Clinical Outcomes of Cetuximab and Paclitaxel after Progression on Immune Checkpoint Inhibitors in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Abstract

Background and Objectives: In recent years, the effectiveness of chemotherapy after immune checkpoint inhibitor administration has attracted attention in various cancers, including head and neck cancers. However, individual assessments of the administered chemotherapy regimens are insufficient. This study aimed to evaluate the efficacy and safety of chemotherapy after immune checkpoint inhibitor administration in recurrent metastatic head and neck cancer by focusing on a single regimen. Materials and Methods: We retrospectively reviewed clinical and radiological data from the medical records of 18 patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who received systemic chemotherapy with weekly cetuximab and paclitaxel (Cmab + PTX) after progression following immune checkpoint inhibitor (ICI) therapy. The objective response rate (ORR) and disease control rate (DCR) were assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Adverse events (AEs) were recorded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Results: In all patients, the ORR, DCR, median PFS, and median OS were 44.4%, 72.2%, 3.8 months, and 9.6 months, respectively. Regarding AEs, three patients developed grade 3 neutropenia. Grade 3 anemia, paronychia, asthenia, and peripheral neuropathy were observed in one patient each. There were no treatment-related deaths. Conclusions: Cmab + PTX was shown to maintain high efficacy and acceptable safety for R/M HNSCC that progressed after ICI therapy. Further research is needed to establish optimal treatment sequences and drug combinations for recurrent R/M HNSCC.

Safety and preliminary activity of pembrolizumab‑carboplatin‑paclitaxel in heavily pretreated and/or fragile patients with PDL1‑positive recurrent/metastatic head and neck cancer

“…Although our results cannot be compared to those from a large phase III trial, the fact that only half of the patients in Keynote-048 received second-line therapy after IO, while in the current study the median number of treatment lines before pembro + CP was 3, with up to 80% of our patients receiving prior therapy with anti-PD(L)1 agents, may explain the prolonged survival times achieved (2). Indeed, prospective, and retrospective evidence suggests sequential treatment with ICIs followed by salvage chemotherapy associates with longer survival (22)(23)(24)(25)(26)(27). In addition, the use of ICI rechallenge may also allow to improve outcomes in patients with R/M SCCHN and in other entities such as NSCLC (25,(28)(29)(30).…”

“…In the Keynote-B10 study mentioned before, there were no differences between using three-weekly paclitaxel (175 mg/m 2 d1) and weekly paclitaxel (100 mg/m 2 d1,8), suggesting that weekly paclitaxel may be similar in terms of efficacy with a potentially more favourable toxicity profile (11). Interestingly, taxane-based weekly chemotherapy combined with cetuximab after progression to ICIs has been reported to achieve higher responses with a favorable impact in survival compared to historical data from the pre-ICI era (22)(23)(24)(25)(26)(27). For all these reasons, weekly taxane-based chemotherapy should be further evaluated -and compared with three-weekly taxane-based regimens (either in combination or sequentially with anti-PD(L)1 agents in R/M SCCHN).…”

Real-world Data of Paclitaxel and Cetuximab in Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck

“…Regarding the positioning of weekly paclitaxel plus cetuximab as a 2L scheme in the immunotherapy era, Suzuki et al (18) published in 2021 a study using this regimen in eighteen R/M HNSCC patients after progression following immune checkpoint inhibitor (ICI) therapy. This study showed a median PFS and OS of 3.8 months and 9.6 months, respectively (18).…”

“…Regarding the positioning of weekly paclitaxel plus cetuximab as a 2L scheme in the immunotherapy era, Suzuki et al (18) published in 2021 a study using this regimen in eighteen R/M HNSCC patients after progression following immune checkpoint inhibitor (ICI) therapy. This study showed a median PFS and OS of 3.8 months and 9.6 months, respectively (18). In this sense, Sato et al (19) in a retrospective study in patients with R/M head and neck cancer showed that the sequential treatment with anti-PD-1 therapy followed by paclitaxel-based chemotherapy could be a good strategy to maximize the efficacy of chemotherapy in this type of patients.…”

“…This is also because there is no established standard 2L therapy, as the treatment is mainly palliative (24) and these patients have very poor prognosis with a low response rate and short survival (25). Paclitaxel and cetuximab have also been shown to maintain high efficacy and acceptable safety for R/M HNSCC that progressed after immune checkpoint inhibitor therapy (18).…”