The following article features coverage from the American Association for Cancer Research (AACR) 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Results from an analysis of patients with heavily pretreated advanced non-breast solid tumors characterized by amplification in CCND1, CCND2, or CCND3 receiving the cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor, palbociclib, in the National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) trial (ClinicalTrials.gov Identifier: NCT02465060) showed that the primary end point of objective response rate (ORR) in this population was not met. The findings were presented at the American Association for Cancer Research (AACR) Annual Meeting 2019.

The NCI-MATCH trial is a large, ongoing, nonrandomized, phase 2, precision medicine basket trial that was designed to determine whether specific targeted therapies are effective in patients with advanced, refractory cancers characterized by particular molecular alterations in tumors regardless of tumor type. 

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In the NCI-MATCH trial, eligible patients with advanced solid tumors, lymphoma, or multiple myeloma were enrolled in 1 of more than 30 treatment arms based on the molecular characteristics of their tumors. The primary objective of the study is ORR, with other study objectives including progression-free survival (PFS) at 6 months, and identification of potential predictive biomarkers. 

Forty patients were enrolled in the palbociclib/CCND1, CCND2, or CCND3 amplification arm of the NCI-MATCH study between August 2016 and December 2017; 39 of these patients had a somatic CCND1 amplification alteration, with CCND3 amplification observed in the tumor specimen of only 1 patient. 

In total, 36 patients, representing 23 different tumor histologies, were included in this analysis. The percentages of these patients who had received 3 or more and more than 4 lines of prior therapy was 70% and 42%, respectively. Rates of objective response and stable disease (SD) were 0% and 38.9%, respectively. Of the 14 patients achieving SD, 4 patients had SD lasting 6 cycles or longer (ie, prolonged SD), and 3 of these patients had received 2 lines of prior therapy or fewer. 

Median PFS was 1.8 months with an estimated 13% (90% CI, 5%-29%) of patients achieving a 6-month PFS. Interestingly, results from exploratory analyses showed that 2 of 3 patients with tumors containing a NOTCH1 mutation had prolonged SD.

While no new palbociclib safety signals were observed in this study, adverse events included anemia (67%), leukopenia (47%), neutropenia (44%), and fatigue (28%). The most common grade 3/4 adverse event was neutropenia, which was observed in 30.6% of patients. 

“CCND1 or [CCND]3 amplification may not predict response to palbociclib in this cohort,” the study authors concluded. 

Disclosure: The presenters have disclosed financial ties to various pharmaceutical companies. For a full list of disclosures, please see the original abstract.

Read more of Cancer Therapy Advisor‘s coverage of AACR 2019 meeting by visiting the conference page.

Reference

  1. Clark AS, Hong F, Finn RS, et al. Molecular analysis for therapy choice (NCI-MATCH, EAY131) arm Z1B: Phase II trial of palbociclib for CCND1, 2 or 3 amplified tumors. Presented at: American Association for Cancer Research (AACR) Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. Abstract LB-010/2.