The CDK4/6 inhibitor palbociclib exhibited preliminary activity in patients with acral lentiginous melanoma associated with CDK-pathway aberrations, according to results of a small phase II trial that were reported at the 2019 ASCO Annual Meeting.
The CDK4/6 inhibitor palbociclib (Ibrance) exhibited preliminary activity in patients with acral lentiginous melanoma (ALM) associated with CDK-pathway aberrations, according to results of a small phase II trial that were reported at the 2019 ASCO Annual Meeting.
Findings showed that 1 of the 15 patients who received treatment with palbociclib attained a partial response (PR) within 8 weeks of starting on the CDK4/6 inhibitor, and 2 others had measurable tumor shrinkage. Overall, 3 patients had stable disease.
“Monotherapy with palbociclib demonstrated preliminary activity in advanced melanoma patients with CDK pathway gene aberrations; therefore, the study met its primary endpoint,” Lili Mao, MD, of Peking University Cancer Hospital & Institute in Beijing, and colleagues concluded in a poster presentation during the meeting. “Palbociclib had an acceptable safety profile consistent with previous studies. Combination therapy with a CDK4/6 inhibitor and other agents is under consideration.”
Genetic aberrations in the CDK4 pathway occur in 82% of patients with ALM, which is the predominant subtype of melanoma in China. The association provided the rationale for a phase II trial to evaluate the safety and efficacy of palbociclib in patients with ALM who harbor CDK-pathway alterations.
In the phase II trial, Mao and colleagues enrolled 15 patients with ALM associated with CDK4 amplification, CCND1 amplification, or CDKN2A loss—or a combination of these aberrations—from April 2018 to November 2018. Each patient received palbociclib 125 mg daily for the first 21 days of a 28-day cycle. Additionally, as determined with the trial design, there was a mandated termination if fewer than 2 patients had objective responses or stable disease after 8 weeks of treatment, which was the primary endpoint. Secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety.
The median age was 54 years (range, 25-74), and women accounted for a majority of the study population (N = 9). The most common site of the primary was subungual (N = 5), and 3 patients had stage III disease. The median lines of prior therapies was 2 (range, 0-5). Moreover, two-thirds of the patients had lung metastases, and most patients had multiple metastatic sites. All patients were included in the data analysis for safety, ORR, demographics, PFS, and OS.
As of April 2019, 2 patients remained on palbociclib. Results demonstrated that the median PFS was 2.5 months (range, 1.5-8.8), and the estimated median OS was 8.1 months (range, 6.7-9.4). Five patients died of disease progression during follow-up. The patient who had a PR had left plantar melanoma.
Regarding safety, the most common, all-grade treatment-related adverse events (TRAEs) were leukopenia/neutropenia (87%), thrombocytopenia (27%), and anemia (40%). Grade ≥3 TRAEs were comprised of leukopenia/neutropenia (33%), thrombocytopenia (7%), and anemia (7%).
Palbociclib was initially granted an accelerated approval by the FDA in combination with letrozole for the first-line treatment for postmenopausal female patients with estrogen receptor—positive, HER2-negative metastatic breast cancer in 2015, which was converted to a full approval in March 2017. In 2016, the FDA also approved palbociclib for use in combination with fulvestrant in pretreated patients with hormone receptor (HR)–positive, HER2-negative metastatic breast cancer.
Most recently, the FDA expanded the approval of palbociclib capsules in combination with endocrine therapy to include male patients with HR-positive, HER2-negative advanced or metastatic breast cancer.
Mao L, Cao Y, Sheng X, et al. Palbociclib (P) in advanced acral lentiginous melanoma (ALM) with CDK4 pathway gene aberrations. J Clin Oncol. 2019;37(suppl; abstr 9528). meetinglibrary.asco.org/record/176442/abstract.