Treatment-related neutropenia as predictor of response to adjuvant palbociclib in the PALLAS trial (ABCSG-42/AFT-05/BIG-14-13/PrE0109)

BACKGROUND: Prior analyses of PALLAS (NCT02513394), a phase III trial that randomized patients with stage II-III hormone receptor-positive breast cancer to receive adjuvant palbociclib plus endocrine therapy (ET) or ET alone, did not show benefit of the combination. Separate data show extent of treatment-related neutropenia is associated with improved response to palbociclib and other cell cycle-specific therapies. We conducted an exploratory analysis to assess whether grade of treatment-related neutropenia could identify benefit from palbociclib in the adjuvant setting. METHODS: Patients receiving palbociclib were classified into those with treatment-emergent high-grade neutropenia (HGN) with maximum grade ≥3 (absolute neutrophil count <1000/mm3), or low-grade/no neutropenia (LGN) with maximum grade ≤2. These groups were compared to each other and to the ET-alone group for 5-year invasive disease-free survival (iDFS). RESULTS: 5736 patients were included: 2840 in the palbociclib+ET arm and 2896 in the ET-alone arm. Patients receiving palbociclib+ET consisted of 1006 (35.4%) LGN and 1834 (64.6%) HGN. Lower body mass index (BMI), Asian race, prior chemotherapy, and mastectomy were associated with HGN (all p < 0.05). Patients receiving ET alone had inferior 5-year iDFS compared with patients who developed HGN by cycle 6 on palbociclib+ET (hazard ratio [HR] 1.19, 95% confidence interval [CI]:1.01-1.40; p = 0.04), an association that persisted after adjustment for prior chemotherapy, race, and BMI (HR 1.20, 95% CI:1.02-1.42; p = 0.03). CONCLUSION: In this exploratory analysis of the PALLAS trial, palbociclib+ET showed benefit over ET alone in patients who developed HGN in the first 6 treatment cycles. Neutropenia could be a useful biomarker for palbociclib efficacy. TRIAL REGISTRATION: clinicaltrials.gov, NCT02513394.