Merck & Co., Inc., Rahway, NJ
Dandan Zheng , Ali Mojebi , Christopher M. Black , Hilde Giezek , Niroshini Naicker , Chiara Vanetta , Sam Keeping , Sanjay Merchant , Marcin Radoslaw Dzienis
Background: The single-arm, phase IV, KEYNOTE-B10 (KNB10) trial demonstrated the antitumor effect of the KNB10 regimen for 1L treatment of R/M HNSCC. It is critical to understand the comparative efficacy of the KNB10 regimen versus other recommended interventions in 1L R/M HNSCC, using advanced evidence synthesis methodologies, to inform clinical decision making. Methods: A systematic literature review, conducted on October 31, 2023, identified 25 randomized controlled trials evaluating 1L interventions in R/M HNSCC, of which six evaluated recommended interventions and formed a connected network. Of these, KEYNOTE-048 was determined to be the most similar study to the disconnected, single-arm, KEYNOTE-B10 trial. Therefore, individual patient-level data from KEYNOTE-B10 final analysis were reweighted and matched to KEYNOTE-048 via a MAIC in terms of metastatic disease, PD-L1 Combined Positive Score, ECOG performance status, primary tumor location as well as HPV status, sex, race, age, and smoking status. KEYNOTE-B10 was then considered an additional treatment arm of KEYNOTE-048 and was incorporated in the network. Fixed-effect NMA models in Bayesian framework were then used to estimate odds ratios of objective response rate (ORR), with 95% credible intervals, for comparisons between KNB10 and other interventions recommended for 1L R/M HNSCC. Results: Results from the fixed-effects NMA are summarized in the table. For ORR, the KNB10 regimen was more efficacious compared to pembrolizumab+platinum+5-FU, cetuximab+platinum+5-FU, platinum+5-FU, cisplatin+paclitaxel, cisplatin, 5-FU, and methotrexate (p< 0.05). There was no statistically significant difference in ORR between the KNB10 regimen and cetuximab+cisplatin+docetaxel. Conclusions: This NMA with MAIC suggests patients treated with the KNB10 regimen had improved or comparable ORR outcomes versus other recommended 1L interventions for R/M HNSCC, which further reinforces the combination therapy of pembrolizumab+platinum+taxane as an acceptable alternative 1L treatment option for R/M HNSCC. Future analyses should additionally compare survival outcomes between the KNB10 regimen and other recognized interventions in this patient population.
Comparator Regimen | Pembrolizumab + carboplatin + paclitaxel ORR odds ratio (95% credible interval) |
---|---|
Pembrolizumab + platinum + 5-FU | 1.69 (1.04, 2.74) |
Cetuximab + platinum + 5-FU | 1.64 (1.01, 2.66) |
Platinum + 5-FU | 3.69 (1.94, 7.05) |
Cisplatin + paclitaxel | 4.45 (1.84, 10.85) |
Cetuximab + cisplatin + docetaxel | 1.6 (0.88, 2.89) |
Cisplatin | 8.39 (3.13, 22.64) |
5-FU | 11.12 (4.01, 30.91) |
Methotrexate | 11.76 (4.33, 32.06) |
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