Erin Roesch, MD
Adjuvant endocrine therapy (ET) has been shown to reduce risk of recurrence and improve survival in HR+ early breast cancer (EBC). A retrospective matched cohort analysis of 1,972 patients ≥70 years of age with HR+/HER2-negative, node-negative EBC and multiple medical co-morbidities, demonstrated higher median overall survival (OS) in patients who received ET versus those who did not (79.2 months compared to 67.7 months, p<0.0001). Older women with multiple medical co-morbidities may be at greater risk of toxicities related to ET, which can impact quality of life and adherence. The probability of initiating ET has been shown to be greater among patients who underwent radiation, thus highlighting the need to identify those who will adhere to ET when making decisions regarding radiation therapy to optimize care. ET should be discussed with all women who are candidates for this therapy, with a focus on individualized benefit and risk of these agents.
Studies of immunotherapy in metastatic triple-negative breast cancer have shown promising results, notably in patients with PD-L1 enriched tumors (IMpassion 130 and KEYNOTE-355). KEYNOTE-119 was a phase 3 study including 1,098 patients with metastatic TNBC who had received one or two previous systemic therapies for metastatic disease and progressed on most recent treatment, with randomization to pembrolizumab or physician’s choice chemotherapy . Median OS for pembrolizumab compared to chemotherapy was similar in the overall population (9.9 months versus 10.8 months, HR 0.97) and in patients with PD-L1 CPS score of ≥10 (12.7 months versus 11.6 months, HR 0.78, p=0.057). Although not statistically significant, greater PD-L1 expression was associated with longer median OS with pembrolizumab. Responses to immunotherapy may be durable in select patients, and these agents have an overall favorable toxicity profile. Novel immunotherapy combinations as well as biomarkers to predict response are certainly desired in this space.
Combination endocrine therapy plus a CDK 4/6 inhibitor is standard first-line treatment for metastatic HR+/HER2-negative breast cancer. Neutropenia is a common adverse event (AE) seen with the CDK 4/6 inhibitor palbociclib, and dosing guidelines provide a clear algorithm for drug monitoring and adjustment for cytopenias. Cutaneous toxicities, although not commonly seen, have been reported in the literature. Chawla and colleagues performed a retrospective analysis including 324 patients with advanced HR+/HER2-negative breast cancer who received palbociclib plus endocrine therapy. Cutaneous AEs were seen in 14.2%, with a significant proportion occurring early (41% occurred during or after the first cycle) and 50% resolved within 14 days (average 43 days). Of those who developed cutaneous AEs (n=46), only 15% and 4% required temporary hold and permanent cessation of therapy, respectively. These findings indicate a low overall incidence of cutaneous AEs associated with palbociclib, however highlight the importance of prompt recognition, management, and dermatology referral as appropriate, to help maintain patients on effective cancer-directed therapy.