Durable responses to ADC sacituzumab in mTNBC

The novel antibody-drug conjugate sacituzumab govitecan was associated with durable clinical responses in one third of patients with heavily pretreated metastatic triple-negative breast cancer (TNBC), investigators in a multicenter study found.

Among a cohort of 108 patients with TNBC, the objective response rate (ORR) to treatment with sacituzumab govitecan was 33.3%, which included three complete and 33 partial responses (CR and PR), with a median duration of response of 7.7 months, reported Aditya Bardia, MD, from Massachusetts General Hospital in Boston and his colleagues.

“The duration of treatment with sacituzumab govitecan-hziy was longer than with the immediate previous antitumor therapy (5.1 months vs. 2.5 months); this provides further evidence of clinical activity in patients with difficult-to-treat metastatic triple-negative breast,” they wrote in The New England Journal of Medicine.

Sacituzumab govitecan (the suffix “hziy” used in the article is not sanctioned by the FDA, according to an editor’s note) is an antibody-drug conjugate consisting of SN-38, the active metabolite of the topoisomerase I inhibitor irinotecan, linked to a humanized monoclonal antibody targeted to Trop-2, a cell-surface glycoprotein expressed in triple-negative breast cancers and most other epithelial malignancies.

The study, preliminary results of which were previously reported at the San Antonio Breast Cancer Symposium in 2017, was part of a larger a phase 1/2 basket trial that resulted in sacituzumab govitecan receiving a breakthrough designation from the Food and Drug Administration.

The breast cancer cohort included 108 patients (107 women and one man; median age, 55 years) with TNBC who had received a median of 3 prior lines of anticancer therapies. Most had received taxanes (98%) and anthracyclines (86%).

At the time of data cutoff on December 1, 2017, the median duration of follow-up was 9.7 months. By that time, 100 of the 108 patients had discontinued therapy: 86 because of disease progression, three because of adverse events, 7 at the investigator’s discretion, and 2 for withdrawal of consent.

Four patients died during treatment; all of the deaths were judged to be caused by disease progression.

Grade 3 or 4 adverse events occurring in 10% or more of patients included neutropenia in 42% and anemia in 11%. Febrile neutropenia occurred in 9.3% of patients.

As noted before, the investigator-assessed ORR was 33.3%, and the median duration of response was 7.7 months. The ORR as assessed by independent central reviewers was 34.7%, and the median duration of response 9.1%. The clinical benefit rate, a composite of ORR plus stable disease of at a least 6 months duration, was 45.4%. The median progression-free survival was 5.5 months, and median overall survival was 13 months.

There were no significant differences in outcomes in a subgroup analysis broken down by patient age, metastatic disease, number of prior therapies, or presence of visceral metastases, the investigators noted, but they cautioned that the numbers were small, which led to wide confidence intervals, “and thus the homogeneity of clinical outcomes observed in these subgroups is weak and should be interpreted with caution,” they wrote.

The study was supported by Immunomedics. Dr. Bardia disclosed advisory board activities and institutional research grants from Immunomedics, Sanofi, and Radius Health. Multiple coauthors reported similar relationships with these and other companies.

SOURCE: Bardia A et al. NEJM 2019 Feb 20. doi: 10.1056/NEJMoa1814213.

The novel antibody-drug conjugate sacituzumab govitecan was associated with durable clinical responses in one third of patients with heavily pretreated metastatic triple-negative breast cancer (TNBC), investigators in a multicenter study found.

Among a cohort of 108 patients with TNBC, the objective response rate (ORR) to treatment with sacituzumab govitecan was 33.3%, which included three complete and 33 partial responses (CR and PR), with a median duration of response of 7.7 months, reported Aditya Bardia, MD, from Massachusetts General Hospital in Boston and his colleagues.

“The duration of treatment with sacituzumab govitecan-hziy was longer than with the immediate previous antitumor therapy (5.1 months vs. 2.5 months); this provides further evidence of clinical activity in patients with difficult-to-treat metastatic triple-negative breast,” they wrote in The New England Journal of Medicine.

Sacituzumab govitecan (the suffix “hziy” used in the article is not sanctioned by the FDA, according to an editor’s note) is an antibody-drug conjugate consisting of SN-38, the active metabolite of the topoisomerase I inhibitor irinotecan, linked to a humanized monoclonal antibody targeted to Trop-2, a cell-surface glycoprotein expressed in triple-negative breast cancers and most other epithelial malignancies.

The study, preliminary results of which were previously reported at the San Antonio Breast Cancer Symposium in 2017, was part of a larger a phase 1/2 basket trial that resulted in sacituzumab govitecan receiving a breakthrough designation from the Food and Drug Administration.

The breast cancer cohort included 108 patients (107 women and one man; median age, 55 years) with TNBC who had received a median of 3 prior lines of anticancer therapies. Most had received taxanes (98%) and anthracyclines (86%).

At the time of data cutoff on December 1, 2017, the median duration of follow-up was 9.7 months. By that time, 100 of the 108 patients had discontinued therapy: 86 because of disease progression, three because of adverse events, 7 at the investigator’s discretion, and 2 for withdrawal of consent.

Four patients died during treatment; all of the deaths were judged to be caused by disease progression.

Grade 3 or 4 adverse events occurring in 10% or more of patients included neutropenia in 42% and anemia in 11%. Febrile neutropenia occurred in 9.3% of patients.

As noted before, the investigator-assessed ORR was 33.3%, and the median duration of response was 7.7 months. The ORR as assessed by independent central reviewers was 34.7%, and the median duration of response 9.1%. The clinical benefit rate, a composite of ORR plus stable disease of at a least 6 months duration, was 45.4%. The median progression-free survival was 5.5 months, and median overall survival was 13 months.

There were no significant differences in outcomes in a subgroup analysis broken down by patient age, metastatic disease, number of prior therapies, or presence of visceral metastases, the investigators noted, but they cautioned that the numbers were small, which led to wide confidence intervals, “and thus the homogeneity of clinical outcomes observed in these subgroups is weak and should be interpreted with caution,” they wrote.

The study was supported by Immunomedics. Dr. Bardia disclosed advisory board activities and institutional research grants from Immunomedics, Sanofi, and Radius Health. Multiple coauthors reported similar relationships with these and other companies.

SOURCE: Bardia A et al. NEJM 2019 Feb 20. doi: 10.1056/NEJMoa1814213.

The novel antibody-drug conjugate sacituzumab govitecan was associated with durable clinical responses in one third of patients with heavily pretreated metastatic triple-negative breast cancer (TNBC), investigators in a multicenter study found.

Among a cohort of 108 patients with TNBC, the objective response rate (ORR) to treatment with sacituzumab govitecan was 33.3%, which included three complete and 33 partial responses (CR and PR), with a median duration of response of 7.7 months, reported Aditya Bardia, MD, from Massachusetts General Hospital in Boston and his colleagues.

“The duration of treatment with sacituzumab govitecan-hziy was longer than with the immediate previous antitumor therapy (5.1 months vs. 2.5 months); this provides further evidence of clinical activity in patients with difficult-to-treat metastatic triple-negative breast,” they wrote in The New England Journal of Medicine.

Sacituzumab govitecan (the suffix “hziy” used in the article is not sanctioned by the FDA, according to an editor’s note) is an antibody-drug conjugate consisting of SN-38, the active metabolite of the topoisomerase I inhibitor irinotecan, linked to a humanized monoclonal antibody targeted to Trop-2, a cell-surface glycoprotein expressed in triple-negative breast cancers and most other epithelial malignancies.

The study, preliminary results of which were previously reported at the San Antonio Breast Cancer Symposium in 2017, was part of a larger a phase 1/2 basket trial that resulted in sacituzumab govitecan receiving a breakthrough designation from the Food and Drug Administration.

The breast cancer cohort included 108 patients (107 women and one man; median age, 55 years) with TNBC who had received a median of 3 prior lines of anticancer therapies. Most had received taxanes (98%) and anthracyclines (86%).

At the time of data cutoff on December 1, 2017, the median duration of follow-up was 9.7 months. By that time, 100 of the 108 patients had discontinued therapy: 86 because of disease progression, three because of adverse events, 7 at the investigator’s discretion, and 2 for withdrawal of consent.

Four patients died during treatment; all of the deaths were judged to be caused by disease progression.

Grade 3 or 4 adverse events occurring in 10% or more of patients included neutropenia in 42% and anemia in 11%. Febrile neutropenia occurred in 9.3% of patients.

As noted before, the investigator-assessed ORR was 33.3%, and the median duration of response was 7.7 months. The ORR as assessed by independent central reviewers was 34.7%, and the median duration of response 9.1%. The clinical benefit rate, a composite of ORR plus stable disease of at a least 6 months duration, was 45.4%. The median progression-free survival was 5.5 months, and median overall survival was 13 months.

There were no significant differences in outcomes in a subgroup analysis broken down by patient age, metastatic disease, number of prior therapies, or presence of visceral metastases, the investigators noted, but they cautioned that the numbers were small, which led to wide confidence intervals, “and thus the homogeneity of clinical outcomes observed in these subgroups is weak and should be interpreted with caution,” they wrote.

The study was supported by Immunomedics. Dr. Bardia disclosed advisory board activities and institutional research grants from Immunomedics, Sanofi, and Radius Health. Multiple coauthors reported similar relationships with these and other companies.

SOURCE: Bardia A et al. NEJM 2019 Feb 20. doi: 10.1056/NEJMoa1814213.