POCHI trial: combining pembrolizumab with standard therapy is effective in patients with pMMR/MSS mCRC and high tumor lymphocyte infiltration
Even though immune checkpoint inhibitors are generally considered to be ineffective in the treatment of microsatellite stable metastatic colorectal cancer (pMMR/MSS mCRC), approximately 15% of patients shows high levels of tumor infiltrating lymphocytes, and may therefore be sensitive to immune checkpoint inhibitors.1 In the POCHI study patients with unresectable pMMR/MSS mCRC and high tumor lymphocyte infiltration received first-line treatment with the immune checkpoint inhibitor pembrolizumab plus standard therapy. The preliminary results were presented by prof. David Tougeron during ESMO WCGIC.2
Study Design
The multicenter, single-arm, phase II study POCHI included patients with unresectable pMMR/MSS mCRC and high tumor lymphocyte infiltration. Participants were treated in the first line with pembrolizumab (200 mg, Q3W) plus CAPOX (oxaliplatin plus capecitabine: standard dose, Q3W) and bevacizumab (7.5 mg/kg, Q3W). High tumor lymphocyte infiltration was defined as having at least one positive immune score on a primary tumor resection specimen, either by TuLIS or Immunoscore© measurement. The primary endpoint was the progression-free survival (PFS). Key secondary endpoints were the overall survival (OS), the disease control rate (DCR), duration of response (DOR) and safety of the treatment regimen.
Results
A total of 182 patients were screened, of whom 28 (15%; median 66 years old, 61% male) had at least one positive immune score and were eligible for study participation. After a median follow-up of 19 months, 46% of the patients were still on treatment. At 12 months, the PFS was 68%. After 24 months the OS was 67%. A complete response was achieved by 21% of patients, while a partial response was seen for 54%. 21% of patients displayed stable disease and disease progression was observed in 4% of the study participants, which results in a DCR of 96%. The median DOR was 10 months. No deaths were reported that could be attributed to toxicity of the treatment, but 64% of patients experienced at least one grade 3 or 4 treatment related adverse event.
Conclusions
In conclusion, the preliminary results of the phase II POCHI trial shows that a first-line treatment consisting of a combination of pembrolizumab, CAPOX and bevacizumab is effective and has an acceptable safety profile in patients with unresectable pMMR/MSS mCRC and high tumor lymphocyte infiltration. If the final results of the POCHI trial are consistent with those presented, a larger randomized phase III study seems justified.
References
1. Allard M, et al. Linear quantification of lymphoid infiltration of the tumor margin: a reproducible method, developed with colorectal cancer tissues, for assessing a highly variable prognostic factor. Diagn Pathol 2012;156:
2. Tougeron D, et al. Pembrolizumab in combination with xelox and bevacizumab in patients with microsatellite stable (pMMR/MSS) metastatic colorectal cancer (mCRC) and a high immune infiltrate: A proof of concept study - Preliminary results of FFCD 1703 POCHI trial. Presented at ESMO WCGIC 2024; Abstract LBA1.
