Early immunotherapy shows higher response in advanced basal cell carcinoma

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 the course of 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 shrunk or disappeared after treatment. In this study, the ORR is significantly higher than published response rates of approximately 25%-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 tumor 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."

Govind Warrier, M.D., M.P.H., assistant professor of oncology at the Johns Hopkins Kimmel Cancer Center, Bloomberg~Kimmel Institute for Cancer Immunotherapy, and co-leader of the study

Investigators also explored whether adding relatlimab, an anti–LAG-3 immune checkpoint inhibitor, to nivolumab could induce tumor 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 from work at Johns Hopkins revealing that LAG-3 may be an important immune checkpoint in BCC. 

"We discovered that LAG-3 is commonly expressed in the tumor microenvironment of aggressive basal cell carcinomas, suggesting LAG-3 blockade could be an attractive therapeutic option for these patients," said Julie Stein Deutsch M.D., 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. 

Immune checkpoint inhibitors such as nivolumab and relatlimab work by blocking proteins that cancers use to evade the immune system, enabling the body's immune cells to recognize and destroy tumor cells. Nivolumab is FDA-approved for patients with melanoma and several other cancers. Relatlimab in combination with nivolumab is FDA-approved for melanoma and is being tested in patients with a variety of other cancer types. 

In the United States, approximately 10,000 patients each year develop inoperable BCC, according to a report in the Annals of Oncology. Current first-line treatment with hedgehog pathway inhibitors is often limited by short-lived responses and intolerable side effects. Response rates to second-line anti-PD-1 (about 20 – 30%) are low relative to response rates of other skin cancers to first-line anti-PD-1 (about 40 – 50%), the researchers say. 

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