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Trastuzumab with chemotherapy is standard adjuvant therapy for human epidermal growth factor receptor 2 (HER2)–positive primary breast cancer, but is this the right treatment for the increasing number of patients who are age 70 or older?

Clinical trial data in older patients is lacking, and these patients may have different needs and treatment goals, noted Masataka Sawaki, MD, PhD, of the Aichi Cancer Center in Nagoya, Japan, and co-authors, who recently reported results of the trial, which compared trastuzumab with chemotherapy with trastuzumab monotherapy in patients ages 70-80.

As the team noted in the study online in the , the primary objective of noninferiority for trastuzumab monotherapy in terms of disease-free survival was not met. However, the loss of survival without chemotherapy was less than 1 month at 3 years. Adverse events were lower with the monotherapy, and health-related quality of life (HRQoL), which may be especially important to older patients, was better.

"With lower toxicity and a better HRQoL profile, trastuzumab monotherapy can be a reasonable option for selected older patients with favorable outcomes," Sawaki and colleagues wrote.

In the following interview, Sawaki elaborated on the findings and discussed the implications.

Can you give an example of an older patient with HER2-positive breast cancer for whom trastuzumab monotherapy may be the best option?

Sawaki: We recommend trastuzumab monotherapy for patients older than 70 who need to avoid chemotherapy because of contraindications or patient preference, or patients over 75 with performance status 1 disease, estrogen-receptor positivity, and small node-negative disease, because in these patients loss of survival due to suppressing chemotherapy is small with lower toxicity and better health-related quality of life compared with trastuzumab plus chemotherapy.

Do you have any advice for discussing the trade-offs between survival and quality of life with older patients, or bringing the subject up?

Sawaki: It is a clinically important question. Detrimental effects of standard adjuvant chemotherapy in older patients on QoL, physical and functional well-being, morale, and activity capacity are not transient, but last for at least 12 months. In particular during the treatment period, the chemotherapy-induced peripheral neuropathy frequency was high. On the other hand, after 36 months there was no detrimental effects of chemotherapy for any QoL items.

It would be possible by adding these explanations to provide relief for patients seeking standard treatment with a combination of chemotherapy and trastuzumab. And also, for at least one year, care and social support will be required when adjuvant chemotherapy is given to older patients. (The findings on QoL in the RESPECT trial are now online in (Taira, Sawaki, et al.)

You mentioned that biomarkers will become important for identifying patients who would benefit from anti-HER2 therapy without chemotherapy. Can you tell us more about this?

Sawaki: Studies on biomarkers to predict benefit from anti-HER2 therapy without chemotherapy are important, but we do not have results on it.

You also mentioned that ASCO has proposed developing recommendations to improve the evidence base for treating older adults with cancer. Any more information about this effort?

Sawaki: There would be three important points. First, clinical trials for older patients with cancer are needed -- not only randomized controlled trials (RCTs), but also observation studies. If possible, collaboration with international research groups is also important.

Second, comprehensive geriatric assessment accompanying the clinical trial should be included. And finally, real-world data analysis by using national data bases is very important.

Is there anything else you want to make sure oncologists understand about the RESPECT trial?

Sawaki: We have not yet known whether or not adjuvant trastuzumab alone can offer benefit over no adjuvant therapy. In the RESPECT trial, trastuzumab monotherapy was compared with trastuzumab plus chemotherapy. Before starting the trial, we made an effort to directly compare trastuzumab monotherapy with no treatment by RCT, but we were afraid that such a design would not be feasible because patients might refuse such an arm that cannot receive trastuzumab despite HER2-positive disease.

Therefore, alternatively, we designed a cohort study accompanying the RESPECT trial and accumulated older patients with HER2-positive breast cancer who did not agree to participate in the RCT despite meeting the eligibility criteria.

We are just preparing the paper on results of the study, including patients with no adjuvant therapy.

Read the study here and expert commentary about the clinical implications here.