Richard Kim, MD, on Future Research Efforts With Immunotherapy Combos in Metastatic CRC

During the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, Richard Kim, MD, service chief of Medical Gastrointestinal Oncology and senior member in the Gastrointestinal Oncology Department at Moffitt Cancer Center in Tampa, Florida, sat down with CancerNetwork® to discuss future research efforts assessing immunotherapy combinations in metastatic colorectal cancer.

Following the results of the phase 1b KEYNOTE-651 trial (NCT03374254)—which examined the use of pembrolizumab (Keytruda) plus modified oxaliplatin, leucovorin, and fluorouracil (5-FU; FOLFOX7) or irinotecan, leucovorin, and 5-FU (FOLFIRI) in metastatic colorectal cancer—Kim stated that future research will need to focus on biomarkers to better identify the best candidates for treatment.

Transcript:

The KEYNOTE-651 study [used a] combination of chemotherapy plus immunotherapy plus a MEK inhibitor. But there [have been] other studies that have been presented and published after using chemotherapy plus immunotherapy plus a targeted therapy in the first-line setting. One was a trial called the [phase 2] AtezoTRIBE study [NCT03721653]2 and the second one was the phase 2/3 CheckMate 9X8 trial [NCT03414983] that was presented this year at the Genitourinary Cancers Symposium;3 it’s a very similar concept. They’re using chemotherapy. In the AtezoTRIBE study, it was FOLFOXIRI plus bevacizumab [Avastin] plus atezolizumab [Tecentriq] vs standard treatment of FOLFOXIRI plus bevacizumab. The CheckMate study was using FOLFOX6 plus nivolumab plus bevacizumab vs standard FOLFOX plus bevacizumab. In the CheckMate 9X8 study, the primary end point of PFS [progression-free survival] was negative; there was no difference in PFS, unfortunately. In the AtezoTRIBE study, there was a slight improvement in PFS, however about 6% to 7% of the patient population were MSI [microsatellite instability]–high. If you exclude those patients [who were] MSI high, then the PFS became almost equal.

Based on those 2 studies that added a targeted therapy on top of chemotherapy and immunotherapy, I think our enthusiasm has dampened to some degree. Therefore, based on the data, it is really unclear whether adding pembrolizumab to targeted therapy and chemotherapy in MSS colon cancer is really synergistic. The next step is really to try to look at this patient population to come up with a better [predictive] biomarkers to see which patients do benefit from immunotherapy. That’s our task moving forward.

References

1. Kim RD, Tehfe M, Kavan P, et al. Pembrolizumab (pembro) plus mFOLFOX7 or FOLFIRI for metastatic colorectal cancer (CRC) in KEYNOTE-651: Long-term follow-up of cohorts B and D. J Clin Oncol. 2022;40(suppl 16):3521. doi:10.1200/JCO.2022.40.16_suppl.3521
2. Antoniotti C, Borelli B, Rossini D, et al. AtezoTRIBE: a randomised phase II study of FOLFOXIRI plus bevacizumab alone or in combination with atezolizumab as initial therapy for patients with unresectable metastatic colorectal cancer. BMC Cancer. 2020;20(1):683. doi:10.1186/s12885-020-07169-6
3. Lenz H, Parikh A, Spigel D, et al. Nivolumab (NIVO) + 5-fluorouracil/leucovorin/oxaliplatin (mFOLFOX6)/bevacizumab (BEV) versus mFOLFOX6/BEV for first-line (1L) treatment of metastatic colorectal cancer (mCRC): phase 2 results from CheckMate 9X8. J Clin Oncol. 2021;40(suppl 4):8. doi: 10.1200/JCO.2022.40.4_suppl.008