Effectiveness and safety of weekly paclitaxel and cetuximab as a salvage chemotherapy following immune checkpoint inhibitors for recurrent or metastatic head and neck squamous cell carcinoma: A multicenter clinical study

Abstract

Objectives: The benefit of sequential therapy after immune checkpoint inhibitor (ICI) treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) has been recently reported. Furthermore, there is a growing interest in the impact of cetuximab (Cmab)-containing salvage chemotherapy (SCT) and the therapeutic efficacy and adverse events (AEs) of Cmab administration prior to ICI administration.

Materials and methods: We retrospectively reviewed the medical records of 52 patients with R/M HNSCC treated with SCT (weekly paclitaxel [PTX], n = 7, or weekly PTX and Cmab [PC], n = 45).

Results: The objective response rate (ORR) and a disease control rate (DCR) was 53.3% and 91.1% in the PC group and 42.9% and 57.1% in the PTX group, respectively. There was a significant difference in the DCR between the PC and PTX groups (p = 0.0143). The overall survival (OS) and progression-free survival were significantly better in the PC group than in the PTX group. On the other hand, the incidence of drug-induced interstitial pneumonia (DI-IP) in R/M HNSCC patients who received SCT was 21.2%. Patients in the PC group were divided according to whether they received Cmab (Group A) or did not receive Cmab (Group B) as palliative therapy prior to ICIs. Group B had a significantly better OS than Group A. Furthermore, our findings suggest that the incidence rate of DI-IP during SCT might be higher in Group B.

Conclusion: Although PC following ICIs shows dramatic efficacy, careful monitoring of AEs, including DI-IP, is recommended.

Fig 1

Kaplan–Meier curves for (A) overall survival and (B) progression-free survival in all R/M HNSCC patients who received SCT following nivolumab treatment. There were significant differences in overall survival (C) and progression-free survival (D) between the patients administered PC and those administered PTX (p = 0.0082 and p = 0.0240, respectively). R/M HNSCC, recurrent or metastatic head and neck squamous cell carcinoma; PC, combined chemotherapy of weekly paclitaxel and cetuximab; PTX, paclitaxel; SCT, salvage chemotherapy.

Fig 2. CT imaging of two patients with DI-IP.

(A, B) A 67-year-old male patient with hypopharyngeal carcinoma after definitive CRT for primary disease with developing axillary lymph node metastasis. After PD with nivolumab, the patient underwent nine cycles of PC therapy. He was asymptomatic at the time of the CT scan, which was performed to assess the effectiveness of his treatment, and his KL-6 level was elevated to 550 U/ml (reference range: <500U/ml). However, later developed symptoms of dyspnea of the patient and was diagnosed as grade 2 DI-IP. The patient improved with follow-up. (C, D) A 57-year-old male patient with maxillary carcinoma after curative CRT for the primary disease developed localized recurrence where radical excision was impossible. After PD with nivolumab, he underwent nine cycles of PC therapy. He developed respiratory symptoms, such as fever and cough, and a CT scan to investigate the source of inflammation showed non-distracting frosted glass shadows in both lung fields. The serum KL-6 level was elevated to 860 U/ml. The patient was diagnosed as grade 3 DI-IP. He was treated with steroid pulse therapy and improved. CT, computerized tomography; DI-IP, drug-induced interstitial pneumonia; CRT, concurrent chemoradiotherapy; PD, progressive disease.

Fig 3

Kaplan–Meier curves for the overall survival (A) and the progression-free survival (B) in R/M HNSCC patients after PTX + Cmab following nivolumab. (A) The overall survival of patients who had received Cmab prior to nivolumab was significantly inferior to that of patients who had not received Cmab before treatment (log-rank test, p = 0.0086). (B) The progression-free survival of patients treated with Cmab before nivolumab was not significantly inferior to that of patients who did not received Cmab before treatment. Cmab, cetuximab; PTX, paclitaxel; R/M HNSCC, recurrent or metastatic head and neck squamous cell carcinoma.