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Shorter duration of trastuzumab noninferior for early-stage, HER-2-positive breast cancer
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Six months of treatment with trastuzumab appeared noninferior to 12 months of treatment among women with HER-2-positive early-stage breast cancer, according to a study scheduled for presentation at the ASCO Annual Meeting.
Additionally, fewer patients who received the shorter duration of therapy stopped treatment because of cardiotoxicity.
“In 2005 trastuzumab [Herceptin, Genentech] was licensed with a standard of three-weekly injections for 12 months as this was the duration used empirically in pivotal registration studies,” Helena Margaret Earl, MBBS, PhD, FRCP, professor of clinical cancer medicine at University of Cambridge in the U.K., said during a press conference. “A smaller study — FinHer with 232 patients, reported in 2006 —showed similar benefits for only 9 weeks of trastuzumab with 58% fewer cancer recurrences.”
Questions about the feasibility of shorter duration of trastuzumab therapy prompted Earl and colleagues to conduct the phase 3 randomized, U.K.-based PERSEPHONE trial.
The analysis compared 6 months (nine cycles) of trastuzumab to 12 months (18 cycles) of trastuzumab among 4,088 women with HER-2-positive, early-stage breast cancer.
Median follow-up was 4.9 years.
Researchers observed 319 deaths (8%) and 500 (12%) DFS events.
The 4-year DFS rate was 89% (95% CI, 88-91). Patients treated with 6 months of trastuzumab therapy demonstrated noninferior DFS compared with those treated for 12 months (number of DFS events, 265 vs. 247; HR = 1.07; 95% CI, 0.93-1.24).
Fewer patients stopped treatment due to cardiotoxicity in the 6-months group compared with the 12-months group (4% vs. 8%; P < .0001).
“Some of these heart problems are permanent,” Earl said. “But, what we see when we look at the whole population with left ventricular ejection fraction estimation is that there is a dip and a recovery. Cardiotoxicity in many women who suffer it does recover, but there are some women for whom that doesn’t happen.”
The most common grade 3 adverse events included cough, fatigue, pain, chills and palpitations, according to Earl.
Importantly, patients treated with 6 months of therapy may be able to return more quickly to their normal lives, Earl said.
Assessments of quality of life, patient-reported experience and health economics are ongoing.
“Important translational research will be carried out analyzing blood and tumor samples to look for biomarkers to identify subgroups of different risk where shorter or longer durations of trastuzumab might be tailored,” Earl said.
Researchers may not yet be able to determine whether these data will change standard of practice, Earl said.
“All of these results will have to have rigorous scientific scrutiny alongside other data that’re available,” she said. “What we’re saying at the moment is that we need to have a very detailed look at this group of patients. But we need to be very careful and cautious about coming out and saying 6 months is enough.”
Richard L. Schilsky, MD, FASCO, senior vice president and chief medical officer of ASCO, agreed longer follow-up is needed to allow these data to mature.
“We don’t have data yet on OS, but that will come with time,” he said during the press conference. “Undoubtedly, there may be some women in this population who don’t do as well with only 6 months of treatment, and the ongoing translational research may help identify which patients will do better with a longer course of treatment.
“Personally, I find the results quite compelling and I think it is likely that it will signal a shift —even in the U.S. oncology community — toward shorter duration of Herceptin adjuvant therapy,” he added. – by Cassie Homer
Reference:
Earl HM, et al. Abstract 506. Scheduled for presentation at: ASCO Annual Meeting; June 1-5, 2018; Chicago.
Disclosures: Earl reports consultant/advisory role with AstraZeneca, Celgene, Pfizer and Roche; travel accommodations/expenses from Amgen, AstraZeneca, Daiichi Sankyo and Pfizer; honoraria from Amgen, AstraZeneca, Daiichi Sankyo and Pfizer; and research funding from Roche and Sanofi. Please see the abstract for all other authors’ relevant financial disclosures.
Perspective
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Janice Lu, MD, PhD
PERSEPHONE is an important trial, and the largest one to date evaluating the impact of shortening the duration of adjuvant trastuzumab in HER-2-positive early-stage breast cancer. Although our current standard of care is to provide 12 months of treatment with trastuzumab, combined with pertuzumab (Perjeta, Genentech) for high-risk patients, based on recommendations from the APHINITY trial, this data challenges the standard of care and is asking the question whether less is more. This could be practice changing for many patients. However, we’d like to see the data stratifying patients with low-risk vs. high-risk disease, and whether 6 months of treatment with trastuzumab is noninferior to 12 months of treatment in both groups. The next step would be to assess the impact of treatment length on quality of life with quantitative feedback from the participants, as well as a detailed cost-effectiveness analysis, as mentioned by the study authors.
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