Response rate with cetuximab used less than 3 months after immunotherapy (IO) for recurrent/metastatic head and neck squamous cell carcinomas (R/M HNSCC) compared to larger delay.
Authors: Carulla Yannick , Neidhardt Eve-Marie , Karabajakian Andy , Gauduchon Thibault , Guevara Hemerson , Roux Pierre Eric , Zrounba Philippe , Podeur Fabien , Poupart Marc , Excoffier Aude , Fayette Jerome 
Published: June 2024

e18027

Background: After failure of platinum and anti-PD1 for R/M HNSCC cetuximab in monotherapy is a standard of treatment. Previous studies with cetuximab demonstrated objective response rates (ORR) of 13%. In the INTERLINK study, cetuximab used after IO demonstrated about 20% of ORR. We speculate that this better ORR can be the reflect of a delayed response with IO or an in-body combination of IO + cetuximab since this combination showed high response rate. So we have compared response rate to cetuximab used less than 3 months after IO (<3m) vs more than 3 months (>3m). Methods: We retrospectively analyzed the files of patients treated with cetuximab in a single institution, the Centre Leon Berard in France, who were in failure after platinum and IO (pembrolizumab, nivolumab, atezolizumab, cemiplimab or durvalumab), received sequentially or in combination. All patients treated since 2015 were collected. Key exclusion criteria: previous use of anti-EGFR, use of other anti-EGFR than cetuximab. ORR was analyzed by RECIST 1.1. PFS and OS were calculated from the first administration of cetuximab to the progression or death. Results: Between 2015 and 2024, 103 patients met the inclusion criteria : median age was 66 years, 78% were male. Globally, the response rate to cetuximab was higher than expected at 43%. For the 74 patients who received cetuximab less than 3 months after the last dose of IO, the response rate was 45%, for the 29 patients who received cetuximab more than 3 months after the last dose of IO, the response rate was 41%. The previous good response to IO does not seem a predictive factor for the response to cetuximab : ORR was 40% in previous good responders vs 44%. For the whole population, the mPFS was 4 months and the mOS 8 months. For the populations <3m and >3m, the mPFS was 3.7m and 6.3m respectively and the mOS was 7.4m and 10.0m. We observed a greater difference when cetuximab is taken alone (or associated with monalizumab) vs with chemotherapy. Without chemotherapy, the response rate was 47% for the populations <3m and only 24% for the >3m. With chemotherapy the response rate was 50% for the populations <3m and 45% for the >3m. There was no significant difference in therm of mPFS and mOS. Conclusions: The use of IO less than 3 months before cetuximab lead to better ORR to cetuximab compared to a delay longer than 3 months. When cetuximab is started early after IO the benefit in terms of ORR of chemo is weak whereas it appears important later than 3 months. This difference in ORR is not clearly associated with a trend in FPS and OS. We can give three possible explanations : We just observed delayed efficacy of IO that could be visible only in the 3 months after the last infusion. We observed false progression to IO Since the IO is stable in the body, we observed a synergic effect between IO and cetuximab that cannot be seen more than 3 months after the last injection.