Pertuzumab and Trastuzumab Plus Chemotherapy in HER2-Positive, Metastatic Gastric or Gastroesophageal Junction Cancer
As reported in The Lancet Oncology by Tabernero et al, the phase III JACOB trial showed no significant overall survival benefit of adding pertuzumab (Perjeta) to trastuzumab (Herceptin) plus chemotherapy in first-line treatment of HER2-positive metastatic gastric or gastroesophageal junction cancer.
Study Details
In the double-blind trial, 780 patients from 197 sites in 30 countries were randomized between June 2013 and January 2016 to receive pertuzumab plus trastuzumab and chemotherapy (n = 388) or placebo plus trastuzumab and chemotherapy (control group, n = 392). Overall, 47% of patients were from Japan or other Asian countries. Treatment consisted of pertuzumab 840 mg or placebo every 3 weeks with trastuzumab (8 mg/kg loading dose, then 6 mg/kg every 3 weeks) plus chemotherapy with cisplatin 80 mg/m² every 3 weeks, oral capecitabine 1,000 mg/m² twice a day for 28 doses every 3 weeks, or 5-fluorouracil 800 mg/m² every 24 hours (120-hour continuous infusion) every 3 weeks.
The primary endpoint was overall survival in the intent-to-treat population.
Overall Survival
Median follow-up was approximately 25 months. At cutoff for the primary analysis—after 242 deaths in the pertuzumab group and 262 deaths in the control group—median overall survival was 17.5 months in the pertuzumab group vs 14.2 months in the control group (hazard ratio [HR] = 0.84, P = .057). Hazard ratios for overall survival were consistent across patient subgroups.
Median progression-free survival (8.5 vs 7.0 months, HR = 0.73, P = .0001) and objective response rate (56.7% vs 48.3%, P = .026) were better in the pertuzumab group; however, these analyses are descriptive only due to hierarchical testing and since the primary endpoint was not met. Additional anticancer therapy after study treatment was received by 43% of the pertuzumab group and 42% of the control group.
Adverse Events
The most common grade ≥ 3 adverse events were neutropenia (30% of the pertuzumab group vs28% of the control group), anemia (15% vs 17%), and diarrhea (13% vs 6%). Serious adverse events occurred in 45% vs 39% of patients, with diarrhea being the most common in both groups (4% vs 5%). Treatment-related deaths occurred in none of the patients in the pertuzumab group and in 7 patients in the control group.
The investigators concluded, “Adding pertuzumab to trastuzumab and chemotherapy did not significantly improve overall survival in patients with HER2-positive metastatic gastric or gastro-oesophageal junction cancer compared with placebo. Further studies are needed to identify improved first-line treatment options in these types of cancer and to identify patients with HER2-driven tumours who might benefit from dual HER2-targeted therapy.”
The study was funded by F. Hoffmann-La Roche Ltd.
Yoon-Koo Kang, MD, of Asan Medical Center, University of Ulsan College of Medicine, is the corresponding author for The Lancet Oncology article.
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