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. 2024 Nov 25:14:1458479.
doi: 10.3389/fonc.2024.1458479. eCollection 2024.

Salvage chemotherapy after progression on immunotherapy in recurrent/metastatic squamous cell head and neck carcinoma

Sandra Llop  1 , Maria Plana  1 , Sara Tous  2   3 , Angelica Ferrando-Díez  4 , Jesús Brenes  1 , Marc Juarez  5 , Zara Vidales  1 , Esther Vilajosana  1 , Isabel Linares  5 , Lorena Arribas  6 , Maria Duch  7 , Marta Fulla  8 , Aina Brunet  8 , Alicia Lozano  5 , Beatriz Cirauqui  4 , Ricard Mesía  4 , Marc Oliva  1
Affiliations

Salvage chemotherapy after progression on immunotherapy in recurrent/metastatic squamous cell head and neck carcinoma

Sandra Llop et al. Front Oncol. .

Abstract

Objectives: Anti-PD-(L)1 agents changed the landscape of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) treatment. Previous studies showed improved response rates to salvage chemotherapy (SCT) after progression to anti-PD-(L)1 agents. This study aims to evaluate the outcomes of SCT and to identify predictors of response and survival in patients with R/M HNSCC.

Materials and methods: Retrospective cohort analysis of 63 R/M patients treated with SCT after antiPD-(L1)-based therapy between January 2015 and August 2022. The overall response rate (ORR) was evaluated. Progression-free survival (PFS) and overall survival (OS) were estimated with Kaplan-Meier method. Progression-free survival 2 was calculated from anti-PD-(L)1-therapy start until progression to SCT (PFS2-I). Logistic regression and Cox regression analyses were performed to identify predictors of outcome.

Results: A total of 63 patients were included: 76% were men, and median age was 60 years. PD-L1 status was available in 68% (61% positive). Up to 71% received SCT as third line or beyond. ORR to SCT was 49% with higher rates in PD-L1 positive tumors, 71% vs. 18% (p=0.001), and cetuximab-containing regimens, 68% vs. 39% (p=0.026). PD-L1 status was the only predictor of ORR in the adjusted model (OR=8.6, 95% CI 1.7-43.0). OS and PFS were 9.3 months (95% CI, 6.5-12.3) and 4.1 months (95% CI, 3.0-5.8) respectively. PFS2-I was 8.6 months (95% CI, 6.6-10.5). In the multivariate analysis, PD-L1 was the only independent factor for OS (HR=0.3; 95% CI, 0.1-0.7), PFS (HR=0.2; 95% CI, 0.1-0.5; p<0.001), and PFS2-I (HR=0.2; 95% CI 0.1-0.5; p<0.001).

Conclusion: PDL1 status appeared as a strong predictor of response of efficacy for SCT after anti-PD-(L)1 agents. Patients receiving cetuximab-containing regimens trended towards greater benefit. This highlights the importance of treatment sequencing and personalized treatment strategies.

Keywords: HNSCC; SCT; anti-PD-(L)1; head and neck; immunotherapy; salvage chemotherapy; squamous cell carcinoma; treatment sequencing.

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Conflict of interest statement

SL has speaker’s Bureau/Travel accommodations expenses: MSD, Merck. MP has speaker’s Bureau/Travel accommodations expenses: Eisai and MSD. ST has sponsorship for grants from Merck, Roche, GSK, IDT, Hologic, Seegene. AF-D has speaker’s Bureau: MSD and Angelini Pharma; and travel accommodations expenses: MSD, Lilly, Roche, Merck, BMS, and Pfizer. JB has speaker’s Bureau/Travel accommodations expenses: MSD, Merck. MJ has speaker’s Bureau/Travel accommodations expenses: MSD, Merck. ZV has speaker’s Bureau/Travel accommodations expenses: MSD, Merck. EV has speaker’s Bureau/Travel accommodations expenses: MSD, Merck. IL has speaker’s Bureau/Travel accommodations expenses: Merck. LA has advisory arrangements with Pfizer, Nutricia; Speaker’s Bureau: MSD, Merck, Nestle; Travel accommodations expenses: Nestle, Vegenat. AL has speaker’s Bureau/Travel accommodations expenses: Merck. BC has advisory arrangements: BMS, Merck and MSD; Training grants: BMS, Merck and MSD; Speaker’s Bureau/Travel accommodations expenses: BMS, Merck and MSD. RM has consulting/advisory arrangements with Pfizer, MSD, Merck KgA, Boehringer, GSK; Speakers’ Bureau: Merck KgA, MSD, Roche. MO has consulting/advisory arrangements with Merck, MSD and Transgene. Research support from Merck and Roche. The institution receives clinical trial support from Abbvie, Ayala Pharmaceutical, MSD, ALX Oncology, Debiopharm International, Merck, ISA Pharmaceuticals, Roche Pharmaceuticals, Boehringer Ingelheim, Seagen, Gilead. Speaker’s Bureau/Travel accommodations expenses: BMS, MSD, Merck. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) Overall survival to SCT by PDL-1 status. (B) Progression-free survival to SCT by PDL-1 status. (C) Progression-free survival 2 to SCT by PDL-1 status.
See this image and copyright information in PMC

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