“It will require bigger studies to sort out exactly how efficacious it is and where the best place to use it is going to be, but it’s exciting to have agents to explore,” she concluded.
The international randomized phase III trial, sponsored by Merrimack Pharmaceuticals, enrolled 417 patients with metastatic pancreatic cancer who had previously received gemcitabine-based therapy. They were randomized to receive the investigational agent MM-398 alone, 5-fluorouracil (5-FU) plus leucovorin (LV) alone, or the combination.
Intention-to-treat analysis showed that median overall survival was 4.2 months with 5-FU/LV alone but 6.1 months with MM-398 plus 5-FU/LV (hazard ratio, 0.57; P = .0009), Dr. Chen reported.
Findings were similar across subgroups and in the per-protocol population, defined as patients who received at least 80% of the dose intensity of the protocol-defined treatment during the first 6 weeks of treatment (8.9 vs. 5.1 months; hazard ratio, 0.47; P = .0018).
In addition, the MM-398 plus 5-FU/LV combination was associated with a better median progression-free survival (3.1 vs. 1.5 months, P = .0001), overall response rate (16% vs. 1%, P less than .001), and cancer antigen 19-9 (CA19-9) response rate (36% vs. 12%, P = .0009).
The combination did lead to higher rates of dose reductions and dose delays, but treatment discontinuations were generally similar at 11% with the combination and 8% with 5-FU/LV alone.
Patients in the combination group were more likely to experience various grade 3 or worse toxicities, such as fatigue (14% vs. 4%), diarrhea (13% vs. 5%), and a reduction in neutrophil count (20% vs. 2%).