Earlier immunotherapy benefits BCC patients

Durable, ongoing near-complete response to nivolimab + relatlimab in a 64-year-old with locally-advanced BCC after resistance to 26 weeks of nivolimab alone. Photo by: Evan Lipson, M.D.

A new study led by researchers at the Johns Hopkins Kimmel Cancer Center found that patients with advanced basal cell carcinoma (BCC) may benefit from receiving immunotherapy earlier in treatment.

Results from the phase 2 clinical trial (NCT03521830), presented Oct. 20 at the European Society for Medical Oncology (ESMO) annual meeting, show that first-line nivolumab, a PD-1 immune checkpoint inhibitor, produced an objective response rate (ORR) of 52% in 29 patients with inoperable BCC. Objective response rate is the percentage of patients in the study whose cancer shrank or disappeared after treatment. In this study, the ORR is significantly higher than published response rates of approximately 25% to 30% for second-line anti-PD-1 administered after a hedgehog pathway inhibitor, the current standard of care, the researchers report.

“Our results show that we can improve the likelihood of tumour response in patients with advanced basal cell carcinoma by administering anti-PD-1 in the front line, rather than after hedgehog pathway inhibitors. We look forward to further investigating these findings in larger, randomized trials,” said the study’s co-leader, Govind Warrier, MD, MPH, in a press release.

Dr. Warrier is an assistant professor of oncology at the Johns Hopkins Kimmel Cancer Center, Bloomberg-Kimmel Institute for Cancer Immunotherapy.

Investigators also explored whether adding relatlimab, an anti–LAG-3 immune checkpoint inhibitor, to nivolumab could induce tumour regressions in patients whose disease had progressed on nivolumab alone. Among 13 such patients, the ORR was 31% (4 of 13). The rationale for testing this combination was based on promising results in melanoma studies, where adding anti-LAG-3 to anti-PD-1 helped overcome resistance to single-agent anti-PD-1, and on work at Johns Hopkins, which revealed that LAG-3 may be an important immune checkpoint in BCC.

“We discovered that LAG-3 is commonly expressed in the tumour microenvironment of aggressive basal cell carcinomas, suggesting LAG-3 blockade could be an attractive therapeutic option for these patients,” said Julie Stein Deutsch, MD, assistant professor of dermatology, pathology, and oncology at the Johns Hopkins University School of Medicine, member of the Bloomberg-Kimmel Institute for Cancer Immunotherapy, and a co-leader of the study. LAG-3 was first co-characterized by scientists at the Bloomberg-Kimmel Institute for Cancer Immunotherapy.

In the United States, approximately 10,000 patients each year develop inoperable BCC, according to a report in the Annals of Oncology. Short-lived responses and intolerable side effects often limit the efficacy of current first-line hedgehog pathway inhibitor therapy. Response rates to second-line anti-PD-1 (about 20 to 30%) are low relative to response rates of other skin cancers to first-line anti-PD-1 (about 40 to 50%), the researchers say.

“These findings highlight important opportunities to improve outcomes for patients with advanced BCC, a population with few effective treatments,” Dr. Warrier said.