6ER-032 Adjusted indirect comparison of cemiplimab in combination with chemotherapy vs immunotherapy alone in the first-line treatment of metastatic non-small-cell lung cancer in patients with pd-l1≥50%

Background and Importance Cemiplimab with chemotherapy is licensed for the treatment of first line adult patients with locally advanced NSCLC who are not candidates for chemoradiation, or metastatic, expressing PD-L1≥1%. Cemiplimab alone has the same indication in patients expressing PD-L1≥50%. Pembrolizumab and atezolizumab are also indicated in metastatic stage in patients with PD-L1≥50%. Aim and Objectives To know whether cemiplimab in combination with chemotherapy (ct) and mono-immunotherapy can be declared equivalent therapeutic alternatives (ETA). Material and Methods A literature search was performed in MEDLINE-PubMed for phase III randomised clinical trials (CT)with similar population and duration. An adjusted indirect comparison (IC)was performed using Bucher's method (ITC calculator). The primary endpoint was overall survival in patients with PD-L1≥50%. Therapeutic alternatives were compared with cemiplimab monotherapy. The delta value (Δ), maximum clinically irrelevant difference, was taken as the value from the ESMO-MCBS Guidelines to consider substantial benefit, HR 0.70 and its inverse 1.43 . To declare them as ETA, the GENESIS-GHEMA guidelines were applied. Results Data from CT against a common comparator, platinum-based chemotherapy, were included. The studies were similar, although the CT of cemiplimab-chemotherapy and cemiplimab included patients with stage IIIB, IIIC and IV, while the other CT only included stage IV; furthermore, the CT of cemiplimab excluded never-smokers (less than 100 cigarettes through life), and the small amount of never-smokers included on other monotherapy trials showed uncertain benefits. The following results were obtained: HR (cemiplimab vs cemiplimab+ct) 0.93 [95%CI 0.52–1.68] p 0.81; HR (cemiplimab vs pembrolizumab) 0.95 [95%CI 0.58–1.55] p 0.84; HR (cemiplimab vs atezolizumab) 0.97 [95%CI 0.59–1.60] p 0.89. According to the ETA guidelines, cemiplimab+ct, atezolizumab, pembrolizumab and cemiplimab showed 'probable clinical equivalence'. Clinically relevant differences between them cannot be discarded, since the confidence intervals exceed the equivalence margins, but this occurs at both extremes, and they can be considered as alternatives with similar effectiveness. Cemiplimab+ct presents a comparative handicap on safety because of the toxicity of chemotherapy. Conclusion and Relevance In this setting, atezolizumab, cemiplimab and pembrolizumab monotherapies can be positioned as ETA; their selection should be based on economic comparisons. Among the never-smoker subpopulation, the comparative effectiveness between immune-chemotherapy and mono-immunotherapy should be assessed. References and/or Acknowledgements Conflict of Interest No conflict of interest.