Prevalence and characterization of dermatologic adverse events related to alpelisib (BYL719) in breast cancer patients

1063 Background: Rash develops in approximately 50% of breast cancer patients receiving alpelisib, often requiring dose modifications. Herein, we describe the characteristics of alpelisib-related dermatologic adverse events (dAEs). Methods: A single center retrospective analysis was conducted via review of electronic medical records. We collected clinical, laboratory and management data relevant to patients treated with alpelisib for advanced breast cancer under four different randomized clinical trials or post approval by regulatory agencies from 6/1/2013 to 7/31/2019. Type and severity of dAEs was recorded using the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). Results: A total of 102 patients (mean age 56 years, range 27-83) receiving alpelisib from 200 to 350 mg daily, most frequently in combination with endocrine therapy (79, 77.5%) were included. We identified 41 (40.2%) patients with all-grade rash [CTCAE grade 1/2 = 22 (21.6%); CTCAE grade 3 = 19, (18.6%)] distributed primarily along the trunk (18, 78%) and developing, on average, within 12.8 +/- 1.5 days of treatment initiation (n = 38). Mean duration of rash was 7.1 +/- 3.8 days; and no grade 4 dAEs were observed. Of 29 patients with documented morphology of alpelisib-related dAEs, the majority (26, 89.7%) had maculopapular rash. Thirteen (68%) of 19 patients with any-grade rash and report of any associated symptoms had pruritus (7, 36%) or burning pain (6, 32%). All-grade dAEs correlated with an increase in serum eosinophils from 2.7% to 4.4% (p < 0.05), and prophylaxis with non-sedating antihistamines (n = 43) was correlated with a reduction of grade 1/2 rash onset (OR 0.39, p = 0.09). Sixteen (84.2%) of 19 patients with grade 3 dAEs had interruption of alpelisib, followed by management with antihistamines, topical and/or systemic corticosteroids. We did not observe rash recurrence in 12 (75%) of these 16 patients who re-initiated therapy; and the majority (9, 56.3%) were re-challenged without a dose reduction. Conclusions: Pruritus and increased blood eosinophils occur with maculopapular rash within the first two weeks of initiating alpelisib and persists for approximately seven days. To reduce onset of grade 1/2 rash, non-sedating antihistamines (i.e. cetirizine) are recommended during the first eight weeks. While grade 3 rash leads to interruption of alpelisib, dermatologic improvement is evident with systemic corticosteroids; and most patients can resume therapy at a maintained or reduced dose upon re-challenge.