Cemiplimab, a programmed cell death protein 1 (PD-1) inhibitor, was approved in 2021 as the first and only systemic therapy to demonstrate clinical benefit among patients with advanced basal cell carcinoma (BCC) previously treated with hedgehog pathway inhibitor (HHI) therapy. At the American Association for Cancer Research (AACR) Annual Meeting in April, Dr. Karl Lewis, Professor in the Division of Medical Oncology at the University of Colorado, presented the primary results of the EMPOWER-BCC 1 trial of cemiplimab for patients with metastatic BCC. In this interview, Dr. Lewis delves further into the efficacy and safety data he presented and explains its significance for patients with this difficult-to-treat disease.
Oncology Data Advisor: What are some of the most challenging aspects of treating and managing patients with metastatic BCC?
Karl Lewis, MD: Metastatic BCC can be quite challenging to treat, given the extent of the cancer. Surgery and radiation are usually no longer an option, so patients may then receive a class of medicines called HHIs. While effective for some, many patients may discontinue HHI therapy due to progressive disease or intolerance to adverse events and will require another treatment. Until the approval of cemiplimab, there were no other options after HHI therapy.
Oncology Data Advisor: Can you comment on the significance of the recently presented data on cemiplimab-rwlc for patients with metastatic BCC who have progressed on or are intolerant of HHIs?
Dr. Lewis: This research is a continuation of the EMPOWER-BCC 1 study, which formed the basis of the FDA approval of cemiplimab-rwlc in February 2021 as the first and only immunotherapy treatment to show a clinical benefit in patients with metastatic disease following HHI therapy, or for whom an HHI is not appropriate in a pivotal trial. Cemiplimab-rwlc was granted accelerated approval by the FDA in the metastatic BCC indication based on an interim analysis showing the impact of treatment with cemiplimab on tumor response rate and durability of response. Full approval for this indication may be contingent upon verification and description of clinical benefit.
The EMPOWER-BCC 1 study included 54 patients with metastatic BCC who received treatment with cemiplimab 350 mg intravenously every 3 weeks for up to 93 weeks or until disease progression occurred, following HHI treatment. Results demonstrated that cemiplimab provided clinically meaningful antitumor activity, including durable responses, in this patient population. Specifically, the confirmed overall response rate per independent central review (ICR) was 24.1% (95% confidence interval [CI]: 13.5-37.6), with 1 complete response and 12 partial responses.
Among responders, the median time to response was 4.0 months (range: 2.0−10.5) per independent central review (ICR). The estimated median duration of response per ICR was 16.7 months (95% CI: 9.8–not evaluable [NE]). Median overall survival was not reached (95% CI: 25.7-NE), but the 12-month Kaplan-Meier estimation of overall survival was 84.4% (95% CI, 71.3-91.9). Median Kaplan-Meier progression-free survival was 8.3 months (95% CI: 4.2-15.9) per ICR.
The safety profile was generally consistent with that previously described for cemiplimab and other programmed cell death protein 1 (PD-1) inhibitors. Specifically, the most common treatment-emergent adverse events of any grade were fatigue (42.6%), diarrhea (37.0%), constipation (22.2%), and hypertension (20.4%). Immune-related adverse events of any grade occurred in 61.1% of patients. Grade ≥3 immune-related adverse events were seen in 9.3% of patients, with the only grade ≥3 immune-related adverse event occurring in more than one patient being colitis. Two patients (3.7%) had a serious treatment-emergent adverse event resulting in death, including one patient with staphylococcal pneumonia and one with hemoptysis.
These results complement those previously reported for the locally advanced BCC cohort, and together indicate that cemiplimab is highly active in advanced BCC tumors.
Oncology Data Advisor: What are some additional future directions in the treatment of patients with metastatic BCC?
Dr. Lewis: There are ongoing studies of combination immunotherapy in advanced BCC as well as novel targeted therapies against the hedgehog pathway. In addition, I would like to see some data in the future about the use of immunotherapy as a first-line treatment for patients with advanced BCC.
Oncology Data Advisor: Do you have any words of advice for members of the cancer care team who are using cemiplimab to treat their patients?
Dr. Lewis: The data demonstrate that time to response can be quite delayed in some patients, including many months after starting treatment. Therefore, even if patients are not responding right away, as long as there is no obvious progression and they are tolerating the therapy well, I would advise to continue with infusions in hope of a delayed response. In addition, even though cemiplimab is tolerated very well by most patients, there were some significant autoimmune events. Therefore, patients on this therapy, like other immune therapies, need to be monitored very closely.
About Dr. Lewis
Karl Lewis, MD, is a Professor in the Division of Medical Oncology at the University of Colorado Anschutz Medical Campus in Denver, Colorado. He specializes in the treatment of patients with skin cancer, including malignant melanoma and BCC. Dr. Lewis is a member of the American Society of Clinical Oncology, the Society for Melanoma Research, and the Southwest Oncology Group. He serves as a principal investigator or co-investigator of several clinical trials focusing on the development of novel therapeutics for patients with melanoma, and has authored or coauthored numerous publications in peer-reviewed journals.
For More Information
Lewis K, Peris K, Sekulic A, et al (2022). Primary analysis of phase 2 results for cemiplimab in patients with metastatic basal cell carcinoma who progressed on or were intolerant to hedgehog inhibitors. American Association of Cancer Research Annual Meeting. Abstract CT165/8.
Oncology Data Advisor (2021). Cemiplimab approval for locally advanced/metastatic basal cell carcinoma. Available at: https://oncdata.com/news/cemiplimab-approval-for-locally-advanced-metastatic-basal-cell-carcinoma?highlight=WyJjZW1pcGxpbWFiIiwiY2VtaXBsaW1hYidzIl0=
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of Oncology Data Advisor.