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Clinical Trial
. 2024 Jun;9(6):103476.
doi: 10.1016/j.esmoop.2024.103476. Epub 2024 Jun 3.

A phase II trial of paclitaxel plus biweekly cetuximab for patients with recurrent or metastatic head and neck cancer previously treated with both platinum-based chemotherapy and anti-PD-1 antibody

T Koyama  1 , N Kiyota  2 , S Boku  3 , Y Imamura  4 , N Shibata  5 , H Satake  6 , K Tanaka  7 , H Hayashi  7 , T Onoe  8 , Y Asada  9 , T Yamazaki  10 , T Nose  4 , S Ohata  4 , Y Nagatani  4 , S Kimbara  4 , Y Funakoshi  4 , M Teshima  11 , H Shinomiya  11 , H Minami  12
Affiliations
Clinical Trial

A phase II trial of paclitaxel plus biweekly cetuximab for patients with recurrent or metastatic head and neck cancer previously treated with both platinum-based chemotherapy and anti-PD-1 antibody

T Koyama et al. ESMO Open. 2024 Jun.

Abstract

Background: An important unmet need for new treatment options remains for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC) previously treated with both platinum-based chemotherapy and anti-programmed cell death protein 1 (PD-1) antibody. Retrospective studies suggest that previous treatment with immune checkpoint inhibitor might augment the efficacy of subsequent chemotherapy. Here, we conducted a phase II trial aimed to evaluate the efficacy and safety of paclitaxel plus biweekly cetuximab for patients in this setting.

Patients and methods: This was a single-arm, multicenter, phase II trial. Key eligibility criteria were R/M-HNSCC, and previous treatment with both platinum-based chemotherapy and PD-1 antibody. Paclitaxel plus biweekly cetuximab consisted of weekly paclitaxel 100 mg/m2 (days 1, 8, 15) and biweekly cetuximab 500 mg/m2 (days 1, 15) with a cycle of 28 days until progression or unacceptable toxicity. Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and adverse events (AEs) (Common Terminology Criteria for Adverse Events version 5.0).

Results: Between August 2020 and August 2022, 35 patients were enrolled, of whom 33 were assessable for response. ORR was 69.6% (95% confidence interval 51.2% to 84.4%). With a median follow-up period for survivors of 16.6 months, median PFS and OS were 5.5 and 13.3 months, respectively. DCR was 93.7%. Twenty-three patients (65%) experienced grade 3 or 4 AEs, including neutropenia (34%), infection (14%), leukopenia (11%), mucositis (8%), and pneumonitis (8%). Eight patients discontinued study treatment due to treatment-related AEs, and no treatment-related death was observed.

Conclusions: Paclitaxel plus biweekly cetuximab showed highly encouraging efficacy and manageable toxicities in R/M-HNSCC patients previously treated with both platinum-based chemotherapy and PD-1 antibody. This combination therapy warrants further investigation in this setting.

Keywords: PD-1 inhibitors; cetuximab; cisplatin; head and neck cancer; paclitaxel.

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Conflict of interest statement

Disclosure TK has received invited speaker fees from Shionogi, Merck Biopharma, and Nihon Medi-Physics. NK’s institution reports receiving research funding from Bristol Myers Squibb, AstraZeneca, Chugai Pharmaceutical, Bayer, Lilly, GSK, and Adlai Nortye; NK has received invited speaker fees from Bristol Myers Squibb, Bayer, Eli Lilly, MSD, Ono Pharmaceutical, Merck Biopharma, and Eisai, and advisory board fees from Ono Pharmaceutical and Adlai Nortye. SB has received invited speaker fees from MSD, ONO Pharmaceutical, Bristol Myers Squibb, Taiho Pharmaceutical, and Chugai Pharmaceutical. YI has received invited speaker fees from Daiichi Sankyo and MSD. NS has received invited speaker fees from Chugai Pharmaceutical, Kyowa Kirin, Pfizer, Daiichi Sankyo, Eisai, Yakult Honsha, Taiho Pharmaceutical, Takeda Pharmaceutical, Novartis, AstraZeneca, Merck Biopharma, Bayer, Eli Lilly, Ono Pharmaceutical, Nippon Kayaku, and Medicon, and advisory board fees from Kyowa Kirin and Daiichi Sankyo. HSa’s institution reports receiving research funding from Ono Pharmaceutical, Daiichi Sankyo, Taiho Pharmaceutical, Sanofi, and Asahi Kasei; HSa has received invited speaker fees from Bayer, Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly, Merck Biopharma, MSD, Ono Pharmaceutical, Sanofi, Taiho Pharmaceutical, Takeda, and Yakult Honsha. KT has reported receiving invited speaker fees from AstraZeneca, Merck Biopharma, Eisai, Bristol Myers Squibb, Ono Pharmaceutical, MSD, Chugai Pharmaceutical, Takeda Pharmaceutical, Taiho Pharmaceutical, and Novartis. HH’s institution has received research funding from Guardant Health Japan, IQVIA, Eisai, Syneos Health, EP-CRSU, EPS, Shionogi, Nippon Kayaku, Otsuka Pharmaceutical, Takeda Pharmaceutical, GlaxoSmithKline, MSD, Sanofi, Amgen, Chugai Pharmaceutical, Taiho Pharmaceutical, Nippon Boehringer Ingelheim, Bristol Myers Squibb, SRL Medisearch, Janssen Pharmaceutical, PRA Health Sciences, CMIC, Astellas Pharma, Pfizer R&D Japan G.K., Ascent Development Services, Labcorp Development Japan, Eisai, Kobayashi Pharmaceutical, Bayer, and Pfizer Japan; HH has received invited speaker fees from Ono Pharmaceutical, Merck Biopharma, Daiichi Sankyo, 3H Clinical Trial, AstraZeneca, Novartis, Chugai Pharmaceutical, Bristol Myers Squibb, Eli Lilly, Amgen, MSD, Sysmex, Pfizer Japan, Takeda Pharmaceutical, and Nippon Boehringer Ingelheim. TO’s department has reported receiving grants from MSD and Merck Biopharma; TO has received invited speaker fees from Eisai, Chugai Pharmaceutical, Taiho Pharmaceutical, and Bristol Myers Squibb, and advisory board fees from Eisai. YN has reported receiving personal honoraria as an invited speaker from Ono Pharmaceutical, Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, and Eli Lilly. HSh has reported receiving an invited speaker fee from Rakuten Medical. HM’s institution has reported receiving grants from Abbvie, Asahi-Kasei Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, Chugai, Eisai, Daiichi-Sankyo, DaiNippon Sumitomo, GSK, Insight, Kyowa-Kirin, Eli Lilly, Merck Biopharma, MSD, Nihon-Kayaku, Nihon-Shinyaku, Shionogi, Novartis, Sanofi, Teijin Pharma, Taiho, Ono Pharmaceutical, Otsuka Pharmaceutical, Sumitomo Pharma, Takeda, Tsumura, and Yakult; HM has received personal honoraria as an invited speaker from Abbvie, Asahi-Kasei Pharma, Bayer, Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi-Sankyo, Daiichi-Sankyo Espha, Eisai, Kyowa-Kirin, Eli Lilly, Meiji Seika Pharma, Merck Biopharma, Nihon Servier, Novartis, Ono Pharmaceutical, Otsuka Pharmaceutical, Pfizer, Sanofi, Shionogi, Taiho, and Takeda. All other authors have declared no conflicts of interest.

Figures

Figure 1
Figure 1
Tumor response by waterfall plot and spider plot. (A) Best percentage change from baseline in the target lesion in the efficacy analysis population (N = 33). (B) Longitudinal changes in target lesion size from baseline in the efficacy analysis population (N = 33). Responses were calculated using RECIST version 1.1. The black dashed line means 30% reduction and the red dashed line means 20% increase. CR, complete response; PD, progressive disease; PR, partial response; SD, stable disease. aPatients who were resistant to a cetuximab-containing regimen.
Figure 2
Figure 2
Survival outcomes for patients receving study teatment. Kaplan–Meier curves for progression-free survival (A) and overall survival (B) in the total population (N = 35). The x-axis represents months.
Supplemental Figure S1
Supplemental Figure S1
Flow diagram (N=35), Flow diagram of patient disposition and discontinuation details at the cut-off date.
See this image and copyright information in PMC

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