First-line cetuximab + platinum-based therapy for recurrent/metastatic head and neck squamous cell carcinoma: A real-world observational study-ENCORE.

ENCORE, an observational, prospective, open-label study, investigated real-world treatment practices and outcomes with cetuximab plus platinum-based therapy (PBT) in first-line (1L) recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). This multinational study aimed to investigate the long-term use of cetuximab plus PBT for 1L R/M SCCHN in a clinical setting. In particular, this study aimed to explore clinical considerations such as the decision to prescribe cetuximab plus PBT in R/M SCCHN, the mode and duration of treatment, and patient outcomes. Previously untreated patients with R/M SCCHN whose planned treatment was cetuximab plus PBT were enrolled from 6 countries. Among 221 evaluable patients, planned treatments included cetuximab plus carboplatin (31.2%), cisplatin plus 5-fluorouracil (31.7%), or carboplatin plus 5-fluorouracil (23.1%); 3.2% included a taxane, and 45.2% did not include 5-fluorouracil. Cetuximab treatment was planned for a fixed duration (≤24 weeks) in 15 patients (6.8%) and until disease progression in 206 (93.2%). Median progression-free survival and overall survival were 6.5 and 10.8 months, respectively. Grade ≥3 adverse events occurred in 39.8% of patients. Serious adverse events occurred in 25.8% of patients; 5.4% were cetuximab-related. In patients with R/M SCCHN, first-line cetuximab plus PBT was feasible and modifiable in a real-world setting with similar toxicity and efficacy as in the pivotal phase III EXTREME trial. EMR 062202-566.

Le Tourneau C ，Ghiani M ，Cau MC ，Depenni R ，Ronzino G ，Bonomo P ，Montesarchio V ，Leo L ，Schulten J ，Salmio S ，Messinger D ，Sbrana A ，Borcoman E ，Ghi MG ... -  《Cancer Reports》

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 ... -  《-》

Observational, prospective, phase 4 study in patients with first-line recurrent and/or metastatic squamous cell carcinoma of the head and neck treated with cetuximab and platinum-based therapy: DIRECT.

Cetuximab plus platinum-based therapy (PBT) followed by cetuximab maintenance until progression (EXTREME) is a guideline-recommended first-line treatment option in recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). DIRECT (Dose Intensity RElative to CeTuximab) was the first phase 4 observational study evaluating EXTREME administration in the real-world setting. The primary aim of this study was to assess the relative dose intensity of cetuximab in patients with R/M SCCHN treated with first-line cetuximab according to the EXTREME regimen. Patients were ≥18 years old and eligible to receive cetuximab/PBT. Primary endpoint was cetuximab relative dose intensity (RDI). Of prospectively enrolled patients (n = 157), 119 received ≥1 cycle of EXTREME. Practices differing from the EXTREME trial were 5-fluorouracil omission (14%), maintenance cetuximab given every other week (54%), prior cetuximab, disease-free interval <6 months. 64% of patients reached cetuximab RDI ≥80%; mean cetuximab RDI was 88%. 46% of patients received maintenance cetuximab (mean RDI, 91%). Median progression-free survival and overall survival were 4.5 and 9.4 months. No new/unexpected safety findings were observed. The DIRECT study showed that first-line cetuximab plus PBT was a feasible, beneficial first-line treatment regimen in patients with R/M SCCHN in the real-world setting.

Guigay J ，Chamorey E ，Lefebvre G ，Rotarski M ，Wagner JP ，Blot E ，Alfonsi M ，Seronde A ，Schulten J ，Peyrade F ，Le Tourneau C ... -  《-》

Clinical outcomes of platinum-based chemotherapy plus cetuximab for recurrent or metastatic squamous cell carcinoma of the head and neck: comparison between platinum-sensitive and platinum-resistant patients.

Sato H ，Tsukahara K ，Okamoto I ，Katsube Y ，Shimizu A ，Kondo T ，Hanyu K ，Fushimi C ，Okada T ，Miura K ... -  《-》

Cetuximab plus platinum-based chemotherapy in head and neck squamous cell carcinoma: a randomized, double-blind safety study comparing cetuximab produced from two manufacturing processes using the EXTREME study regimen.

Soulières D ，Aguilar JL ，Chen E ，Misiukiewicz K ，Ernst S ，Lee HJ ，Bryant K ，He S ，Obasaju CK ，Chang SC ，Chin S ，Adkins D ... -  《BMC CANCER》