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

Eur J Cancer. 2022 Dec:177:103-111. doi: 10.1016/j.ejca.2022.09.013. Epub 2022 Oct 11.

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: Basal cell carcinoma; Cancer; Immune checkpoint; Immunotherapy; Locally advanced basal cell carcinoma; Metastatic basal cell carcinoma; Nivolumab; PD1 blocker.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / therapeutic use
  • Carcinoma, Basal Cell* / pathology
  • Hedgehog Proteins / metabolism
  • Hedgehog Proteins / therapeutic use
  • Humans
  • Immunotherapy
  • Neoplasm Recurrence, Local / drug therapy
  • Nivolumab / therapeutic use
  • Skin Neoplasms* / pathology

Substances

  • Antineoplastic Agents
  • Hedgehog Proteins
  • Nivolumab