The end-of-study analysis of the landmark CLEOPATRA trial shows that 37% of patients with HER2-positive metastatic breast cancer are still alive at 8 years, according to principal investigator Sandra M. Swain, MD, FACP, FASCO, Associate Dean for Research Development at Georgetown University Medical Center and the Lombardi Comprehensive Cancer Center, Washington, DC, who presented the results at the 2019 ASCO Annual Meeting.1
Over one-third of patients who would have died years ago without HER2-targeted treatment are now alive at 8 years. The question now is when to stop treatment?— Sandra M. Swain, MD, FACP, FASCO
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The unprecedented overall survival improvement earlier shown with a first-line regimen of pertuzumab, trastuzumab, and docetaxel was maintained after an additional 4 years of long-term follow-up, as were the safety and cardiac safety profiles, she reported.
“These are ‘knock-your-socks-off’ data! There’s never been another study in metastatic breast cancer to show anywhere near this kind of survival benefit with this length of follow-up,” Dr. Swain said in an interview with The ASCO Post. “As of November 2018, the data cutoff, 59 patients are still on study and have not progressed. It’s a possibility—though I hesitate to use the word—that these patients are cured,” she commented.
The global phase III CLEOPATRA trial randomly assigned 808 patients to first-line treatment with pertuzumab combined with trastuzumab/docetaxel, or trastuzumab/docetaxel alone. In 2015, Dr. Swain and colleagues reported an unprecedented absolute 15.7-month increase in overall survival with the triplet, compared with the control arm.2 After a median follow-up of 50 months,
median overall survival was 56.5 months and 40.8 months, respectively—a 32% reduction in mortality (hazard ratio [HR] = 0.68; P < .001) at the time.
At the ASCO Annual Meeting, Dr. Swain reported the end-of-study analysis, which occurred after a median follow-up of 99 months. The maximum follow-up was 120 months.
Since July 2012, 50 patients have crossed over from placebo to the pertuzumab arm. Those patients were counted in the placebo arm for efficacy analyses and up to the first dose of pertuzumab for the safety analysis, which is a conservative analysis.
Large Survival Benefit Upheld in End-of-Study Analysis
Median overall survival was 57.1 months in the pertuzumab/trastuzumab arm and 40.8 months in the placebo arm—an absolute difference of 16.3 months favoring dual anti-HER2 blockade. The 8-year landmark overall survival rates were 37% and 23%, respectively, Dr. Swain reported at the ASCO meeting.
The overall survival benefit in predefined subgroups, including in patients previously treated with trastuzumab in the adjuvant or neoadjuvant setting, remained consistent with the overall result and the previous report. The reduction in the risk of death among patients previously treated with trastuzumab was 14%.
Safety Profile Also Upheld
The overall safety profile of the triplet was consistent with the known safety profile of pertuzumab. “There was only one new serious adverse event, suggestive of congestive heart failure, since the previous analysis,” she said. “Its onset was about 77 months after starting treatment in the pertuzumab arm, and it resolved in 34 days, with the patient continuing on study medication.” One patient also had new symptomatic left-ventricular systolic dysfunction, which began about 46 months after the patient crossed over to the pertuzumab arm and resolved in 34 days.
“These are spectacular results. Over one-third of patients who would have died years ago without HER2-targeted treatment are now alive at 8 years. The question now is when to stop treatment?” Dr. Swain said. “As of November, many patients were still on HER2-targeted treatment in this trial, and we see the same thing in our clinical practices. Patients often don’t want to stop treatment.” ■
DISCLOSURE: Dr. Swain has consulted or advised for Cardinal Health, Daiichi -Sankyo, Genentech/Roche, Genomic Health, Inivata, Lilly, Pieris Pharmaceuticals, and Tocagen and has received honoraria from Novartis; travel expenses from Caris Centers of Excellence, Daiichi-Sankyo, Genentech/Roche, Inivata, Lilly, and -NanoString Technologies; and institutional research funding from Genentech. She also reported other relationships with AstraZeneca and Roche.
1. Swain SM, Miles D, Kim S-B, et al: End-of-study analysis from the phase III, randomized, double-blind, placebo-controlled CLEOPATRA study of first-line pertuzumab, trastuzumab, and docetaxel in patients with HER2-positive metastatic breast cancer. 2019 ASCO Annual Meeting. Abstract 1020. Presented June 2, 2019.
2. Swain SM, Baselga J, Kim SB, et al: Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med 372:724-734, 2015.
John T. Cole, MD
“The end-of-study analysis of the CLEOPATRA trial demonstrates and confirms the long-term benefit of combined HER2-antibody therapy, with a significant number of ongoing responders,” said John T. Cole, MD, breast cancer specialist and Director of Clinical Cancer Research at...