KEY TAKEAWAYS
- The CAVE and CRICKET phase II study (NCT04561336) study registered under NCT04561336 aimed to determine the role of rechallenge with cetuximab. This drug inhibits EGFR in third-line RAS/BRAF wild-type metastatic colorectal cancer patients who had previously progressed on an anti-EGFR based-therapy.
- Researchers collected individual data from 33 and 13 patients from the CAVE and CRICKET trials, respectively, who received cetuximab rechallenge as third-line therapy.
- The study concluded that third-line cetuximab rechallenge in combination with either irinotecan or avelumab in RAS/BRAF wild-type ctDNA metastatic colorectal cancer patients represents a promising therapy.
The strategy of rechallenge is based on the idea that a particular group of patients with metastatic colorectal cancer (mCRC) who have not mutated RAS genes could still benefit from epidermal growth factor receptor (EGFR) inhibitors, even after they have progressed to an anti-EGFR-based therapy. Researchers conducted a combined analysis of two-phases II clinical trials to examine the effectiveness of rechallenge therapy in third-line mCRC patients with RAS/BRAF WT baseline circulating tumor DNA (ctDNA).
The study gathered individual data from 33 and 13 patients from the CAVE and CRICKET trials, respectively, who received cetuximab rechallenge as their third-line therapy. We calculated the overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and stable disease (SD) >6 months and reported any adverse events. The median PFS (mPFS) for the entire patient population of 46 was 3.9 months (95% Confidence Interval, CI 3.0-4.9), with a median OS (mOS) of 16.9 months (95% CI 11.7-22.1). The mPFS for CRICKET patients was 3.9 months (95% CI 1.7-6.2); with an mOS of 13.1 months (95% CI 7.3-18.9), and OS rates at 12, 18, and 24 months of 62%, 23%, and 0%, respectively. For CAVE patients, the mPFS was 4.1 months (95% CI 3.0-5.2), with an mOS of 18.6 months (95% CI 11.7-25.4), and OS rates at 12, 18, and 24 months of 61%, 52%, and 21%, respectively. Skin rash was recorded more frequently in the CAVE study (87.9% vs. 30.8%; p = 0.001), whereas the CRICKET trial saw a higher frequency of hematological toxicity (53.8%% vs. 12.1%; p = 0.003). The study suggested that third-line cetuximab rechallenge therapy in combination with either irinotecan or avelumab for RAS/BRAF WT ctDNA mCRC patients is a promising therapeutic option.
Source: https://pubmed.ncbi.nlm.nih.gov/36880426/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT04561336
Martini G, Ciardiello D, Famiglietti V, Rossini D, Antoniotti C, Troiani T, Napolitano S, Esposito L, Latiano TP, Maiello E, Del Re M, Lonardi S, Aprile G, Santini D, Masi G, Avallone A, Normanno N, Pietrantonio F, Pinto C, Ciardiello F, Cremolini C, Martinelli E. Cetuximab as third-line rechallenge plus either irinotecan or avelumab is an effective treatment in metastatic colorectal cancer patients with baseline plasma RAS/BRAF wild-type circulating tumor DNA: Individual patient data pooled analysis of CRICKET and CAVE trials. Cancer Med. 2023 Apr;12(8):9392-9400. doi: 10.1002/cam4.5699. Epub 2023 Mar 7. PMID: 36880426.
