Marinde J.G. Bond, PhD Candidate, on Colorectal Liver Metastases: FOLFOX/FOLFIRI, Bevacizumab, and Panitumumab
ESMO Congress 2022
Marinde J.G. Bond, PhD Candidate, of the University Medical Center, Utrecht, discusses phase III findings from the CAIRO5 study of the Dutch Colorectal Cancer Group, the first such trial in defined subgroups of patients with initially unresectable colorectal cancer liver metastases and left-sided and RAS/BRAF V600E wild-type tumor. The study compared FOLFOX/FOLFIRI plus either bevacizumab or panitumumab (Abstract LBA21).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
CAIRO5 is the first randomized controlled phase III trial in which the currently most effective systemic regimens were compared in defined subgroups of patients with initially unresectable colorectal cancer liver metastasis, as defined by a liver expert panel. Patients with RAS/BRAF-mutated and/or a right-sided primary tumor were randomized between dub chemotherapy and triplet chemotherapy, both plus bevacizumab. The results of this group were presented at ESCO annual meeting last June and patients with RAS/BRAF wild-type, and left-sided primary tumors were randomized between doublet chemotherapy and either bevacizumab or panitumumab. I presented the results of this group, which evaluated 230 patients.
A novel aspect of this study is the Liver Expert Panel, which evaluates unresectability at baseline, according to redefined criteria, and resectability every 2 months during follow up, the Liver Expert Panel consisted of 15 liver surgeons and three abdominal radiologists. The panel procedure was as follows. The CT scans were uploaded and reviewed by one abdominal radiologist and then by three liver surgeons. If no consensus among these three liver surgeons existed, then two additional surgeons were invited and the final decision was made by majority votes. Consensus on unresectability at baseline was present in 67% and during follow up in 42%.
Based on these results and the results of in-depth analysis, we can conclude that the use of a liver expert panel is feasible and allows the selection of an increased number of patients who are eligible for local treatments with curative intent. The primary endpoint was progression-free survival and the median progression-free survival in the bevacizumab of arm, 10.6 months, and in the panitumumab arm, 10.3 months. This was not significantly different, with a hazard ratio of 1.12 and the p-value of 0.44. Panitumumab was associated with more grade 3 or higher toxicity, which mainly consisted of skin toxicity and diarrhea. Panitumumab significantly increased response rate and depth of response, which, however, did not translate into an increased local treatment rate of liver metastasis.
In conclusion, the median progression free survival was not different between the use of either bevacizumab or panitumumab to FOLFOX or FOLFIRI. The local treatment rate was not significantly different either despite the higher response rate and higher depth of response. Considering the results of previous anti-EGFR trials, the data and overall survival should be weighted before we can draw a final conclusion about the use of anti-EEGR therapy in patients with initially unresectable colorectal cancer liver metastasis and their-left sided and RAS/BRAF wild-type tumor.
Toni K. Choueiri, MD, of the Dana-Farber Cancer Institute, and Laurence Albiges, MD, PhD, of France’s Gustave Roussy Cancer Centre, discuss phase III findings showing that cabozantinib in combination with nivolumab and ipilimumab reduced the risk of disease progression or death compared with the combination of nivolumab plus ipilimumab in patients with previously untreated advanced renal cell carcinoma of IMDC (the International Metastatic RCC Database Consortium) intermediate or poor risk. However, the combination of cabozantinib, nivolumab, and ipilimumab vs nivolumab plus ipilimumab did not demonstrate an overall survival benefit to patients (Abstract LBA8).
Bernd Kasper, MD, PhD, of Germany’s Mannheim Cancer Center, discusses phase III data from the DeFi trial, the largest study conducted to date for patients with desmoid tumors. The trial showed that the gamma secretase inhibitor nirogacestat demonstrated improvements in all primary and secondary efficacy endpoints. Although considered benign because of their inability to metastasize, desmoid tumors can cause significant morbidity and, occasionally, mortality in patients (Abstract LBA2).
Laurence Buisseret, MD, PhD, of Belgium’s Institut Jules Bordet, discusses phase II results from the SYNERGY trial, which tested first-line chemoimmunotherapy of durvalumab, paclitaxel, and carboplatin with or without the anti-CD73 antibody oleclumab in patients with advanced or metastatic triple-negative breast cancer. Although adding oleclumab to durvalumab with chemoimmunotherapy did not increase the clinical benefit rate at week 24, research is ongoing to better understand the mechanisms of response and resistance to this study combination (Abstract LBA17).
Axel Bex, MD, PhD, of the Netherlands Cancer Institute, discusses phase III findings from the IMmotion010 study, which evaluated the efficacy and safety of atezolizumab vs placebo in patients with renal cell cancer who are at high risk of disease recurrence following nephrectomy (Abstract LBA66).
John B.A.G. Haanen, MD, PhD, of The Netherlands Cancer Institute, discusses recent phase III findings, which show that tumor-infiltrating lymphocytes (TILs) improve progression-free survival compared with ipilimumab by 50% in patients with advanced melanoma after not responding to anti–PD-1 treatment. Around 50% of TIL-treated patients had a response, and 20% had a complete response (Abstract LBA3).