"These results highlight the issue of generalizability of clinical trial results to the real-world, as well as the need to re-evaluate the benefits of approved drugs when novel agents enter the treatment landscape," Dr. Josee-Lyne Ethier of Queen's University in Kingston, Ontario told Reuters Health by email.
"Approval of these agents transformed the treatment of patients with HER-2 positive breast cancer and they continue to be used as part of standard first- and second-line treatment in the metastatic setting," she said. "The efficacy-effectiveness gap observed with pertuzumab may be explained by the older age of real-world patients compared to those treated as part of CLEOPATRA," results of which were published in 2015. (https://bit.ly/3yMNusw)
In the EMILIA trial, published in 2012 (https://bit.ly/2TUbFGP), "participants treated with T-DM1 did not receive prior pertuzumab, which differs from most patients in routine practice," she added.
As reported in JAMA Oncology, Dr. Ethier and colleagues studied electronic health records of women with stage IV ERBB2-positive metastatic breast cancer receiving treatment with pertuzumab for first-line therapy from 2013-2017, and those treated withT-DM1 from 2014-2017. The primary outcome was overall survival (OS).
Records were analyzed for 795 women who received pertuzumab (median age, 57) and 506 who received T-DM1 (median age, 56). Among the entire cohort, the median OS was 43 months and the median time on treatment was 14 months.
In the T-DM1 group, the proportion of pertuzumab-naive patients decreased over time from 74.7% in 2014 to 18% in 2017. The median OS and time on treatment were 15 and 4 months, respectively.
For patients with prior pertuzumab treatment, the median OS was shorter than in the pertuzumab-naive subgroup (12 vs. 19 months; adjusted hazard ratio, 0.70).
By contrast, the median OS in the CLEOPATRA trial was 57 months, and in the EMILIA trial, 30 months.
Three oncologists commented in emails to Reuters Health, based on their own practices.
Dr. Anas Al-Janadi, Vice President and Department Chief, Spectrum Health Cancer Center in Michigan, noted, "In my experience, the differences can be explained by patient selection as we tend to offer FDA-approved drugs to sicker patients in the real world; adherence to approved dose and schedule (practicing oncologists tend to reduce doses, change schedule, hold treatments, etc.); and the level of support and close monitoring provided while on a clinical trial."
Dr. Haritha Pabbathi, medical oncologist and member of the Breast Cancer Center and Women's Cancer Center at CTCA Atlanta, said, "In my practice, most patients receive pertuzumab-based chemotherapy; therefore, it is less common for patients to be unexposed to pertuzumab when second-line therapy is indicated."
"I see clinical as well as radiological responses on TDM-1 and use this as a standard for second-line therapy," she noted. "The EMILIA trial has limitations, but TDM-1 is definitely my go-to second-line therapy."
"Clinical practice is changing quickly as new drugs are being approved and more data become available," she added. "Sometimes clinicians must rely on lagging data, or data that aren't up to date with what's happening in real time. The faster and more readily available the data, the better."
Dr. Stavroula Otis, a hematologist/oncologist with the Center for Cancer Prevention and Treatment at Providence St. Joseph Hospital in Orange, California, commented, "My patients with metastatic HER2-positive breast cancer are living longer and better because these drugs are so much more effective and less toxic than the chemotherapies we used in the past."
"I recommend clinicians continue using these highly effective new drugs, and rather than questioning their efficacy, we should be addressing the root cause of the efficacy-effectiveness gap, which is the selection of patients for clinical trials."
"I encourage academic and community physicians to support the initiative by ASCO and Friends of Cancer Research to expand access to clinical trials by broadening eligibility criteria (https://bit.ly/3e8xhG6), " Dr. Otis concluded.
SOURCE: https://bit.ly/3e9MYNn JAMA Oncology, online July 8, 2021.
By Marilynn Larkin
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