Patients with colorectal cancer had high response rates with a modified triplet regimen of fluorouracil (Fluoroplex)/folinic acid, oxaliplatin (Eloxatin), and irinotecan (FOLFOXIRI) plus panitumumab (Vectibix) compared with FOLFOXIRI alone. Recently published in the Journal of Clinical Oncology, the phase II VOLFI trial data1 also show that the high response rates meant more patients who received panitumumab were able to undergo surgery.
The VOLFI trial enrolled 105 patients with RAS wild-type metastatic colorectal cancer who were randomly assigned in a 2 to 1 fashion to receive modified FOLFOXIRI plus panitumumab or FOLFOXIRI alone. In all, 63 patients received modified FOLFOXIRI plus panitumumab and 33 received FOLFOXIRI alone. The panitumumab regimen would be considered active if the panitumumab arm achieved an overall response rate (ORR) of 75% or higher.
Ultimately, the panitumumab arm achieved an ORR higher than 75%. In fact, 87.3% of patients who received modified FOLFOXIRI plus panitumumab had a response compared with 60.6% of patients who received FOLFOXIRI alone (odds ratio [OR]=4.469; 95% CI, 1.61 - 12.38), and the difference was statistically significant (P = .004). All the responses were partial responses except for two in the FOLFOXIRI arm, which were complete responses (CRs).
When asked for his perspective on the low CR rate, Brandon Smaglo, MD, assistant professor of internal medicine at the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine, who was not involved in the trial, toldCancerNetwork ® that he wouldn’t expect many CRs for this patient population.
“I’m totally fine if these tumors just shrink a little bit, because oftentimes, what you're trying to achieve in this setting is not a CR,” he explained. “What you’re trying to achieve is a very specific response that would somehow improve the outcome of surgery.”
In fact, the rate of secondary resection of metastases was higher among patients who received modified FOLFOXIRI plus panitumumab compared with patients who received FOLFOXIRI alone (33% vs 12%; OR=3.63; 95% CI, 1.13 - 11.67), and this difference was statistically significant (P = .02). In addition, the relapse-free survival after the first resection was nearly 4 months longer for the patients who received modified FOLFOXIRI plus panitumumab compared with patients who received FOLFOXIRI alone (7.9 vs 4.0 months; HR=0.62; 95% CI, 0.13 - 3.11), but this gain was not statistically significant (P = .56).
As for the safety profile, the frequency of grade 3 or 4 adverse events was higher for the panitumumab arm compared with the FOLFOXIRI arm (81.3% vs 66.7%). The most common grade 3 or 4 adverse events for the panitumumab arm were diarrhea (25%), neutropenia (15.6%), and dermatitis acneiform (14.1%). The most common grade 3 or 4 adverse events for the FOLFOXIRI arm were neutropenia (21.2%), diarrhea (12.1%), and peripheral neuropathy (12.1%).
Smaglo commented that the side effects were in line with what one would expect with a drug like panitumumab.
“[Panitumumab] has been around for long enough now that I think most of us are pretty comfortable with what to expect and how to manage it,” he said. “This isn’t something that we're putting patients on as an open-ended, indefinite treatment. It’s to be aggressive for a short period of time.”
One of the advantages of panitumumab, Smaglo said, is that although panitumumab side effects are not “totally tolerable,” they generally don’t overlap with chemotherapy.
Smaglo pointed out that these findings only apply to patients with RAS wild-type colorectal tumors, and while a “sizeable percentage”—between 40% to 60% —of colorectal tumors fit this criteria, panitumumab is “a little bit limited” in the sense that not everybody can get it.
Modest MD, D., et al. (2019). FOLFOXIRI Plus Panitumumab As First-Line Treatment of RAS Wild-Type Metastatic Colorectal Cancer: The Randomized, Open-Label, Phase II VOLFI Study (AIO KRK0109) | Journal of Clinical Oncology. [online] Ascopubs.org. Available at: https://ascopubs.org/doi/abs/10.1200/JCO.19.01340 [Accessed 23 Oct. 2019].