Dr. Ciombor on Rechallenging With EGFR Inhibitors in RAS/RAF Wild-Type CRC

Kristen K. Ciombor, MD, MSCI, associate professor of medicine, Division of Hematology/Oncology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, discusses data evaluating the utility of rechallenging with EGFR inhibitors in RAS/RAF wild-type colorectal cancer (CRC).

Several clinical trials have been published or are ongoing that are evaluating the utility of rechallenging with EGFR inhibitors in patients with RAS/RAF wild-type CRC, Ciombor explains. The data from these studies are providing insight into optimizing the use of EGFR inhibitors in patients who progress following prior treatment with EGFR inhibitors.

For example, the phase 2 CRICKET study (NCT02296203) evaluated rechallenging with cetuximab (Erbitux) in irinotecan-pretreated patients with KRAS, NRAS, and BRAF wild-type, metastatic CRC (mCRC) who were treated with an EGFR inhibitor in the first-line setting. The results of the study demonstrated a 21% response rate among 28 evaluable patients. Moreover, circulating tumor DNA (ctDNA) analysis of RAS mutational status was found to be helpful in selecting candidate patients, Ciombor explains.

The phase 2 CHRONOS trial (NCT03227926) evaluated rechallenging with panitumumab (Vectibix) in a similar patient population; the results demonstrated a 30% response rate among 27 evaluable patients. In this study as well, ctDNA was found to be helpful in identifying candidate patients for retreatment with the EGFR inhibitor, Ciombor says.

The phase 2 CAVE trial (NCT04561336) evaluated the combination of avelumab (Bavencio) plus cetuximab in patients with RAS wild-type mCRC who responded to first-line chemotherapy plus an EGFR inhibitor, developed acquired resistance, and progressed on second-line treatment. The results demonstrated a median overall survival of 11.6 months and a median progression-free survival of 3.6 months with the combination. The results also suggested that ctDNA testing before treatment may inform optimal patient selection.

The ongoing, prospective phase 2 PULSE trial (NCT03992456) is currently enrolling patients with metastatic or unresectable, RAS wild-type CRC. Patients will be randomized to rechallenge with panitumumab vs standard of care regorafenib (Stivarga) or TAS-102 (trifluridine/tipiracil; Lonsurf), Ciombor concludes.