As a leading cause of cancer death worldwide, colorectal cancer (CRC) is the third most-common cancer globally. The mismatch repair of microsatellite-instability- high (MSI-H) pathway, a major driver of this tumor type, can be found in around 15% of cases. This discovery has not only provided precious insights into the diversity of CRC, but also calls for a more personalized approach for the optimal treatment of these patients.
Building on the interim analysis of the phase III KEYNOTE-177 trial, showing that pembrolizumab as monotherapy without chemotherapy is both more effective and less toxic as first-line treatment for patients with MSI-H or mismatch repair–deficient (dMMR) CRC, latest data from this study reported in The New England Journal of Medicine* not only represents important progress in biomarker-driven approaches to more effectively target this disease, but also highlights the promise of immunotherapy in this patient population.
Reflective of the relevance of this potentially practice-changing trial, Nature Reviews Clinical Oncology has recently published a Research Highlight** covering KEYNOTE-177, and invited our Director, Josep Tabernero -who was not involved in this trial- to briefly underline why these findings could be important for patients with CRC.
Commenting for VHIO’s Global Communications, Josep Tabernero observed, “Latest findings comparing the efficacy of PD-1 blockade with chemotherapy as first-line therapy for dMMR/MSI-H CRC, show that pembrolizumab significantly extends longer progression-free survival than chemotherapy. As importantly, fewer treatment-related adverse events were observed.”
He added, “KEYNOTE-177 demonstrates the value of MSI-H status in more precisely guiding the treatment of our patients and supports how a deeper understanding of the molecular makeup of these tumors are enabling researchers to advance personalized medicine as well develop novel, more potent therapeutic strategies against metastatic CRC.”
Mounting evidence from this potentially practice-changing trial, which was co-authored by Elena Élez, Clinical Investigator of VHIO’s Gastrointestinal and Endocrine Tumors Group, and a Medical Oncologist at the Vall d’Hebron University Hospital’s Medical Oncology Department, points to a change in the current treatment paradigm by significantly improving outcomes for patients suffering from this disease.
*André, T. et al. Pembrolizumab in microsatellite-instability–high advanced colorectal cancer. N. Engl. J. Med. 383, 2207–2218 (2020).
**Romero, D. New first-line therapy for dMMR/MSI-H CRC. Nat Rev Clin Oncol (2020). https://doi.org/10.1038/s41571-020-00464-y.