![]() Are you excited about any other investigational combination regimens under exploration for MSI-H tumors? ![]() This is similar to an approach that is being utilized in the lung cancer field. Do they have lower tumor mutational burden? Do they have RAS mutations? Do they express other features that we have not yet identified? Those patients might actually benefit from pembrolizumab chemotherapy, at least initially. We need future studies that will identify the patients who will not benefit from pembrolizumab. What questions have been left with this research? This trial also showed a higher rate of patients having disease progression as best response on pembrolizumab this was about 29.4% compared with 12.3% chemotherapy. It then crosses over and provides a long-term PFS benefit. These curves cross at about 6.5 months, which means that, until that point, pembrolizumab is actually slightly detrimental. There appears to be a subgroup of patients who do better with chemotherapy initially, when compared with pembrolizumab. This was an interesting phenomenon that had a caveat: The curves actually crossed. The median PFS more than doubled, and there was a hazard ratio of 0.60. This trial involved about 300 patients and clearly showed that PFS, a coprimary end point with overall survival, was relevantly improved with the use of pembrolizumab over chemotherapy. However, once they’re identified, these patients have a great treatment option in the form of immunotherapy. These patients account for only 5% of with CRC. ![]() Grothey: The KEYNOTE-177 trial randomized patients with MSI-H or dMMR stage IV CRC to frontline pembrolizumab or investigator’s choice of standard -of-care chemotherapy. OncLive ®: What are the lessons from the KEYNOTE177 trial regarding the use of immunotherapy in patients with MSI-H disease? In an interview with OncLive ® during a 2020 Institutional Perspectives in Cancer webinar on gastrointestinal malignancies, Grothey, a medical oncologist and director of gastrointestinal cancer research at West Cancer Center and Research Institute, highlighted recent advancements in CRC treatment, including innovative combinations and emerging agents in the field. 5 “For me, this is the most exciting HER2targeted agent in CRC, as well as in other diseases, such as gastric cancer and breast cancer,” said Grothey. Lastly, the ADC fam-trastuzumab deruxtecan-nxki (Enhertu) has generated excitement, after having demonstrated a confirmed ORR of 45.3% (95% CI, 31.6%-59.6%) in patients with HER2-overexpressing unresectable and/or metastatic CRC, according to data from the DESTINY-CRC01 trial (NCT03384940). 4 “As such, right now, the FDA has endorsed encorafenib and cetuximab as a standard of care,” noted Grothey. However, data from the updated analysis revealed that the median OS was 9.3 months for both the triplet and the doublet. 3 The median OS was 9.0 months with the triplet, 8.4 months with the doublet, and 5.4 months with the control regimen the ORRs in these arms were 26%, 20%, and 2%, respectively. 2įor patients with BRAF V600E–mutant metastatic CRC, data from the phase 3 BEACON CRC trial (NCT02928224) showed that a regimen composed of encorafenib (Braftovi) and cetuximab (Erbitux) with or without binimetinib (Mektovi) improved overall survival (OS) and objective response rates (ORRs) compared with standard chemotherapy. Moreover, the PD-1 inhibitor reduced the risk for progression on next-line therapy by 37%. “We need to perform trials that will help us identify these patients.” An additional analysis presented during the 2021 Gastrointestinal Cancers Symposium demonstrated that patients treated with pembrolizumab experienced better health-related quality of life. 1 “However, we need to understand that there is a subgroup of patients who do not benefit from pembrolizumab, even though they express dMMR,” said Grothey. Ultimately, this is a new era of oncology, and we see more improvements each year.”īased on data from the phase 3 KEYNOTE-177 trial (NCT02563002), which showed that single-agent pembrolizumab (Keytruda) resulted in a doubling of progression-free survival (PFS) versus standard chemotherapy, the immunotherapy has become the new frontline standard for patients with microsatellite instability–high (MSI-H)/mismatch repair deficient (dMMR) metastatic CRC. “This can be done effectively with fewer toxicities, when compared with chemotherapy. We must embrace molecular profiling in all patients with gastrointestinal malignancies because we now have many drugs available that can target specific disease types,” said Grothey. “We are beyond the one-size-fits-all treatment approach for patients with CRC. With immunotherapy targeted combination regimens, and a novel antibody-drug conjugate (ADC), the colorectal cancer (CRC) paradigm is bursting with personalized options, according to Axel Grothey, MD.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |