Cemiplimab in Resectable NSCLC: Not Currently Recommended
Cemiplimab (Libtayo) is not currently recommended for resectable non-small cell lung cancer, as it has no established role in the neoadjuvant or adjuvant setting for operable disease. The drug's evidence base is exclusively in the metastatic/advanced disease setting, where it demonstrates significant efficacy as both monotherapy and in combination with chemotherapy 1, 2, 3.
Current Evidence Base for Cemiplimab
Metastatic Disease - Where Cemiplimab IS Indicated
For PD-L1 ≥50% (Monotherapy):
- Cemiplimab monotherapy achieved median OS of 26.1 months versus 13.3 months with chemotherapy (HR 0.57) in the EMPOWER-Lung 1 trial at 35-month follow-up 1, 2, 4
- Five-year OS probability was 29.0% for cemiplimab versus 15.0% for chemotherapy, with patients having PD-L1 ≥90% deriving the largest clinical benefits 2
- FDA and EMA approved cemiplimab for treatment-naïve metastatic NSCLC with PD-L1 ≥50% on tumor cells 1
For All PD-L1 Levels (Combination with Chemotherapy):
- In squamous cell carcinoma with PD-L1 1%-49%, cemiplimab plus chemotherapy achieved median OS of 22.3 months versus 13.8 months with chemotherapy alone (HR 0.61) 1
- The EMPOWER-Lung 3 trial demonstrated median OS of 21.9 months with cemiplimab plus chemotherapy versus 13.0 months with chemotherapy alone (HR 0.71), irrespective of PD-L1 expression or histology 3
Why Cemiplimab Is Not Used in Resectable Disease
Lack of Neoadjuvant/Adjuvant Data
No clinical trial evidence exists for cemiplimab in the resectable setting - all major neoadjuvant immunotherapy trials have utilized other PD-1/PD-L1 inhibitors 5, 6:
- CheckMate-816: nivolumab plus chemotherapy 5, 6
- KEYNOTE-671: pembrolizumab plus chemotherapy 5
- IMpower010: adjuvant atezolizumab 5
- NADIM: nivolumab plus chemotherapy 5
Established Neoadjuvant Options for Resectable NSCLC
For patients with resectable stage IB (≥4 cm) to IIIA NSCLC, the evidence-based options are:
- Nivolumab plus platinum-doublet chemotherapy (CheckMate-816 regimen) - achieves pathologic complete response rates of 24-25% 5, 6
- Pembrolizumab plus platinum-doublet chemotherapy - standard regimen is carboplatin/pemetrexed for adenocarcinoma 5, 7
- These regimens are recommended by ASCO, NCCN, and ESMO for resectable disease 5, 6
Clinical Algorithm for Your Patient
For a patient with resectable NSCLC:
- Confirm resectability and stage (IB ≥4 cm to IIIA) 5, 6
- Test for actionable mutations (EGFR, ALK, ROS1) - if positive, targeted therapy takes precedence 5, 6
- Offer neoadjuvant chemo-immunotherapy with nivolumab or pembrolizumab (NOT cemiplimab) plus platinum-doublet chemotherapy 5, 6
- PD-L1 testing is NOT required for patient selection in the neoadjuvant setting, as benefit is seen across all PD-L1 levels 5
- Administer 2-4 cycles of neoadjuvant therapy 5, 6
- Perform surgery 4-6 weeks after completing neoadjuvant therapy 5
- Consider adjuvant immunotherapy for 1 year in responders (those achieving major pathological response or pathological complete response) 5
Important Caveats
Do not extrapolate metastatic data to resectable disease - the biology, treatment goals, and risk-benefit calculations differ fundamentally between these settings 1, 5.
Cemiplimab remains an excellent option for metastatic NSCLC with comparable or potentially superior efficacy to pembrolizumab in network meta-analyses, but this does not translate to a role in resectable disease 8, 9.
If your patient progresses to metastatic disease after surgery, cemiplimab becomes a valid first-line option, either as monotherapy (if PD-L1 ≥50%) or combined with chemotherapy (any PD-L1 level) 1, 3.