An updated analysis of safety and efficacy of oxaliplatin/bevacizumab ± panitumumab for first-line treatment of metastatic colorectal cancer from a randomized, controlled trial (PACCE)

Hecht and coauthors presented the results of a trial that evaluated the benefit of adding panitumumab (Vectibix, Amgen) to a first‐line FOLFOX (leucovorin, 5‐fluorouracil, oxaliplatin [Eloxatin, Sanofi‐Aventis]) regimen containing bevacizumab (Avastin, Genentech) in patients with metastatic colorectal cancer. In the previously reported PACCE trial, a total of 823 patients received bevacizumab plus FOLFOX alone (n=410) or with panitumumab (another arm administered bevacizumab plus an irinotecan‐based regimen with or without panitumumab). The findings reported at this symposium represent updated results from this arm of the trial, which was discontinued because addition of the fully human monoclonal antibody panitumumab did not improve progression‐free survival and was associated with significant toxicities. The patients, whose ECOG performance status was 0 or 1, were randomized to receive either panitumumab 6 mg/kg every 2 weeks or no panitumumab concomitant with bevacizumab plus FOLFOX until disease progression or intolerability. The primary objective was to assess progression‐free survival, and tumor assessments were performed every 12 weeks. At the data cutoff on May 31, 2007, 94% of patients had completed first‐line treatment, with a median follow‐up of 12.2 months (range, 0‐26.3 months). The median progression‐free survival was 9.5 versus 11 months (95% CI, 8.7‐10.9 vs 10.3‐11.9) for patients who did and did not receive panitumumab, respectively. The median time to treatment failure was 5.7 versus 5.9 months (95% CI, 5.5‐6.0 vs 5.7‐6.2) for patients who did and did not receive panitumumab, respectively. No patients who received panitumumab achieved complete response, and 186 patients each achieved partial response. Grade 3/4 adverse events were significantly worse among patients who received panitumumab and included diarrhea (24% vs 13%), infections (19% vs 10%), dehydration (18% vs 6%), skin toxicity (39% vs 2%), hypokalemia (10% vs 4%), and pulmonary embolism (6% vs 4%). Grade 5 adverse events were infections (1% vs 1%) and pulmonary embolism (1% vs 0%). There were 140 (36%) death events reported among patients who received panitumumab as compared to 107 (26%) in the cohort who did not receive panitumumab. The authors reported that, in exploratory analyses, patients with worse ECOG status and elderly age (>80 years) who received panitumumab appeared to experience worse outcomes. Overall, panitumumab plus FOLFOX with bevacizumab was associated with shorter progression‐free survival and increased toxicity. This combination is thus considered unsuitable in the general population of patients with metastatic colorectal cancer. Further data collection and analyses are ongoing.