Cetuximab combined with paclitaxel or paclitaxel alone for patients with recurrent or metastatic head and neck squamous cell carcinoma progressing after EXTREME.

Prognosis of recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) remains poor. The addition of cetuximab, to platinum and fluorouracil chemotherapy (EXTREME regimen) has been shown to improve patients' outcomes in first-line settings. We conducted a retrospective, multicenter study, including HNSCC that progressed after a first line of platinum-based chemotherapy and cetuximab, treated either by paclitaxel + cetuximab (PC) or paclitaxel alone (P), between January 2010 and April 2018. The end points were overall survival (OS), progression-free survival (PFS), and overall response rates (ORR). Patients were matched according to their propensity scores, estimated with a logistic regression model. The secondary objectives were to study the safety profile and to look for prognostic and predictive factors of effectiveness. Of the 340 identified patients, 262 were included in the analysis, 165 received PC, and 97 received P. In unmatched population, ORR was 16.4% with PC and 6.2% for P. Median PFS was 2.9 months [95% Confidence Interval 2.7-3.0] for PC versus 2.5 months [2.2-2.7] for P, hazard ratio (HR) = 0.770 [0.596-0.996]. Median OS was 5.5 months [4.4-6.9] for PC versus 4.2 months [3.4-4.8] for P, HR = 0.774 [0.590-1.015]. In multivariate analysis, PC was associated with better PFS and OS. These results were consistent in matched-paired population. Previous cetuximab maintenance for more than 3 months was predictive of better OS with PC. Although the continuation of cetuximab in combination with paclitaxel after EXTREME provides moderate benefit, it could be an interesting option for selected patients.

Chevalier T ，Daste A ，Saada-Bouzid E ，Loundou A ，Peyraud F ，Lambert T ，Le Tourneau C ，Peyrade F ，Dupuis C ，Alfonsi M ，Fayette J ，Reure J ，Huguet F ，Fakhry N ，Toullec C ，Salas S ... -  《Cancer Medicine》

Efficacy and Safety of Cetuximab Plus Cisplatin Alone or in Combination With Paclitaxel in Patients With Head and Neck Squamous Cell Carcinoma: A Randomized Trial.

Zheng Y ，Dou H ，Li Q ，Sun Y ，Wang Y ，Zhang W ... -  《-》

Clinical impact of weekly paclitaxel plus cetuximab is comparable to the EXTREME regimen for recurrent/metastatic head and neck squamous cell carcinoma.

Motai R ，Sawabe M ，Kadowaki S ，Sasaki E ，Nishikawa D ，Suzuki H ，Beppu S ，Terada H ，Hanai N ... -  《-》

First-line treatment with chemotherapy plus cetuximab in Chinese patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: Efficacy and safety results of the randomised, phase III CHANGE-2 trial.

The EXTREME regimen (chemotherapy [CT; cisplatin/carboplatin and 5-fluorouracil]) plus cetuximab is a standard-of-care first-line (1L) treatment for patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN), as supported by international guidelines. The phase III CHANGE-2 trial assessed the efficacy and safety of a modified CT regimen (with a reduced dose of both components) and cetuximab versus CT for the 1L treatment of Chinese patients with R/M SCCHN. Patients were randomised to receive up to six cycles of CT plus cetuximab followed by cetuximab maintenance until progressive disease or CT alone. The primary end-point was the progression-free survival (PFS) time assessed by the independent review committee (IRC). Overall, 243 patients were randomised (164 to CT plus cetuximab; 79 to CT). The hazard ratios for PFS by IRC and overall survival (OS) were 0.57 (95% CI: 0.40-0.80; median: 5.5 versus 4.2 months) and 0.69 (95% CI: 0.50-0.93; median: 11.1 versus 8.9 months), respectively, in favour of CT plus cetuximab. The objective response rates (ORR) by IRC were 50.0% and 26.6% with CT plus cetuximab and CT treatment, respectively. Treatment-emergent adverse events of maximum grade 3 or 4 occurred in 61.3% (CT plus cetuximab) and 48.7% (CT) of patients. CHANGE-2 showed an improved median PFS, median OS and ORR with the addition of cetuximab to a modified platinum/5-fluorouracil regimen, with no new or unexpected safety findings, thereby confirming CT plus cetuximab as an effective and safe 1L treatment for Chinese patients with R/M SCCHN. NCT02383966.

Guo Y ，Luo Y ，Zhang Q ，Huang X ，Li Z ，Shen L ，Feng J ，Sun Y ，Yang K ，Ge M ，Zhu X ，Wang L ，Liu Y ，He X ，Bai C ，Xue K ，Zeng Y ，Chang X ，Chen W ，Lin T ... -  《-》

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.

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. 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). 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. 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.

Koyama T ，Kiyota N ，Boku S ，Imamura Y ，Shibata N ，Satake H ，Tanaka K ，Hayashi H ，Onoe T ，Asada Y ，Yamazaki T ，Nose T ，Ohata S ，Nagatani Y ，Kimbara S ，Funakoshi Y ，Teshima M ，Shinomiya H ，Minami H ... -  《ESMO Open》