There was a 37 percent reduced risk of death in patients with advanced gastric or gastroesophageal junction (GEJ) cancer who were treated with Opdivo (nivolumab) compared to placebo, following second or later-line chemotherapy, according to the findings from the phase 3 ONO-4538-12 trial presented at the 2017 Gastrointestinal Cancers Symposium.
In the double-blind study, which was conducted in Asia, the median overall survival (OS) was 5.32 months with Opdivo versus 4.14 months in the placebo arm. The six-month OS rate was 46.4 percent with Opdivo versus 34.7 percent for placebo and the 12-month OS rate was 26.6 percent with Opdivo compared with 10.9 percent in the placebo arm.
"This phase 3 study demonstrated the efficacy and safety of nivolumab as third or later line of treatment in patients with advanced gastric cancer," said lead study investigator Yoon-Koo Kang, M.D., Ph.D., Department of Oncology at the University of Ulsan College of Medicine, Asan Medical Center in Seoul, Korea. "These results indicate that nivolumab could be a new treatment option for patients with heavily pretreated advanced gastric cancer, and also provide a strong rationale to explore nivolumab in earlier lines of treatment for gastric cancer."
The phase 3 double-blind trial was conducted by Ono Pharmaceuticals, which is the company developing Opdivo in Japan, Korea and Taiwan. In the United States, the PD-1 inhibitor is developed and commercialized by Bristol-Myers Squibb. The primary endpoint of the study was OS, and secondary endpoints focused on progression-free survival (PFS) and objective response rate (ORR).
The trial randomized 493 patients with unresectable advanced or recurrent gastric or GEJ cancer in a 2-1 ratio to receive Opdivo (330 patients) or placebo (163 patients). Opdivo was administered at 3 mg/kg intravenously every two weeks. All patients had an ECOG performance status between 0 and 1, confirmed adenocarcinoma, and were at least 20 years of age. Those with brain metastasis requiring treatment were excluded.
Median PFS with Opdivo was 1.61 versus 1.45 months with placebo, representing a 40 percent reduction in the risk of progression or death. The 12-month PFS rates were 7.6 percent versus 1.5 percent, for Opdivo and placebo, respectively.
The ORR with Opdivo was 11.2 percent compared with 0 percent with placebo. The ORR consisted entirely of partial responses. The median duration of response for Opdivo was 9.53 months. Biomarker analyses from the study are still under way, according to Kang.
Treatment-related adverse events (AEs) of any grade were experienced by 42.7 percent of patients treated with Opdivo compared with 26.7 percent of those in the placebo arm. Grade 3/4 treatment-related AEs were noted in 10.3 percent and 4.3 percent of those in the Opdivo and placebo arms, respectively. The most commonly reported treatment-related grade 3/4 AEs with Opdivo were diarrhea, fatigue, decreased appetite, pyrexia and increases in AST and ALT. Discontinuation rates due to AEs were similar between the arms (2.7 percent vs 2.5 percent).
"OS was superior versus placebo, with long-term survival shown," said Kang. "Nivolumab had superior response rates, disease control, and PFS versus placebo, and was well tolerated with a safety profile comparable to the placebo arm."
Since its initial approval in 2014 for metastatic melanoma, Opdivo has added numerous indications across a variety of settings for patients with lung cancer, renal cell carcinoma, Hodgkin lymphoma and continued indications in combination with Yervoy (ipilimumab) for melanoma. Additionally, the treatment continues to be assessed across multiple types of cancer, including gastrointestinal malignancies.
“ONO-4538-12 is the first randomized, phase 3 Immuno-Oncology trial to demonstrate improved survival for patients with previously treated advanced or recurrent gastric cancer," Ian M. Waxman, M.D., development lead, Gastrointestinal Oncology, Bristol-Myers Squibb, said in a statement. "We find these results with Opdivo encouraging, as gastric cancer is a leading cause of cancer death globally and unmet needs remain for patients with advanced forms of this disease who become intolerant to chemotherapy or for whom such treatment has failed.”