Chemoradiotherapy with concomitant nivolumab was found to be safe and effective for improving progression-free survival rates in cervical cancer.
Concurrent chemoradiotherapy (CRT) improves immune-mediated tumor control by increasing phagocytosis and antigen presentation. The NiCOL phase I trial, conducted by Rodrigues et al., aimed to determine the efficacy and safety profile of nivolumab and its dosage for the phase II clinical trial. The findings are published in the journal Nature Communications.
This study included a total of 16 patients, out of whom two were diagnosed with adenocarcinomas, and the remaining patients had squamous cell carcinomas. The prevalence of human papillomavirus (HPV) infection in the study sample was 87.5%, or 14 tumor cases. The remaining two HPV-negative cases were associated with squamous cell carcinoma.
Safety of Chemoradiotherapy and Concomitant Nivolumab
Of the 15 patients assessed for dose-limiting toxicity (DLT), two developed grade 3 hypotension, one suffered from acute kidney injury of grade 3, and three experienced DLT. Of the total number of patients, five suffered from acute grade 4 adverse events unrelated to DLT. Patients with acute grade 4 adverse events unrelated to DLT also experienced anemia, hypomagnesemia, neutropenia, lymphopenia, and hypokalemia.
After 11 weeks of DLT assessment, three further patients receiving maintenance nivolumab suffered from late grade ≥ 3 adverse events. There were no deaths, and no patients developed a second cancer. The recommended dose for the phase II trial was 240 mg q2w combined with CRT.
Efficacy of Chemoradiotherapy and Concomitant Nivolumab
While receiving CRT, none of the patients demonstrated disease progression. After completing brachytherapy, the overall response rate was 93.8%. Only one patient had disease progression, while of the remaining patients, eight had a complete response to treatment and seven had a partial response to treatment. The two HPV-negative tumor patients had a complete response. Three patients had loco-regional disease progression at follow-up, whereas one had logo-regional progression plus distant disease progression.
Biologic Differences in Progression-Free and Progressive Disease Subjects
The gene set enrichment and gene set variation analyses suggested that progression-free (PF) subjects had enrichment in interferon-alpha (IFN-α) and IFN-γ gene sets. On the contrary, progressive disease (PD) subjects demonstrated enrichment in KRAS signaling, angiogenesis, and epithelial-to-mesenchymal transition gene sets. Furthermore, PF patients had greater proximity between tumor cells and tumor-infiltrating T cells. In PD patients, expression of the immune checkpoint protein PD-1 was related to a less functional phenotype. The higher levels of circulating Ki67+ regulatory T cells in PD patients indicated an inefficient anti-tumor immune response.
Rodrigues, M., Vanoni, G., Loap, P., Dubot, C., Timperi, E., Minsat, M., Bazire, L., Durdux, C., Fourchotte, V., Laas, E., Pouget, N., Marret, G., Lesage, L., Meseure, D., Lecompte, L., Servant, N., Vacher, S., Bieche, I., Malhaire, C., . . . Romano, E. (2023). Nivolumab plus chemoradiotherapy in locally-advanced cervical cancer: The NICOL phase 1 trial. Nature Communications, 14(1), 1-15. https://doi.org/10.1038/s41467-023-39383-8