Marwan Fakih, MD
Several key findings in metastatic colorectal cancer (mCRC) presented at the 2019 Gastrointestinal Cancers Symposium underscored the importance of understanding tumor biology, explained Marwan Fakih, MD.
For example, data from a randomized phase II study demonstrated a prolongation in median overall survival (OS) with the combination of durvalumab (Imfinzi) and tremelimumab plus best supportive care versus supportive care alone in patients with advanced refractory CRC. According to results from the Canadian Cancer Clinical Trials Group CO.26 trial, the immunotherapy regimen resulted in a median OS of 6.6 months when added to best supportive care versus 4.1 months with supportive care alone (HR, 0.72; 90% CI, 0.54-0.97; P
Although results were modest, they suggest that immunotherapy may have a role outside of patients with microsatellite instability–high (MSI-H) tumors, for whom pembrolizumab (Keytruda) is currently indicated after progression on prior therapy.
Moreover, the combination of encorafenib (Braftovi), binimetinib (Mektovi), and cetuximab (Erbitux) led to an unprecedented improvement in progression-free survival (PFS) and OS in patients with BRAF
V600E–mutant mCRC, according to results from the phase III BEACON trial. At a median follow-up of 18.2 months, results indicated a median PFS and OS of 8.0 months and 15.3 months, respectively, with the triplet regimen.2
“The biggest trend in CRC is understanding tumor biology, which is something that is happening across solid tumors,” said Fakih, professor, Department of Medical Oncology and Therapeutics Research, associate director for Clinical Investigations, Comprehensive Cancer Center, medical director, Judy and Bernard Briskin Center for Clinical Research, "We know that the better we understand the biology of the cancer, the better we can characterize CRC and fit our patients with the appropriate treatments.”
In an interview during the 2019 OncLive®
State of the Science Summit™ on Gastrointestinal Malignancies, Fakih, who is also co-director, Gastrointestinal Cancer Program, and section head, Gastrointestinal Medical Oncology, City of Hope, discussed these trials and highlighted other ongoing research in the field.
OncLive: What were some of the biggest updates from the 2019 Gastrointestinal Cancers Symposium?
: There are 2 main presentations that are important in the research and clinical practice setting of colon cancer. The first study looked at the role of immunotherapy in patients who had progressed on systemic chemotherapy. In this particular phase II trial, patients were randomized to receive a combination of durvalumab and tremelimumab [plus best supportive care] or best supportive care alone. Although we did not see any major responses or significant improvement in PFS in the immunotherapy arm, there was a significant trend in improvement in OS in patients who received the combination. Granted, the improvement was not that clinically significant.
This tells us that patients with mCRC, including those with microsatellite stable (MSS) colon cancer, may have the potential to respond to immunotherapy; this means that CRC is not necessarily a very cold tumor. There may be other strategies that can be investigated to further evaluate immunotherapy and add on to the findings that have been described.