Here’s a breakdown of the key takeaways regarding the evolving role of immunotherapy in nonmelanoma skin cancers, based on the provided text:
1. Adjuvant Immunotherapy Shows Promise, But Questions Remain:
KEYNOTE-630 Trial (Pembrolizumab): this trial investigated adjuvant pembrolizumab after surgery and radiation for high-risk locally advanced cutaneous squamous cell carcinoma (LA cSCC).
Positive: It demonstrated a significant reduction in recurrence.
Criticisms/Unanswered Questions:
Timing of Treatment: The 4-month window between radiation and starting immunotherapy might be too long,as some patients recur rapidly within this period. Earlier intervention coudl be more beneficial.
Overall Survival (OS) Benefit: as of the discussion, there was no demonstrated OS benefit. This is partly attributed too a crossover arm where placebo patients who recurred received PD-1 therapy (like pembrolizumab) and frequently enough responded well, masking a potential OS difference.
C-POST Trial (Cemiplimab): This trial also explored adjuvant cemiplimab. The speaker is awaiting its results but hopes it will also show a benefit. Overall Hope for Adjuvant Immunotherapy: Despite the unanswered questions, the speaker believes the aggregate data from these trials suggest that adjuvant immunotherapy is an effective therapy that dramatically reduces recurrence. They hope it will become a standard of care for surgery-first patients, especially when excessive morbidity is not a concern.
2. Neoadjuvant Immunotherapy is Highly Exciting:
Positive Early Results: A trial with cemiplimab showed exciting results in the neoadjuvant setting (treatment before surgery).
Pathologic Complete response (pCR): In 79 patients, there was a 50% pCR rate.
Confirmatory Phase 3 Trial Underway: The NRG Oncology HN014 trial is a large phase 3 study comparing neoadjuvant immunotherapy to the standard surgery-first approach.
Optimism for a new Standard of care: the speaker is optimistic that neoadjuvant immunotherapy will lead to benefits and potentially become a new standard of care for patients.
3. Evolving Standards of Care:
Adjuvant Immunotherapy: the speaker hopes adjuvant immunotherapy will be “ingrained in our future standards of care” for surgery-first patients, based on the positive recurrence reduction seen in trials like KEYNOTE-630 and C-POST.
Neoadjuvant Immunotherapy: The ongoing phase 3 trial for neoadjuvant immunotherapy is expected to potentially establish it as a new standard of care.
the broader takeaways are:
Immunotherapy is a rapidly advancing field in nonmelanoma skin cancers.
Both adjuvant and neoadjuvant approaches are showing significant promise in reducing recurrence and achieving responses.
While adjuvant immunotherapy has demonstrated recurrence reduction, further research is needed to confirm overall survival benefits and optimize treatment timing.
Neoadjuvant immunotherapy is generating considerable excitement with early positive results, and a large phase 3 trial is poised to define its role in future treatment paradigms.
The ultimate goal is to integrate these immunotherapies into the standard of care for appropriate patient populations.
