Leucovorin

Meta-analysis of 40 RCTs (11,576 patients) shows surgical-based locoregional therapies (LRTs) for nonmetastatic hepatocellular carcinoma (HCC) yield best outcomes; embolization-based LRTs poorer. Hierarchical efficacy observed: surgery with adjuvant therapy > surgery alone > radiofrequency ablation (RFA) > microwave ablation (MWA) and radiotherapy (RT) > hepatic arterial infusion chemotherapy (HAIC) > transarterial chemoembolization (TACE) > transarterial radioembolization (TARE) and transarterial bland embolization (TAE). Findings suggest LRT remains crucial in HCC treatment, with some forms preferred over others.

The ARMANI trial shows that switching to maintenance ramucirumab–paclitaxel after 3 months of induction chemotherapy improves outcomes for patients with unresectable HER2-negative G/GEJC.

Onvansertib plus FOLFIRI/bevacizumab showed increased clinical activity in second-line treatment of KRAS-mutated metastatic colorectal cancer, with a 26.4% overall response rate. Patients without prior bevacizumab exposure had a 76.9% ORR and median PFS of 14.9 months, leading to study termination early. The regimen is now being evaluated as a first-line therapy.

No difference in overall survival between FOLFOXIRI plus bevacizumab and FOLFOX/FOLFIRI plus bevacizumab in colorectal cancer patients with liver-only metastases, regardless of RAS/BRAF V600E variant status and tumor sidedness. FOLFOX/FOLFIRI-bevacizumab is supported for these patients.

Mastrantoni et al. identified better first-line chemotherapy regimens for unresectable advanced or metastatic pancreatic cancer in a meta-analysis. Best regimens for progression-free survival included gemcitabine plus nab-paclitaxel alternating with FOLFOX, PAXG, NALIRIFOX, FOLFIRINOX, and gemcitabine plus nab-paclitaxel. For overall survival, best regimens were PAXG, gemcitabine plus nab-paclitaxel alternating with FOLFOX, NALIRIFOX, FOLFIRINOX, and gemcitabine plus nab-paclitaxel. PAXG and gemcitabine plus nab-paclitaxel alternating with FOLFOX need phase 3 trials. NALIRIFOX and FOLFIRINOX are preferred for patients who can tolerate them, with gemcitabine plus nab-paclitaxel as a viable alternative for those unfit for triplet therapy.

Zolbetuximab, a CLDN18.2-targeted IgG1 monoclonal antibody, combined with frontline chemotherapy, extended PFS and OS in HER2-negative, locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma patients positive for CLDN18.2, according to phase 3 SPOTLIGHT and GLOW trials. The FDA approved zolbetuximab in October 2024 for first-line treatment of these patients. Median PFS was 9.2 months with zolbetuximab vs 8.2 months with placebo, and median OS was 16.4 months vs 13.7 months, respectively. Zolbetuximab was also approved in Japan and Europe in 2024.

Cindy Medina Pabon discusses the FDA approval of zolbetuximab-clzb (Vyloy) for HER2-negative, Claudin 18.2-positive gastric or gastroesophageal junction adenocarcinoma. Zolbetuximab, combined with chemotherapy, was approved based on SPOTLIGHT and GLOW trials, showing survival benefits. This marks a significant advancement in targeted therapy for gastric cancer.

Merrimack Pharmaceuticals, a biotech company focused on cancer treatment, has five oncology candidates in clinical development. Its most advanced candidate, MM-398, is in a global phase III study for pancreatic cancer. Merrimack also has candidates like MM-121, developed with Sanofi, in various cancer trials. Despite significant operating losses, the company's IPO raised $100.5 million, funding operations into the second half of 2013.

FDA approves 420-mg trastuzumab-strf for HER2-overexpressing cancers, and zolbetuximab for CLDN18.2-positive gastric/GEJ adenocarcinoma. FDA delays decision on sotorasib plus panitumumab for KRAS G12C-mutated CRC to Jan 2025. LP-184 granted fast track designation for glioblastoma treatment.

Astellas Pharma’s Vyloy (zolbetuximab-clzb) approved by FDA for first-line treatment of CLDN18.2-positive, HER2-negative gastric or gastro-oesophageal junction adenocarcinoma, in combination with chemotherapy. Supported by SPOTLIGHT and GLOW trials, Vyloy shows improved progression-free and overall survival. Now approved in US, EU, UK, Japan, and South Korea.