Episode 5: Unveiling Insights from the PALMIRA Trial: Continuing Palbociclib Beyond Progression in Metastatic Breast Cancer

The PALMIRA trial, a phase 2 open-label randomised study, sought answers to the pivotal question of whether continuing palbociclib beyond progression in metastatic breast cancer is clinically beneficial. Patients eligible for the trial exhibited disease progression after initial treatment with endocrine therapy and palbociclib. Subsequently, they were randomised into either a control arm receiving second-line endocrine therapy alone or an experimental arm receiving endocrine therapy combined with palbociclib. The choice of endocrine therapy in both arms was influenced by its compatibility with the first-line treatment.

The trial primarily focused on a second-line patient population, with the majority receiving fulvestrant as the endocrine therapy backbone. Unfortunately, the results revealed no statistically significant benefits from adding palbociclib to second-line endocrine therapy. Progression-free survival, a primary endpoint, did not exhibit statistical significance (4.9 vs. 3.6 months). Furthermore, objective response rate and overall survival demonstrated no improvements with the continued use of palbociclib.

A critical aspect highlighted by the trial was the prolonged treatment duration on first-line CDK4/6 inhibitors for about 80% of patients—more than one year. However, due to the trial’s size limitations, insights into potential benefits for patients with extended treatment durations remain unclear.

Comparisons with other trials, particularly the MAINTAIN trial, raised questions about the role of different CDK4/6 inhibitors. The PALMIRA and PACE trials, utilising the same CDK4/6 inhibitors, showed no significant benefits, while the MAINTAIN trial, using different inhibitors, reported positive outcomes. This suggests potential variations in the activity and safety profiles within the CDK4/6 inhibitor class.

Looking forward, these findings pose critical questions about the sequencing or switching of CDK4/6 inhibitors in the first-line treatment of hormone receptor-positive HER2-negative metastatic breast cancer, particularly for those previously exposed to these agents in the adjuvant setting.

In conclusion, while the PALMIRA trial results may be disappointing, they underscore the complexities surrounding the optimal use of CDK4/6 inhibitors in metastatic breast cancer. Ongoing research and clinical initiatives are essential for unravelling the intricacies of CDK4/6 inhibitor sequencing and improving treatment strategies for patients facing disease relapse despite prior adjuvant therapy.