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Platinum-Based Therapy Superior in Study of Upper GI Tumors
Key clinical point: ERCC1 was not validated as a predictive marker of platinum sensitivity in upper GI tumors, though the study did support the use of fluorouracil, leucovorin, and oxaliplatin.
Major finding: The median progression-free survival in the fluorouracil, leucovorin, and oxaliplatin arm was 5.7 months versus 2.9 in the irinotecan and docetaxel arm (hazard ratio, 0.71; P = .02).
Study details: A phase 2 study of 200 untreated patients with unresectable advanced or metastatic HER2-negative adenocarcinoma of the esophagus, stomach, or gastroesophageal junction.
Disclosures: The study was supported by the National Cancer Institute. Dr. Iqbal reported receiving honoraria from Celgene, Eisai, and F. Hoffmann–La Roche; serving a consulting or advisory role for F. Hoffmann–La Roche; serving on the speakers’ bureau for Celgene and Eisai; and receiving research funding from Bayer and Onyx.
Iqbal S et al. J Clin Oncol. 2019 Dec 9. doi: 10.1200/JCO.19.00925.
Platinum drugs (mainly cisplatin or oxaliplatin) are included in standard chemotherapy regiments for advanced and metastatic esophageal, gastroesophageal, and gastric cancers. However, platinum drugs have the potential for significant toxicity and their use in this setting is generally palliative. Platinum drugs act at least in part because of platinum-DNA adducts. The protein (and gene) ERCC1 is critical to the nucleotide excision repair pathway that may counteract the effects of platinum drugs; therefore, it has been postulated that higher ERCC1 expression may affect platinum drug efficacy, and previous retrospective studies suggested as much. However, in the accompanying phase 2 study, the platinum-containing regimen FOLFOX (5-FU + oxaliplatin) was superior or equal to the comparator regimen IT (irinotecan + docetaxel), regardless of the level of ERCC1 expression. It may be that other pathway components or other pathways are involved and overcome the effects of ERCC1 expression.—Mark A. Klein, MD