Jacob’s ladder.

Top Line: Just like in breast cancer, trastuzumab improves overall survival for patients with advanced HER2(+) esophagogastric cancers. So the same should hold true for the addition of pertuzumab, right?
The Study: The phase 3 JACOB trial randomized 780 patients with metastatic esophagogastric junction (EGJ) and gastric cancers across almost 200 oncology clinics to standard chemo with trastuzumab +/- pertuzumab every 3 weeks. Chemo was physician’s choice of 5FU continuous infusion or cisplatin/Xeloda. Toxicity profiles were virtually identical other than a doubling of grade 3-4 diarrhea with the addition of pertuzumab from 6→13%. The primary endpoint of median overall survival was 18 months with versus 14 months without pertuzumab, translating to a hazard ratio of death of 0·84 (95% CI 0·71–1·00; p=0·057). And now for the biggest news of all: For the first time ever, an industry-sponsored trial may have understated results. The Roche-sponsored authors unequivocally conclude “Adding pertuzumab to trastuzumab and chemotherapy did not significantly improve overall survival.”
Bottom Line: The addition of pertuzumab to trastuzumab and chemo for metastatic HER2(+) esophagogastric cancers improved median survival by over 3 months, but these authors must be spooked by the current COI panic. | Tabernero, Lancet Oncol 2018


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