Phase II Single-Arm Study of Palbociclib and Cetuximab Rechallenge in Patients with KRAS/NRAS/BRAF Wild-Type Colorectal Cancer

Jonathan D Sorah, Dominic T Moore, Matthew J Reilley, Mohamed E Salem, Tammy Triglianos, Hanna K Sanoff, Autumn J McRee, Michael S Lee, Jonathan D Sorah, Dominic T Moore, Matthew J Reilley, Mohamed E Salem, Tammy Triglianos, Hanna K Sanoff, Autumn J McRee, Michael S Lee

Abstract

Background: Cetuximab is often administered to patients with KRAS wild-type (KRAS-WT) metastatic colorectal cancer (mCRC), although resistance inevitably develops. We hypothesized that co-inhibition of the epidermal growth factor receptor (EGFR) with cetuximab and downstream cyclin-dependent kinases (CDK) 4/6 with palbociclib would be effective for anti-EGFR rechallenge in KRAS-WT mCRC.

Methods: We designed a single-arm, Simon's 2-stage, phase II trial of cetuximab and palbociclib in KRAS-WT mCRC treated with ≥2 prior lines of therapy. We report here on cohort B rechallenging patients with anti-EGFR-based therapy who had disease control of at least 4 months on prior anti-EGFR therapy. Primary endpoint was disease control rate (DCR) at 4 months.

Results: Ten evaluable patients were enrolled in this cohort. The 4-month DCR was 20%, which did not fulfill the prespecified 4-month DCR rate to continue. Median progression-free survival was 1.8 months and median overall survival was 6.6 months. Three patients had stable disease, although overall response rate was 0%. Most common treatment-related grades 3-4 adverse events were lymphopenia and leukopenia.

Conclusion: Selection of patients for anti-EGFR rechallenge using clinical criteria alone was insufficient to identify response to palbociclib + cetuximab. Additional biomarkers are needed to select anti-EGFR rechallenge and circulating tumor DNA (ctDNA) analysis is planned for samples collected in this study. (ClinicalTrials.gov Identifier: NCT03446157).

Keywords: KRAS wild type; anti-EGFR therapy; cetuximab; colorectal cancer; palbociclib.

Conflict of interest statement

Tammy Triglianos: Pfizer (C/A); Hanna K Sanoff: AstraZeneca, F. Hoffman La Roche, Amgen, Bristol-Myers Squibb, Pfizer, BioMed Valley Discoveries, Regenix, Exelixis (RF [institution]); Autumn J McRee: Biomed Valley Discoveries, Merck, Eli Lilly (RF), Merck (SAB), Janssen (E); Michael S. Lee: Imvax, G1 Therapeutics, Delcath, Pfizer (C/A); Repare, Arcus Bioscience, Merck, Erasca, Shanghai EpimAb (RF). The other authors indicated no financial relationships. (C/A) Consulting/advisory relationship; (RF) Research funding; (E) Employment; (ET) Expert testimony; (H) Honoraria received; (OI) Ownership interests; (IP) Intellectual property rights/inventor/patent holder; (SAB) Scientific advisory board.

© The Author(s) 2022. Published by Oxford University Press.

Figures

Figure 1.
Figure 1.
Kaplan-Meier plots for progression-free survival (top) and overall survival (bottom).
Figure 2.
Figure 2.
Waterfall plot.

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