Neoadjuvant cemiplimab-rwlc (Libtayo) shows promise as a frontline therapy for locally advanced basal cell carcinoma (BCC) of the head and neck, according to phase 2 trial data (NCT05929664). In a study of 35 HHI-naive patients, researchers reported an objective response rate (ORR) of 60.1% and a surgical benefit rate of 42.9%, potentially allowing patients to avoid organ-sacrificing surgeries.
Shifting Treatment Sequences for Basal Cell Carcinoma
Hedgehog inhibitor (HHI) therapy has served as a systemic alternative for locally advanced BCC. However, tolerability issues often force patients to discontinue HHI treatment prematurely. By moving immunotherapy to the neoadjuvant setting—before HHI exposure—clinicians aim to capture patients earlier in the treatment algorithm.
According to Hannah Kenny, MD, a fourth-year resident in the Otolaryngology program at Sidney Kimmel Medical College, the rationale is to provide a therapy that is generally better tolerated while targeting a broader patient population. Joseph M. Curry, MD, a clinician at Jefferson Health, notes that this approach seeks to optimize patient outcomes by potentially avoiding the morbidity associated with surgery or radiation.
Clinical Outcomes and Surgical Benefit Rates
The phase 2 trial, led by investigators at Thomas Jefferson University, utilized a response-adaptive design. Patients were reassessed after two treatment cycles to determine if continued immunotherapy could deepen the tumor response or if surgical intervention was necessary.
Key findings from the 35 evaluable patients include:
- Objective Response Rate: 60.1% (95% CI, 42.1%-76.1%).
- Disease Control Rate: 91.4% (95% CI, 76.9%-98.2%).
- Surgical Benefit Rate: 42.9% (95% CI, 26.3%-60.6%), defined as avoiding the sacrifice of an organ at risk—such as the nose, eyelid, or ear—identified prior to treatment.
Preliminary analyses suggest a correlation between RECIST-defined radiographic responses and pathologic tumor responses. Approximately 40% of patients who demonstrated a RECIST response achieved a major or complete pathologic response, compared with 0% of non-responders.
Safety and Quality of Life Considerations
Neoadjuvant cemiplimab demonstrated a favorable safety profile compared with standard-of-care HHI therapy. Treatment-related adverse events (AEs) occurred in 35.3% of patients, with the majority classified as grade 1 or 2. Pruritus and fatigue were the most frequently reported side effects.
Only one patient experienced a grade 3 event (myalgia), which resulted in treatment discontinuation. Dr. Curry emphasized that the ability to de-escalate surgery without compromising safety is a significant clinical goal, though further long-term data is required to confirm the durability of these outcomes.
The study utilized surgical benefit rate as a clinician-reported end point. This metric tracks whether a patient’s actual surgery was compared with the pretreatment plan to determine whether they achieved a benefit or avoided sacrifice of an organ that was determined to be at risk prior to treatment.
Future Directions in Immunotherapy Research
While the initial results are favorable, researchers are currently analyzing pre- and post-treatment tumor specimens to identify potential biomarkers. These studies aim to clarify which patients are most likely to respond to cemiplimab and how the immune microenvironment changes during the course of treatment.
Dr. Curry noted that because basal cell cancers can be difficult to measure accurately via imaging alone, the team relied on clinical caliper measurements to track progress. Future research will likely focus on larger trials, potentially exploring combination therapies to further augment patient responses.
Frequently Asked Questions
What is the primary advantage of using cemiplimab in the neoadjuvant setting?
According to the study authors, cemiplimab is generally better tolerated than HHI therapy, allowing patients to complete treatment and potentially avoid the morbidity of organ-sacrificing surgeries.
How is “surgical benefit” defined in this study?
It is a clinician-reported end point where the actual surgery performed is compared against the pre-treatment surgical plan. A benefit is recorded if the patient avoids the sacrifice of an organ at risk (e.g., the eye or nose) that was initially slated for removal.
What were the most common side effects observed?
Patients primarily experienced grade 1 or 2 events, most notably pruritus and fatigue. Serious adverse events leading to discontinuation were rare, occurring in only one patient.
Is this treatment currently standard of care?
This data comes from a phase 2 study. While results are promising, researchers stress the need for larger trials and long-term follow-up to confirm these findings and establish new clinical practice standards.
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