Discussion
cancer typesThe, tumor, toxicity, toxicities, PD, hypotension, tumors
INFILTRATE, ACUTE KIDNEY FAILURE, TUMORS, TUMOR
The NICOL phase-I trial validated the recommended phase 2 dose of 240 mg q2w nivolumab combined with and following CRT for LACC patients. Indeed, although three DLT were observed, these toxicities corresponded to hypotension and acute kidney failure, which were unrelated to nivolumab but rather to cisplatin administration. The acute toxicity profile of this triple combination was similar to what is commonly observed with cisplatin CRT for LACCIn agreement with previously reported data in advanced melanomaThe synergy between angiogenesis targeting and immune checkpoint inhibition is under investigation in numerous cancer typesThe CALLA study—a phase-III, randomized trial (NCT03830866)Of note, nor tumor histology or HPV status were associated with an outcome of the combination of CRT and PD-1 inhibition in our study. In addition, PD-L1 expression on tumor cells per se did not enrich for response to PD-1 blockade, unlike it was reported in studies testing the efficacy of pembrolizumab in metastatic or unresectable cervical cancerRegarding the immunological correlates of clinical outcome, and in line with the transcriptomic data, we observed that PF patients display higher numbers of proliferating, Ki67With respect to intratumoral Tregs, although they have been often associated with poorer clinical outcomeIn line with the clinical outcome and with the immune infiltrate features, PD—unlike PF patients—displayed enhanced PD-1 expression in both peripheral CD4NiCOL is the first clinical trial to report on immune correlates of response to nivolumab with and following CRT in patients with LACC. Its limits are inherent to those of phase-I trials, in particular the limited number of patients, the absence of a comparator arm, the short follow-up, and the lack of paired pre- and on-treatment tumor biopsies. In particular, given the absence of a comparator arm, the biomarker data need to be interpreted with caution. Aware that further testing in randomized clinical trials is warranted, we propose that nivolumab with and following CRT may prove beneficial in LACC patients, whose tumors display a brisk, pretreatment immune infiltrate in the proximity of PD-L1