Treatment-related neutropenia as predictor of response to adjuvant palbociclib in the PALLAS trial (ABCSG-42/AFT-05/BIG-14-13/PrE0109)
Kristina Fanucci, Amylou C Dueck, Erica L Mayer, Miguel Martin, Tufia C Haddad, Nicholas Zdenkowski, Rupert Bartsch, Yelena Novik, Daniel Egle, Jennifer M Suga, Lois Shepherd, Tiffany A Traina, Elisabetta Munzone, Sibylle Loibl, Olwen Hahn, Meritxell Bellet-Ezquerra, Antonio C Wolff, Patrick Morris, Manuel Ruiz-Borrego, Zbigniew Nowecki, Norman Wolmark, Gabor Rubovsky, Claudine Isaacs, Ling-Min Tseng, Christian F Singer, Dhanusha Sabanathan, Theodoros Foukakis, Hiroji Iwata, Hope Rugo, Arlene Chan, Bettina Voetsch, Wamiq Zaidi, Sara Scovil, Christian Fesl, Patrick O’Brien, Dominik Hlauschek, Michael Gnant, Angela DeMicheleAbstract
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