis of PHARE will be presented on Wednesday at SABCS 2018 by Xavier Pivot, MD, PhD, of Paul-Strauss Cancer Centre, Université de Strasbourg (France).

In a more recent study, trastuzumab emtansine (T-DM1) was pitted against trastuzumab as adjuvant therapy in patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy including trastuzumab. The primary results of the phase 3 study (KATHERINE) will be presented by Charles E. Geyer, MD, of Virginia Commonwealth University and the Massey Cancer Center, both in Richmond.

As for the new, KATE2 is a phase 2 randomized trial evaluating the addition of checkpoint inhibitor atezolizumab to T-DM1 for patients with locally advanced or metastatic HER2-positive breast cancer who received prior trastuzumab and taxane-based therapy. Results will be presented by Leisha A. Emens, MD, PhD, professor at the University of Pittsburgh and director of translational immunotherapy for the Women’s Cancer Research Center there.




 

Revisiting the old and enhancing with the new might describe the range of results in HER2+ breast cancer studies to be presented at the upcoming San Antonio Breast Cancer Symposium, which will be held Dec. 4-8 in San Antonio.

Since 2005, 12 months of trastuzumab added to chemotherapy alone has been the standard of care in patients with HER2-positive early breast cancer. PHARE (Protocol for Herceptin as Adjuvant Therapy With Reduced Exposure) was the first trial evaluating a reduced schedule of trastuzumab, a noninferiority trial comparing 6 with 12 months of adjuvant trastuzumab. Results published in 2013 in Lancet Oncology demonstrated a failure to prove that 6 months of treatment was non-inferior to 12 months. The final analysis of PHARE will be presented on Wednesday at SABCS 2018 by Xavier Pivot, MD, PhD, of Paul-Strauss Cancer Centre, Université de Strasbourg (France).

In a more recent study, trastuzumab emtansine (T-DM1) was pitted against trastuzumab as adjuvant therapy in patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy including trastuzumab. The primary results of the phase 3 study (KATHERINE) will be presented by Charles E. Geyer, MD, of Virginia Commonwealth University and the Massey Cancer Center, both in Richmond.

As for the new, KATE2 is a phase 2 randomized trial evaluating the addition of checkpoint inhibitor atezolizumab to T-DM1 for patients with locally advanced or metastatic HER2-positive breast cancer who received prior trastuzumab and taxane-based therapy. Results will be presented by Leisha A. Emens, MD, PhD, professor at the University of Pittsburgh and director of translational immunotherapy for the Women’s Cancer Research Center there.




 

Investigators presented results of the phase 3 IMpassion130 earlier this year demonstrating, for the first time, that a combination of an immune checkpoint inhibitor and a taxane provided significant clinical benefit to patients with advanced triple-negative breast cancer. However, the benefit was seen only in patients positive for programmed death-ligand 1 (PD-L1), the investigators reported at the annual congress of the European Society for Medical Oncology.

In the trial, 902 patients with untreated metastatic triple-negative breast cancer (mTNBC) were randomly assigned to receive the PD-L1 inhibitor atezolizumab (Tecentriq) plus nanoparticle albumin-bound (nab)–paclitaxel or placebo plus nab-paclitaxel. In an interim analysis, although there was no significant difference in median overall survival among all participants, atezolizumab was associated with a 38% improvement in median overall survival among patients with PD-L1–positive disease.

Additional analyses of the efficacy within immune biomarker subgroups in IMpassion130, including efficacy by BRCA status, will be presented at the upcoming 2018 San Antonio Breast Cancer Symposium, to be held Dec. 4-8 in San Antonio.

Leisha A. Emens, MD, PhD, professor of medicine in hematology/oncology, co-leader of the Hillman Cancer Immunology and Immunotherapy Program, and director of translational immunotherapy for the Women’s Cancer Research Center at the University of Pittsburgh Medical Center, will present the additional analyses on Wednesday, Dec. 5th at 9:30 a.m. CST.






 

Investigators presented results of the phase 3 IMpassion130 earlier this year demonstrating, for the first time, that a combination of an immune checkpoint inhibitor and a taxane provided significant clinical benefit to patients with advanced triple-negative breast cancer. However, the benefit was seen only in patients positive for programmed death-ligand 1 (PD-L1), the investigators reported at the annual congress of the European Society for Medical Oncology.

In the trial, 902 patients with untreated metastatic triple-negative breast cancer (mTNBC) were randomly assigned to receive the PD-L1 inhibitor atezolizumab (Tecentriq) plus nanoparticle albumin-bound (nab)–paclitaxel or placebo plus nab-paclitaxel. In an interim analysis, although there was no significant difference in median overall survival among all participants, atezolizumab was associated with a 38% improvement in median overall survival among patients with PD-L1–positive disease.

Additional analyses of the efficacy within immune biomarker subgroups in IMpassion130, including efficacy by BRCA status, will be presented at the upcoming 2018 San Antonio Breast Cancer Symposium, to be held Dec. 4-8 in San Antonio.

Leisha A. Emens, MD, PhD, professor of medicine in hematology/oncology, co-leader of the Hillman Cancer Immunology and Immunotherapy Program, and director of translational immunotherapy for the Women’s Cancer Research Center at the University of Pittsburgh Medical Center, will present the additional analyses on Wednesday, Dec. 5th at 9:30 a.m. CST.






 

Investigators presented results of the phase 3 IMpassion130 earlier this year demonstrating, for the first time, that a combination of an immune checkpoint inhibitor and a taxane provided significant clinical benefit to patients with advanced triple-negative breast cancer. However, the benefit was seen only in patients positive for programmed death-ligand 1 (PD-L1), the investigators reported at the annual congress of the European Society for Medical Oncology.

In the trial, 902 patients with untreated metastatic triple-negative breast cancer (mTNBC) were randomly assigned to receive the PD-L1 inhibitor atezolizumab (Tecentriq) plus nanoparticle albumin-bound (nab)–paclitaxel or placebo plus nab-paclitaxel. In an interim analysis, although there was no significant difference in median overall survival among all participants, atezolizumab was associated with a 38% improvement in median overall survival among patients with PD-L1–positive disease.

Additional analyses of the efficacy within immune biomarker subgroups in IMpassion130, including efficacy by BRCA status, will be presented at the upcoming 2018 San Antonio Breast Cancer Symposium, to be held Dec. 4-8 in San Antonio.

Leisha A. Emens, MD, PhD, professor of medicine in hematology/oncology, co-leader of the Hillman Cancer Immunology and Immunotherapy Program, and director of translational immunotherapy for the Women’s Cancer Research Center at the University of Pittsburgh Medical Center, will present the additional analyses on Wednesday, Dec. 5th at 9:30 a.m. CST.






 

Stereotactic radiosurgery (SRS) provides better early local control of brain metastases than complete surgical resection, but this advantage fades with time, according to investigators.

By 6 months, lower risks associated with SRS shifted in favor of those who had surgical resection, reported lead author Thomas Churilla, MD, of Fox Chase Cancer Center in Philadelphia and his colleagues.

“Outside recognized indications for surgery such as establishing diagnosis or relieving mass effect, little evidence is available to guide the therapeutic choice of SRS vs. surgical resection in the treatment of patients with limited brain metastases,” the investigators wrote in JAMA Oncology.

The investigators performed an exploratory analysis of data from the European Organization for the Research and Treatment of Cancer (EORTC) 22952-26001 phase 3 trial, which was designed to evaluate whole-brain radiotherapy for patients with one to three brain metastases who had undergone SRS or complete surgical resection. The present analysis involved 268 patients, of whom 154 had SRS and 114 had complete surgical resection.

Primary tumors included lung, breast, colorectum, kidney, and melanoma. Initial analysis showed that patients undergoing surgical resection, compared with those who had SRS, typically had larger brain metastases (median, 28 mm vs. 20 mm) and more often had 1 brain metastasis (98.2% vs. 74.0%). Mass locality also differed between groups; compared with patients receiving SRS, surgical patients more often had metastases in the posterior fossa (26.3% vs. 7.8%) and less often in the parietal lobe (18.4% vs. 39.6%).

After median follow-up of 39.9 months, risks of local recurrence were similar between surgical and SRS groups (hazard ratio, 1.15). Stratifying by interval, however, showed that surgical patients were at much higher risk of local recurrence in the first 3 months following treatment (HR for 0-3 months, 5.94). Of note, this risk faded with time (HR for 3-6 months, 1.37; HR for 6-9 months, 0.75; HR for 9 months or longer, 0.36). From the 6-9 months interval onward, surgical patients had lower risk of recurrence, compared with SRS patients, and the risk even decreased after the 6-9 month interval.

“Prospective controlled trials are warranted to direct the optimal local approach for patients with brain metastases and to define whether any population may benefit from escalation in local therapy,” the investigators concluded.

The study was funded by the National Cancer Institute, National Institutes of Health, and Fonds Cancer in Belgium. One author reported receiving financial compensation from Pfizer via her institution.

SOURCE: Churilla T et al. JAMA Onc. 2018. doi: 10.1001/jamaoncol.2018.4610.
 

Stereotactic radiosurgery (SRS) provides better early local control of brain metastases than complete surgical resection, but this advantage fades with time, according to investigators.

By 6 months, lower risks associated with SRS shifted in favor of those who had surgical resection, reported lead author Thomas Churilla, MD, of Fox Chase Cancer Center in Philadelphia and his colleagues.

“Outside recognized indications for surgery such as establishing diagnosis or relieving mass effect, little evidence is available to guide the therapeutic choice of SRS vs. surgical resection in the treatment of patients with limited brain metastases,” the investigators wrote in JAMA Oncology.

The investigators performed an exploratory analysis of data from the European Organization for the Research and Treatment of Cancer (EORTC) 22952-26001 phase 3 trial, which was designed to evaluate whole-brain radiotherapy for patients with one to three brain metastases who had undergone SRS or complete surgical resection. The present analysis involved 268 patients, of whom 154 had SRS and 114 had complete surgical resection.

Primary tumors included lung, breast, colorectum, kidney, and melanoma. Initial analysis showed that patients undergoing surgical resection, compared with those who had SRS, typically had larger brain metastases (median, 28 mm vs. 20 mm) and more often had 1 brain metastasis (98.2% vs. 74.0%). Mass locality also differed between groups; compared with patients receiving SRS, surgical patients more often had metastases in the posterior fossa (26.3% vs. 7.8%) and less often in the parietal lobe (18.4% vs. 39.6%).

After median follow-up of 39.9 months, risks of local recurrence were similar between surgical and SRS groups (hazard ratio, 1.15). Stratifying by interval, however, showed that surgical patients were at much higher risk of local recurrence in the first 3 months following treatment (HR for 0-3 months, 5.94). Of note, this risk faded with time (HR for 3-6 months, 1.37; HR for 6-9 months, 0.75; HR for 9 months or longer, 0.36). From the 6-9 months interval onward, surgical patients had lower risk of recurrence, compared with SRS patients, and the risk even decreased after the 6-9 month interval.

“Prospective controlled trials are warranted to direct the optimal local approach for patients with brain metastases and to define whether any population may benefit from escalation in local therapy,” the investigators concluded.

The study was funded by the National Cancer Institute, National Institutes of Health, and Fonds Cancer in Belgium. One author reported receiving financial compensation from Pfizer via her institution.

SOURCE: Churilla T et al. JAMA Onc. 2018. doi: 10.1001/jamaoncol.2018.4610.
 

Stereotactic radiosurgery (SRS) provides better early local control of brain metastases than complete surgical resection, but this advantage fades with time, according to investigators.

By 6 months, lower risks associated with SRS shifted in favor of those who had surgical resection, reported lead author Thomas Churilla, MD, of Fox Chase Cancer Center in Philadelphia and his colleagues.

“Outside recognized indications for surgery such as establishing diagnosis or relieving mass effect, little evidence is available to guide the therapeutic choice of SRS vs. surgical resection in the treatment of patients with limited brain metastases,” the investigators wrote in JAMA Oncology.

The investigators performed an exploratory analysis of data from the European Organization for the Research and Treatment of Cancer (EORTC) 22952-26001 phase 3 trial, which was designed to evaluate whole-brain radiotherapy for patients with one to three brain metastases who had undergone SRS or complete surgical resection. The present analysis involved 268 patients, of whom 154 had SRS and 114 had complete surgical resection.

Primary tumors included lung, breast, colorectum, kidney, and melanoma. Initial analysis showed that patients undergoing surgical resection, compared with those who had SRS, typically had larger brain metastases (median, 28 mm vs. 20 mm) and more often had 1 brain metastasis (98.2% vs. 74.0%). Mass locality also differed between groups; compared with patients receiving SRS, surgical patients more often had metastases in the posterior fossa (26.3% vs. 7.8%) and less often in the parietal lobe (18.4% vs. 39.6%).

After median follow-up of 39.9 months, risks of local recurrence were similar between surgical and SRS groups (hazard ratio, 1.15). Stratifying by interval, however, showed that surgical patients were at much higher risk of local recurrence in the first 3 months following treatment (HR for 0-3 months, 5.94). Of note, this risk faded with time (HR for 3-6 months, 1.37; HR for 6-9 months, 0.75; HR for 9 months or longer, 0.36). From the 6-9 months interval onward, surgical patients had lower risk of recurrence, compared with SRS patients, and the risk even decreased after the 6-9 month interval.

“Prospective controlled trials are warranted to direct the optimal local approach for patients with brain metastases and to define whether any population may benefit from escalation in local therapy,” the investigators concluded.

The study was funded by the National Cancer Institute, National Institutes of Health, and Fonds Cancer in Belgium. One author reported receiving financial compensation from Pfizer via her institution.

SOURCE: Churilla T et al. JAMA Onc. 2018. doi: 10.1001/jamaoncol.2018.4610.
 

Circulating tumor DNA could be effectively isolated from plasma by focusing on a particular range of fragment sizes, which paves the way for noninvasive genomic analysis of tumor DNA, new research suggests.

In a study of 344 plasma samples from 200 patients with 18 cancer types and 65 samples from healthy controls, DNA fragment length could be used to distinguish circulating tumor DNA (ctDNA) from other cell-free DNA (cfDNA), investigators reported in Science Translational Medicine.

“We hypothesized that we could improve the sensitivity for noninvasive cancer genomics by selective sequencing of ctDNA fragments and by leveraging differences in the biology that determine DNA fragmentation,” wrote Florent Mouliere, PhD, from the Cancer Research UK Cambridge Institute, and coauthors.

Cell-free plasma fragments are often cleaved at around 167 base pairs in length and differences in length between circulating fetal and maternal DNA are already used for noninvasive prenatal diagnosis. However, the authors said that only a few studies, with conflicting results, have looked at the size distribution of tumor-derived cfDNA.

The study used two approaches to determining the size profile of mutant ctDNA. The first looked at tumor and nontumor cfDNA in mice with human ovarian cancer xenografts and the second approach used deep sequencing in 19 cancer patients. This revealed that tumor-derived cfDNA was most commonly found in fragments between 90-150 base pairs or 250-320 base pairs in size.

The researchers also noted that mutant circulating tumor DNA was generally more fragmented than nonmutant cfDNA and that patients with untreated advanced cancer showed consistently shorter lengths of mutant DNA.

The next question was whether size selection and other biological properties – such as somatic alterations – of the cfDNA could be used to enhance detection of ctDNA via machine learning technology.

Two models, designed to distinguish between healthy and cancerous samples, were developed using 153 samples, then validated on two datasets of 94 and 83 samples.

One of these models correctly classified cancerous samples in 94% of samples from patients with cancers known to have high levels of ctDNA – colorectal, cholangiocarcinoma, ovarian, breast, and melanoma – and in 65% of samples from low-ctDNA cancers – pancreatic, renal, and glioma.

Another model focused just on fragmentation patterns and was still able to distinguish cancer samples from those of healthy controls, although with slightly reduced area under the curve.

“Our results indicate that exploiting fundamental properties of cfDNA with fragment-specific analyses can allow more sensitive evaluation of ctDNA,” the authors wrote. “We identified features that could determine the presence and amount of ctDNA in plasma samples, without a prior knowledge of somatic aberrations.”

The authors pointed out that size selection of DNA fragments was relatively simple and cheap, and was also compatible with other genome-wide and targeted genomic analyses, “greatly increasing the potential value and utility of liquid biopsies as well as the cost-effectiveness of cfDNA sequencing.”

However, they cautioned that their catalogue had focused solely on double-stranded DNA and was subject to potential biases from the DNA extraction and sequencing methods they used in the study. They also commented that other biological effects could help refine the analysis of ctDNA.

“Other bodily fluids [urine, cerebrospinal fluid, and saliva], different nucleic acids and structures, altered mechanisms of release into circulation, or sample processing methods could exhibit varying fragment size signatures and could offer additional exploitable biological patterns for selective sequencing,” they wrote.

The study was supported by the University of Cambridge, Cancer Research UK, and the Engineering and Physical Sciences Research Council. Research supporting the study was also funded by the European Research Council, the National Institute for Health Research Cambridge, National Cancer Research Network, Cambridge Experimental Cancer Medicine Centre, Hutchison Whampoa, Target Ovarian Cancer, the Medical Research Council, and AstraZeneca. Three authors are cofounders, shareholders, and officers/consultants in a company specializing in ctDNA analysis. One author declared research funding and advisory board fees from private industry. Seven authors are listed on related patents.

SOURCE: Mouliere F et al. Sci Transl Med. 2018 Nov 7. doi: 10.1126/scitranslmed.aat4921.
 

Circulating tumor DNA could be effectively isolated from plasma by focusing on a particular range of fragment sizes, which paves the way for noninvasive genomic analysis of tumor DNA, new research suggests.

In a study of 344 plasma samples from 200 patients with 18 cancer types and 65 samples from healthy controls, DNA fragment length could be used to distinguish circulating tumor DNA (ctDNA) from other cell-free DNA (cfDNA), investigators reported in Science Translational Medicine.

“We hypothesized that we could improve the sensitivity for noninvasive cancer genomics by selective sequencing of ctDNA fragments and by leveraging differences in the biology that determine DNA fragmentation,” wrote Florent Mouliere, PhD, from the Cancer Research UK Cambridge Institute, and coauthors.

Cell-free plasma fragments are often cleaved at around 167 base pairs in length and differences in length between circulating fetal and maternal DNA are already used for noninvasive prenatal diagnosis. However, the authors said that only a few studies, with conflicting results, have looked at the size distribution of tumor-derived cfDNA.

The study used two approaches to determining the size profile of mutant ctDNA. The first looked at tumor and nontumor cfDNA in mice with human ovarian cancer xenografts and the second approach used deep sequencing in 19 cancer patients. This revealed that tumor-derived cfDNA was most commonly found in fragments between 90-150 base pairs or 250-320 base pairs in size.

The researchers also noted that mutant circulating tumor DNA was generally more fragmented than nonmutant cfDNA and that patients with untreated advanced cancer showed consistently shorter lengths of mutant DNA.

The next question was whether size selection and other biological properties – such as somatic alterations – of the cfDNA could be used to enhance detection of ctDNA via machine learning technology.

Two models, designed to distinguish between healthy and cancerous samples, were developed using 153 samples, then validated on two datasets of 94 and 83 samples.

One of these models correctly classified cancerous samples in 94% of samples from patients with cancers known to have high levels of ctDNA – colorectal, cholangiocarcinoma, ovarian, breast, and melanoma – and in 65% of samples from low-ctDNA cancers – pancreatic, renal, and glioma.

Another model focused just on fragmentation patterns and was still able to distinguish cancer samples from those of healthy controls, although with slightly reduced area under the curve.

“Our results indicate that exploiting fundamental properties of cfDNA with fragment-specific analyses can allow more sensitive evaluation of ctDNA,” the authors wrote. “We identified features that could determine the presence and amount of ctDNA in plasma samples, without a prior knowledge of somatic aberrations.”

The authors pointed out that size selection of DNA fragments was relatively simple and cheap, and was also compatible with other genome-wide and targeted genomic analyses, “greatly increasing the potential value and utility of liquid biopsies as well as the cost-effectiveness of cfDNA sequencing.”

However, they cautioned that their catalogue had focused solely on double-stranded DNA and was subject to potential biases from the DNA extraction and sequencing methods they used in the study. They also commented that other biological effects could help refine the analysis of ctDNA.

“Other bodily fluids [urine, cerebrospinal fluid, and saliva], different nucleic acids and structures, altered mechanisms of release into circulation, or sample processing methods could exhibit varying fragment size signatures and could offer additional exploitable biological patterns for selective sequencing,” they wrote.

The study was supported by the University of Cambridge, Cancer Research UK, and the Engineering and Physical Sciences Research Council. Research supporting the study was also funded by the European Research Council, the National Institute for Health Research Cambridge, National Cancer Research Network, Cambridge Experimental Cancer Medicine Centre, Hutchison Whampoa, Target Ovarian Cancer, the Medical Research Council, and AstraZeneca. Three authors are cofounders, shareholders, and officers/consultants in a company specializing in ctDNA analysis. One author declared research funding and advisory board fees from private industry. Seven authors are listed on related patents.

SOURCE: Mouliere F et al. Sci Transl Med. 2018 Nov 7. doi: 10.1126/scitranslmed.aat4921.
 

Circulating tumor DNA could be effectively isolated from plasma by focusing on a particular range of fragment sizes, which paves the way for noninvasive genomic analysis of tumor DNA, new research suggests.

In a study of 344 plasma samples from 200 patients with 18 cancer types and 65 samples from healthy controls, DNA fragment length could be used to distinguish circulating tumor DNA (ctDNA) from other cell-free DNA (cfDNA), investigators reported in Science Translational Medicine.

“We hypothesized that we could improve the sensitivity for noninvasive cancer genomics by selective sequencing of ctDNA fragments and by leveraging differences in the biology that determine DNA fragmentation,” wrote Florent Mouliere, PhD, from the Cancer Research UK Cambridge Institute, and coauthors.

Cell-free plasma fragments are often cleaved at around 167 base pairs in length and differences in length between circulating fetal and maternal DNA are already used for noninvasive prenatal diagnosis. However, the authors said that only a few studies, with conflicting results, have looked at the size distribution of tumor-derived cfDNA.

The study used two approaches to determining the size profile of mutant ctDNA. The first looked at tumor and nontumor cfDNA in mice with human ovarian cancer xenografts and the second approach used deep sequencing in 19 cancer patients. This revealed that tumor-derived cfDNA was most commonly found in fragments between 90-150 base pairs or 250-320 base pairs in size.

The researchers also noted that mutant circulating tumor DNA was generally more fragmented than nonmutant cfDNA and that patients with untreated advanced cancer showed consistently shorter lengths of mutant DNA.

The next question was whether size selection and other biological properties – such as somatic alterations – of the cfDNA could be used to enhance detection of ctDNA via machine learning technology.

Two models, designed to distinguish between healthy and cancerous samples, were developed using 153 samples, then validated on two datasets of 94 and 83 samples.

One of these models correctly classified cancerous samples in 94% of samples from patients with cancers known to have high levels of ctDNA – colorectal, cholangiocarcinoma, ovarian, breast, and melanoma – and in 65% of samples from low-ctDNA cancers – pancreatic, renal, and glioma.

Another model focused just on fragmentation patterns and was still able to distinguish cancer samples from those of healthy controls, although with slightly reduced area under the curve.

“Our results indicate that exploiting fundamental properties of cfDNA with fragment-specific analyses can allow more sensitive evaluation of ctDNA,” the authors wrote. “We identified features that could determine the presence and amount of ctDNA in plasma samples, without a prior knowledge of somatic aberrations.”

The authors pointed out that size selection of DNA fragments was relatively simple and cheap, and was also compatible with other genome-wide and targeted genomic analyses, “greatly increasing the potential value and utility of liquid biopsies as well as the cost-effectiveness of cfDNA sequencing.”

However, they cautioned that their catalogue had focused solely on double-stranded DNA and was subject to potential biases from the DNA extraction and sequencing methods they used in the study. They also commented that other biological effects could help refine the analysis of ctDNA.

“Other bodily fluids [urine, cerebrospinal fluid, and saliva], different nucleic acids and structures, altered mechanisms of release into circulation, or sample processing methods could exhibit varying fragment size signatures and could offer additional exploitable biological patterns for selective sequencing,” they wrote.

The study was supported by the University of Cambridge, Cancer Research UK, and the Engineering and Physical Sciences Research Council. Research supporting the study was also funded by the European Research Council, the National Institute for Health Research Cambridge, National Cancer Research Network, Cambridge Experimental Cancer Medicine Centre, Hutchison Whampoa, Target Ovarian Cancer, the Medical Research Council, and AstraZeneca. Three authors are cofounders, shareholders, and officers/consultants in a company specializing in ctDNA analysis. One author declared research funding and advisory board fees from private industry. Seven authors are listed on related patents.

SOURCE: Mouliere F et al. Sci Transl Med. 2018 Nov 7. doi: 10.1126/scitranslmed.aat4921.
 

BOSTON – For women undergoing nipple-sparing mastectomy, advanced age and neoadjuvant chemotherapy are not associated with increased postoperative complications, results of recent studies suggest.

Andrew D. Bowser/MDedge News

The procedure was “surgically safe” in older patients, with complication rates comparable to those seen in younger patients, Solange E. Cox, MD, of MedStar Georgetown University Hospital, Washington, said in a presentation of one those two retrospective analyses at the annual clinical congress of the American College of Surgeons.

“From this, we think that eligible older patients should be offered a nipple-sparing mastectomy as a surgical option for breast cancer, and age alone should not be used as criteria to exclude these patients from the option,” she said.

The second retrospective study showed that patients undergoing neoadjuvant chemotherapy had a rate of surgical complications and unintended reoperations comparable to what was seen in women undergoing primary surgery.

“Our big-picture takeaway from this study is that receipt of neoadjuvant chemotherapy is not a contraindication for nipple-sparing mastectomy,” said investigator Alex J. Bartholomew, MS, also of Medstar Georgetown University Hospital.

Mr. Bartholomew’s conclusion was based on an analysis of the nipple-sparing mastectomy registry of the American Society of Breast Surgeons that included a total of 3,125 breasts. Neoadjuvant chemotherapy was used in 528, or 16.9%, while primary surgery was performed in 2,597, or 83.1%.

The overall rate of complications was 11%, with nonsignificant differences between the neoadjuvant chemotherapy and primary surgery groups at 12.7% and 10.7%, respectively.

Andrew D. Bowser/MDedge News

SOURCES: Cox S et al. SF310 abstract; Bartholomew AJ et al. SF310 abstract ACS Clinical Congress 2018

BOSTON – For women undergoing nipple-sparing mastectomy, advanced age and neoadjuvant chemotherapy are not associated with increased postoperative complications, results of recent studies suggest.

Andrew D. Bowser/MDedge News

The procedure was “surgically safe” in older patients, with complication rates comparable to those seen in younger patients, Solange E. Cox, MD, of MedStar Georgetown University Hospital, Washington, said in a presentation of one those two retrospective analyses at the annual clinical congress of the American College of Surgeons.

“From this, we think that eligible older patients should be offered a nipple-sparing mastectomy as a surgical option for breast cancer, and age alone should not be used as criteria to exclude these patients from the option,” she said.

The second retrospective study showed that patients undergoing neoadjuvant chemotherapy had a rate of surgical complications and unintended reoperations comparable to what was seen in women undergoing primary surgery.

“Our big-picture takeaway from this study is that receipt of neoadjuvant chemotherapy is not a contraindication for nipple-sparing mastectomy,” said investigator Alex J. Bartholomew, MS, also of Medstar Georgetown University Hospital.

Mr. Bartholomew’s conclusion was based on an analysis of the nipple-sparing mastectomy registry of the American Society of Breast Surgeons that included a total of 3,125 breasts. Neoadjuvant chemotherapy was used in 528, or 16.9%, while primary surgery was performed in 2,597, or 83.1%.

The overall rate of complications was 11%, with nonsignificant differences between the neoadjuvant chemotherapy and primary surgery groups at 12.7% and 10.7%, respectively.

Andrew D. Bowser/MDedge News

SOURCES: Cox S et al. SF310 abstract; Bartholomew AJ et al. SF310 abstract ACS Clinical Congress 2018

BOSTON – For women undergoing nipple-sparing mastectomy, advanced age and neoadjuvant chemotherapy are not associated with increased postoperative complications, results of recent studies suggest.

Andrew D. Bowser/MDedge News

The procedure was “surgically safe” in older patients, with complication rates comparable to those seen in younger patients, Solange E. Cox, MD, of MedStar Georgetown University Hospital, Washington, said in a presentation of one those two retrospective analyses at the annual clinical congress of the American College of Surgeons.

“From this, we think that eligible older patients should be offered a nipple-sparing mastectomy as a surgical option for breast cancer, and age alone should not be used as criteria to exclude these patients from the option,” she said.

The second retrospective study showed that patients undergoing neoadjuvant chemotherapy had a rate of surgical complications and unintended reoperations comparable to what was seen in women undergoing primary surgery.

“Our big-picture takeaway from this study is that receipt of neoadjuvant chemotherapy is not a contraindication for nipple-sparing mastectomy,” said investigator Alex J. Bartholomew, MS, also of Medstar Georgetown University Hospital.

Mr. Bartholomew’s conclusion was based on an analysis of the nipple-sparing mastectomy registry of the American Society of Breast Surgeons that included a total of 3,125 breasts. Neoadjuvant chemotherapy was used in 528, or 16.9%, while primary surgery was performed in 2,597, or 83.1%.

The overall rate of complications was 11%, with nonsignificant differences between the neoadjuvant chemotherapy and primary surgery groups at 12.7% and 10.7%, respectively.

Andrew D. Bowser/MDedge News

SOURCES: Cox S et al. SF310 abstract; Bartholomew AJ et al. SF310 abstract ACS Clinical Congress 2018