Martin J. Edelman
CHICAGO — Palbociclib failed to reach a pre-specified response rate in patients with stage IV squamous cell lung cancer, according to results from a phase 2 study presented at the ASCO Annual Meeting.
“[Palbociclib] did not meet the level of activity necessary to advance to further testing, despite evaluating it in a molecularly defined population that would be the most likely to respond to the agent,” Martin J. Edelman, MD, chair of the department of hematology/oncology and deputy cancer center director for clinical research at Fox Chase Cancer Center, told HemOnc Today.
Edelman and colleagues aimed to assess the response rate to palbociclib (Ibrance, Pfizer) – a cyclin dependent kinase (CDK) 4/6 inhibitor approved for the treatment of advanced breast cancer – in patients with stage IV squamous cell lung cancer who presented with cell cycle gene abnormalities.
The study was originally designed as a phase 2/3 trial with the intent to compare palbociclib to docetaxel, but was modified to a two-stage phase 2 trial with a primary endpoint of a pre-specified response rate. The researchers had determined that if there were more than three responses within the first 20 patients, the study would then continue to 40 patients. The study would be deemed positive if 10 responses occurred in 40 patients.
Patients with a normal organ function and who had progressed after at least one prior platinum-based chemotherapy for any non-small cell lung cancer indication were eligible for study inclusion. Tumor specimens were required and evaluated for gene alterations and patients with CDK 4 or CCND1, CCND2 and CCND3 amplifications were eligible.
Fifty-three patients – 17 of whom received docetaxel – enrolled in the study. Eighty-three percent of patients presented with a CCND1 amplification, 13% had a CCND2 amplification, 9% presented with CCND3 and 6% had CDK4.
Five patients in the palbociclib arm (n = 37) were deemed ineligible for evaluation.
Two partial responses were identified among the 32 eligible patients (median age, 67; range 53-81 years; 21 male).
Thirty-eight percent of patients had a standard deviation and the disease control rate was 44%. Median PFS was 1.7 months.
One patient within the partial response arm has progressed with a duration of response of 7.7 months. Four patients reported a grade 4 adverse event and 13 others reported experiencing a grade 3 treatment-related adverse event.
“Even though we employed an active drug in a biomarker-defined population, the drug failed to demonstrate an adequate level of activity for advancement to the next stage of accrual,” Edelman said. “Interestingly, the two partial responses that were seen were in patients with CCND1 amplifications. If we had restricted eligibility to that abnormality, we might have met criteria for advancement. We are doing additional analyses regarding interactions of other molecular variables with activity, both in terms of response as well as survival. Unfortunately, with relatively small numbers, it will be difficult to draw any firm conclusions.” – by Ryan McDonald
Edelman MJ, et al. Abstract 9056. Presented at: ASCO Annual Meeting; June 2-6, 2017; Chicago.
Disclosures: Edelman reports serving as a consultant or advisor for ARIAD, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech/Roche, Lilly and Novartis; as well as research funding through his institution from Bristol-Myers Squibb, Endocyte, Genentech/Roche and Lilly.