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Treating older patients with chemotherapy is challenging. More research is needed to customize chemotherapy regimens, while balancing toxicities and efficacy in the geriatric population. With the advent of HER-2 targeted therapies such as trastuzumab, the strategy of de-escalation to avoid adjuvant chemotherapy altogether in older patients was examined by the RESPECT study group.

randomized older patients (age 70-80) in the adjuvant setting to receive trastuzumab monotherapy versus trastuzumab + chemotherapy. Notably, the majority of the patients (more than 80%) in the study had stages I or IIA disease. The primary objective of non-inferiority between the arms was not met.

The arm with chemotherapy and trastuzumab demonstrated a better 3-year disease-free survival (DFS) (93.8% vs 89.5%) when compared with the trastuzumab-monotherapy arm. However, the difference of restricted mean survival time for DFS between the arms was only 0.39 months at 3 years. The chemotherapy-free arm had a better toxicity profile, as well as better health-related quality of life.

The study, although limited by a short follow-up period and the relatively small sample size, nonetheless provides value in that there was quantification of benefit of chemotherapy in terms of survival, which would help clinicians and patients have a more informed conversations.

The decision to use chemotherapy in older patients is guided by performance status, comorbidities, and willingness to accept potential toxicities. The addition of chemotherapy to trastuzumab does appear to improve disease-free survival and relapse-free survival even within the 4-year follow-up period.

Therefore, it would be difficult to make a case to omit chemotherapy in fit older patients who may be able to tolerate some chemotherapy. The APT regimen studied by consisting of adjuvant paclitaxel and trastuzumab fared well with a 7-year DFS of 93%, 7-yr overall survival of 95%. The study established a regimen of less intense chemotherapy for patients with smaller tumors (3 cm or smaller).

This regimen could be used in fit older patients. And in frail older patients especially those older than 75, with lower-stage diseases with ER-positive disease, it would be reasonable to consider trastuzumab monotherapy. Importantly, when deciding on use of chemotherapy in the geriatric population, a comprehensive geriatric assessment should be used to better estimate the risks and benefits of therapy.

Rosana Gnanajothy, MD, is a hematology-medical oncology attending physician at Columbia University in New York City and part-time assistant professor of medicine at Bassett Medical Center, Mary Imogene Bassett Hospital, in Cooperstown, New York.

Read the study here and an interview about it here.