Comparing Safety Profiles of Checkpoint Inhibitors in cSCC

This video series has been produced independently by Dermatology Times and supported through an educational grant by Sun Pharmaceuticals.

Dr. Chandra examines the safety profiles of the checkpoint inhibitors, cautioning that patient numbers remain small and cross-trial comparisons imperfect. Across the anti-PD-1 and anti-PD-L1 agents, grade 3/4 toxicity generally ranges from roughly zero to three percent, already low. Looking more closely, cosibelimab, the newest anti-PD-L1 agent with additional ADCC activity, appears to show somewhat lower grade 3/4 toxicity, but she stresses that the drug was studied largely outside the United States in relatively few patients, so the signal must be read with caution.

Dr. Patel describes himself as a skeptical optimist, wanting healthy skepticism to guard against harm while remaining hopeful about a positive signal. He draws an instructive parallel to hedgehog pathway inhibitors in basal cell carcinoma, where vismodegib and later sonidegib were treated as synonymous for years before accumulated experience revealed meaningful differences in toxicity and drug distribution. He anticipates a similar story may unfold between PD-1 and PD-L1 inhibitors, and offers a mechanistic hypothesis: sparing PD-L2, which is expressed in normal tissues such as lung, might reduce certain toxicities, yet because PD-L2 also drives immune evasion in squamous cell carcinoma, agents targeting PD-1 may achieve the robust responses seen in the neoadjuvant setting.

Dr. Carr endorses the measured view, noting that many of these high-risk patients carry significant comorbidities, so a genuine safety advantage could meaningfully influence agent selection. In closing thoughts, both panelists return to the value of early multidisciplinary discussion and frame the field as undergoing a true paradigm shift. Dr. Patel notes that the case patient ultimately received cosibelimab, achieving a partial response at six months and continuing without significant toxicity.

In the next episode, "Case 2: When to Involve Oncology in a Mohs-Eligible cSCC," Dr. Patel opens the program's second case, a 72-year-old with a rapidly enlarging forehead tumor and a telling tingling sensation, as Dr. Carr weighs whether it belongs in the operating room.