A Phase II Feasibility Study of Palbociclib in Combination with Adjuvant Endocrine Therapy for Hormone Receptor Positive Invasive Breast Carcinoma
Mené sur 162 patients atteints d'un cancer du sein HR+ de stade précoce, cet essai de phase II évalue la faisabilité, du point de vue de l'arrêt anticipé du traitement à cause de sa toxicité, de la non-adhésion au traitement ou de la survenue d'événements indésirables, d'un traitement adjuvant par palbociclib dispensé pendant 2 ans en combinaison avec une hormonothérapie
Background : The CDK4/6 inhibitor palbociclib prolongs progression-free survival in hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancer when combined with endocrine therapy. This phase II trial was designed to determine the feasibility of adjuvant palbociclib and endocrine therapy for early breast cancer. Patients and Methods : Eligible patients with HR+/HER2- stage II-III breast cancer received 2 years of palbociclib at 125 mg daily, 3 weeks on/1 week off, with endocrine therapy. The primary endpoint was discontinuation from palbociclib due to toxicity, non-adherence, or events related to tolerability. A discontinuation rate of 48% or higher would indicate the treatment duration of two years was not feasible, and was evaluated under a binomial test using a one-sided alpha=0.025. Results : Overall, 162 patients initiated palbociclib; over half had stage III disease (52%) and most received prior chemotherapy (80%). A total of 102 patients (63%) completed 2 years of palbociclib; 50 patients discontinued early for protocol-related reasons (31%, 95%CI 24–39%, p = 0.001), and 10 discontinued due to protocol-unrelated reasons. The cumulative incidence of protocol-related discontinuation was 21% (95%CI 14–27%) at 12 months from start of treatment. Rates of palbociclib-related toxicity were congruent with the metastatic experience, and there were no cases of febrile neutropenia. Ninety-one patients (56%) required at least one dose reduction. Conclusion : Adjuvant palbociclib is feasible in early breast cancer, with a high proportion of patients able to complete 2 years of therapy. The safety profile in the adjuvant setting mirrors that observed in metastatic disease, with approximately half of the patients requiring dose-modification. As extended duration adjuvant palbociclib appears feasible and tolerable for most patients, randomized phase III trials are evaluating clinical benefit in this population.