KEY TAKEAWAYS
- The phase 2 study aimed to investigate the efficacy of Lenvatinib + Pembrolizumab in addressing the challenge of ICI resistance in MSS mCRC.
- Researchers observed potential benefits in specific PTS populations for the Lenvatinib and Pembrolizumab regimen as salvage therapy for MSS colorectal cancer; additional information will be provided later.
Colorectal cancer (CRC) ranks as the third most frequently diagnosed cancer globally, with over 1.9 million new cases reported in 2020. Despite the recognized modest activity of immune-checkpoint inhibitors (ICI) in microsatellite stable (MSS) metastatic colorectal cancer (mCRC) patients with a proficient mismatch repair system (pMMR), challenges persist. Despite T cell infiltration in MSS tumors, anti-PD-1 monoclonal antibodies prove ineffective due to the tumors’ lack of ICI expression, facilitating escape from immunosurveillance by mechanisms such as downregulating HLA expression.
A hypothesis emerges, suggesting that a specific subset of non-hypermutated MSS tumors may theoretically respond to PD-1/PD-L1 blockade therapy. While trials have indicated benefits from intensive combination chemotherapy with ICI for MSS tumors, such regimens are often unsuitable for fragile and older patients. Hence, exploring treatment options with lower toxicity becomes imperative for specific groups of patients with MSS tumors.
Zayana Sangadzhieva and her team aimed to focus on assessing the efficacy of Lenvatinib and Pembrolizumab in MSS mCRC, specifically targeting patients who may benefit from a less toxic treatment approach. The study estimated the survival distribution and response rate (RR) by employing the Kaplan-Meier method.
From this analysis, a cohort of 20 cases (male: 13, female: 7) with a median average age of 63 (32-75) years old revealed a median progression-free survival (PFS) of 4.5 months (95%CI: 1.4-14) and an overall survival (OS) of 10 months (95%CI: 2.5-26.4). RR was observed at 16%, while the disease control rate (DCR) stood at 25.6%. Notably, Grade 2 or more severe diarrhea emerged as an independent prognostic factor for both PFS (P = 0.004) and OS (P< 0.0001). Common treatment-related adverse events (TRAEs) included gastrointestinal toxicity and hepatic dysfunction, which, though present, did not reach severe levels, and no treatment-related deaths were observed.
The study concluded that, despite the ineffectiveness of LEAP-017, certain patient populations may benefit from this regimen as salvage therapy for MSS CRC. Additionally, the findings suggested that Grade 2 or more severe diarrhea holds the potential to serve as a predictive factor. In conclusion, further investigations in this field are deemed necessary to enhance understanding and refine therapeutic approaches for MSS CRC.
The study is sponsored by Merck Sharp & Dohme LLC.
Source: https://cslide.ctimeetingtech.com/immuno23hybrid/attendee/confcal/show/session/34
Clinical Trial: https://clinicaltrials.gov/study/NCT03797326
Sangadzhieva Z, et al. (2023).”ICI for patients with MSS metastatic colorectal cancer.” Presented at ESMO IO 2023 (Abstract 97P)
