As compared with platinum-based chemotherapy plus fluorouracil alone, cetuximab plus platinum-fluorouracil chemotherapy improved overall survival when given as first-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck. (ClinicalTrials.gov number, NCT00122460.)

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The administration of nab-PC as first-line therapy in patients with advanced NSCLC was efficacious and resulted in a significantly improved ORR versus sb-PC, achieving the primary end point. nab-PC produced less neuropathy than sb-PC.

Cisplatin/S-1 did not prolong OS of patients with advanced gastric or gastroesophageal adenocarcinoma compared with cisplatin/infusional fluorouracil, but it did result in a significantly improved safety profile.

Background: Claudin 18.2 (CLDN18.2) is contained within normal gastric mucosa epithelial tight junctions; upon malignant transformation, CLDN18.2 epitopes become exposed. Zolbetuximab, a chimeric monoclonal antibody, mediates specific killing of CLDN18.2-positive cells through immune effector mechanisms. Patients and methods: The FAST study enrolled advanced gastric/gastro-oesophageal junction and oesophageal adenocarcinoma patients (aged 18 years) with moderate-to-strong CLDN18.2 expression in 40% tumour cells. Patients received first-line epirubicin þ oxaliplatin þ capecitabine (EOX, arm 1, n ¼ 84) every 3 weeks (Q3W), or zolbetuximab þ EOX (loading dose, 800 mg/m 2 then 600 mg/m 2 Q3W) (arm 2, n ¼ 77). Arm 3 (exploratory) was added after enrolment initiation (zolbetuximab þ EOX 1000 mg/m 2 Q3W, n ¼ 85). The primary endpoint was progression-free survival (PFS) and overall survival (OS) was a secondary endpoint. Results: In the overall population, both PFS [hazard ratio (HR) ¼ 0.44; 95% confidence interval (CI), 0.29-0.67; P < 0.0005] and OS (HR ¼ 0.55; 95% CI, 0.39-0.77; P < 0.0005) were significantly improved with zolbetuximab þ EOX (arm 2) compared with EOX alone (arm 1). This significant PFS benefit was retained in patients with moderate-tostrong CLDN18.2 expression in 70% of tumour cells (HR ¼ 0.38; 95% CI, 0.23-0.62; P < 0.0005). Significant improvement in PFS was also reported in the overall population of arm 3 versus arm 1 (HR ¼ 0.58; 95% CI, 0.39-0.85; P ¼ 0.0114) but not in high CLDN18.2-expressing patients; no significant improvement in OS was observed in either population. Most adverse events (AEs) related to zolbetuximab þ EOX (nausea, vomiting, neutropenia, anaemia) were grade 1-2. Grade 3 AEs showed no substantial increases overall (zolbetuximab þ EOX versus EOX alone). Conclusions: In advanced gastric/gastro-oesophageal junction and oesophageal adenocarcinoma patients expressing CLDN18.2, adding zolbetuximab to first-line EOX provided longer PFS and OS versus EOX alone. Zolbetuximab þ EOX was generally tolerated and AEs were manageable. Zolbetuximab 800/600 mg/m 2 is being evaluated in phase III studies based on clinical benefit observed in the overall population and in patients with moderate-to-strong CLDN18.2 expression in 70% of tumour cells.