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Safety and efficacy of nivolumab, an anti-PD1 immunotherapy, in patients with advanced basal cell carcinoma, after failure or intolerance to sonic Hedgehog inhibitors: UNICANCER AcSé NIVOLUMAB trial

Published:November 03, 2022DOI:https://doi.org/10.1016/j.ejca.2022.09.013

      Highlights

      • Local treatments and even SHH inhibitors can be insufficient to treat advanced BCC.
      • We evaluate Nivolumab in monotherapy for advanced BCC as an alternative.
      • Nivolumab seem to be a relevant option when there is no other treatment available.

      Abstract

      Background

      Basal cell carcinoma (BCC) is the most common human malignancy. In most cases, BCC has slow progression and can be definitively cured by surgery or radiotherapy. However, in rare cases, it can become locally advanced or, even more rarely, metastatic. The alternative recommended treatments are Sonic Hedgehog pathway inhibitors; however, the response is often short-lived.

      Methods

      This was a phase 2 basket study (NCT03012581) evaluating the efficacy and safety of nivolumab in a cohort of 32 advanced BCC patients, enrolled after failure of Sonic Hedgehog inhibitors, including 29 laBCC (91%) and 3 mBCC (9%).

      Results

      Compared to previously published studies, our population consisted of severe patients with a poor prognosis because they had already received multiple lines of treatment: all patients received previous Sonic Hedgehog inhibitors, 53% of patients already had chemotherapy and 75% radiotherapy. At 12 weeks, we reported 3.1% of complete responses, 18.8% of partial responses, and 43.8% of stable diseases. The best response rate to nivolumab reached 12.5% of complete responses (four patients), 18.8% of partial responses (three patients), and 43.8% of stable diseases (14 patients). Adverse events (AE) were mostly grade 2 or 3, slightly different to the adverse events observed in the treatment of metastatic melanoma (higher rate of diabetes, no thyroid dysfunction).

      Conclusion

      Nivolumab is a relevant therapeutic option for patients with advanced relapsing/refractory BCC.

      Keywords

      Abbreviations:

      AE (adverse event), BCC (basal cell carcinoma), CR (complete response), ECOG (Eastern Cooperative Oncology Group (Performans Status)), EMA (European Medicines Agency), FDA (Food and Drug Administration), ITT (intent-to-treat), laBCC (locally advanced BCC), mBCC (metastatic BCC), NCI CTCAE v4 (National Cancer Institute Common Terminology Criteria for Adverse Event version 4), ORR (objective response rate), OS (overall survival), PDL1 (programmed death ligand 1), PFS (progression-free survival), PR (partial response), RECIST (Response Evaluation Criteria In Solid Tumors), SHH (sonic Hedgehog), TMB (tumour mutation burden)
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