Dr Barot on Palbociclib Maintenance in HR+/HER2+ Metastatic Breast Cancer

“The addition of palbociclib did increase toxicity, particularly grade 3 or 4 neutropenia and diarrhea. However, we have been using palbociclib for a long time in the metastatic setting, and we have become familiar with how to manage these toxicities. Discontinuation [rates] were similar between the 2 groups, which is promising.”

Shimoli Barot, MD, a breast medical oncologist at Cleveland Clinic, discusses the efficacy and safety findings from the phase 3 PATINA trial (NCT02947685), which evaluated adding palbociclib (Ibrance) to maintenance HER2-directed therapy and endocrine therapy for patients with hormone receptor–positive, HER2-positive advanced or metastatic breast cancer whose disease had not progressed after prior chemotherapy plus HER2-directed therapy.

Barot emphasized that all patients enrolled in PATINA had hormone receptor–positive disease in addition to HER2-positive disease and consistently received endocrine therapy. This feature distinguishes PATINA from earlier trials of HER2-directed therapy, Barot noted. She explained that targeting both disease-driving pathways is important for treating patients in this population because the cancers are simultaneously dependent on hormone receptor and HER2 signaling.

In the control arm, maintenance trastuzumab (Herceptin), with or without pertuzumab (Perjeta), plus endocrine therapy (n = 257) produced a median progression-free survival (PFS) of 29.1 months (95% CI, 23.3-38.6). Adding palbociclib (n = 261) extended the median PFS to 44.3 months (95% CI, 32.4-56.8), an improvement of 15.2 months (HR, 0.75; 95% CI, 0.59-0.96; 2-sided unstratified P = .02). According to Barot, these findings reinforce the clinical value of continuously suppressing the endocrine pathway in this population.

The improvement in efficacy with the investigational regimen was accompanied by additional toxicity, Barot said. Neutropenia occurred in 77.8% of patients who received palbociclib compared with 7.7% of those who received HER2-directed and endocrine therapy without palbociclib. Diarrhea was also more frequent with the palbociclib-containing regimen. Barot identified grade 3 or 4 neutropenia and diarrhea as notable safety concerns.

However, Barot explained that extensive experience with administering palbociclib in the hormone receptor–positive metastatic breast cancer setting has increased familiarity with monitoring and managing these adverse effects. Treatment discontinuation rates remained relatively similar between the study groups despite the increased toxicity.