Panitumumab plus trifluridine/tipiracil as anti‐<scp>EGFR</scp> rechallenge therapy in patients with refractory <scp><i>RAS</i></scp> wild‐type metastatic colorectal cancer: Overall survival and subgroup analysis of the randomized phase <scp>II VELO</scp> trial
Stefania Napolitano, Davide Ciardiello, Vincenzo De Falco, Giulia Martini, Erika Martinelli, Carminia Maria Della Corte, Lucia Esposito, Vincenzo Famiglietti, Alessandra Di Liello, Antonio Avallone, Claudia Cardone, Alfonso De Stefano, Vincenzo Montesarchio, Maria Giulia Zampino, Nicola Fazio, Massimo Di Maïo, Sara Del Tufo, Ferdinando De Vita, Lucia Altucci, Francesca Marrone, Fortunato Ciardiello, Teresa Troiani
Abstract
The randomized phase II VELO trial showed that the addition of panitumumab to trifluridine/tipiracil significantly improves progression-free survival (PFS) as compared to trifluridine/tipiracil in third-line therapy in patients with refractory RAS wild-type (WT) metastatic colorectal cancer (mCRC). With longer follow-up, final overall survival results and posttreatment subgroup analysis are presented. Sixty-two patients with refractory RAS WT mCRC were randomly assigned to receive, as third-line therapy, trifluridine/tipiracil alone (arm A) or in combination with panitumumab (arm B). Primary endpoint was PFS; secondary endpoints included overall survival (OS) and overall response rate (ORR). Median OS was 13.1 months (95% CI 9.5-16.7) in arm A compared to 11.6 months (95% CI 6.3-17.0) in arm B (HR: 0.96, 95% CI 0.54-1.71, P = .9). To evaluate the impact of subsequent lines of treatment, subgroup analysis was performed for the 24/30 patients in arm A, that received fourth-line therapy after disease progression. Median PFS was 4.1 months (95% CI 1.44-6.83) for 17 patients treated with anti-EGFR rechallenge as compared to 3.0 months (95% CI 1.61-4.31) for seven patients that received other therapies (HR: 0.29, 95% CI 0.10-0.85, P = .024). Median OS from the start of fourth-line treatment was 13.6 months (95% CI 7.2-20), and 5.1 months (95% CI 1.8-8.3) for patients treated with anti-EGFR rechallenge vs other therapies, respectively (HR: 0.30, 95% CI 0.11-0.81, P = .019). Final results of the VELO trial support the role of anti-EGFR rechallenge in the continuum of care of patients with RAS/BRAF WT mCRC.