Intermittent vs Continuous Panitumumab Plus FOLFIRI for First-Line Treatment of Patients With RAS/BRAF Wild-Type Colorectal Cancer

Results from the Phase 2 IMPROVE Study

At the 2023 World Congress on Gastrointestinal Cancers in Barcelona, Spain, Alfonso De Stefano, MD, PhD, Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione Giovanni Pascale, IRCCS di Napoli, Naples, Italy, presents updated results from the randomized, non-comparative, multicenter, phase 2 IMPROVE study, which examines intermittent or continuous panitumumab combined with FOLFIRI for the first-line treatment of patients with RAS/BRAF wild-type metastatic colorectal cancer.

Dr Stefano et al concluded, “Updated analyses confirmed that intermittent FOLFIRI/PANI strategy produces a long [progression-free survival (PFS) on treatment (OT)] and a reduced skin severe and skin burden toxicity without any detrimental effect on [overall survival].”

Transcript:

I'm Alfonso De Stefano, I'm a medical oncologist at the Institute of Pascal from Naples, Italy. I presented the updated results of the IMPROVE trial, which is a phase 2 randomized non-comparative multicenter trial.

This trial randomized patients to a first-line for metastatic colorectal cancer, RAS and BRAF wild type. Patients were randomized to receive FOLFIRI panitumumab continuously in arm A, and in arm B, patients were randomized to receive intermittent [FOLFIRI and panitumumab] given for 4 months, [up to] 8 cycles.

The main point of the trial was the evaluation of progression-free survival on treatment. That was the time inter-occurring between randomization until documented progression on treatment. Moreover, among the secondary points, there was the evaluation of safety profile, response rate, and overall survival.

The updated results of this trial showed that skin toxicity was superior for patients that received anti-EGFR continuously if compared with those patients that received in the experimental arm, panitumumab intermittently. And the skin toxicity burden, that's the sum of all grades of toxicity reported by patients along all cycles of chemotherapy, was superior for the continuous arm.

Moreover, progression-free survival on treatment was superior for patients undergoing intermittent chemotherapy, with a difference of 7 months. And at the analysis, based on the primary tumor location, this evidence was even more evident. Moreover, we report also the results of overall survival (OS). In particular, any difference was [] between the intermittent and the continuous arm. [Note: In the updated results, OS was 31.0 months (95% confidence interval [CI], 24.7 to 37.2) in arm A and 32.2 months (95% CI, 23.6 to 40.8) in arm B.]

In this context, as conclusions of this trial, we report that the intermittent strategy with anti-EGFR reports a longer PFS on treatment. There [isn’t] any difference between the overall survival at times reported by the continuous arm and the intermittent strategy with the stop-and-go.

These results are very important for patients as treatment-only patients, after 4 months of treatment and the continuous toxic effect reported by anti-EGFR may be detrimental for the quality-of-life of patients. The IMPROVE trial is a phase 2 trial, so these preliminary results need to be confirmed, and in the next month we plan a phase 3 trial.

Source:

De Stefano A, Giuliani F, Nasti G, et al. Intermittent or continuous panitumumab plus FOLFIRI for first-line treatment of patients with RAS/BRAF wild-type metastatic colorectal cancer: An update of survival/toxicity and preliminary results of genomic alterations from IMPROVE study. Presented at the 2023 World Congress on Gastrointestinal Cancers; June 28-July 1, 2023; Barcelona, Spain. Abstract SO-26