This is the first checkpoint inhibitor to show a statistically significant extension in OS for patients with PD-L1–unselected, unresectable advanced or recurrent esophageal cancer, announced Ono Pharmaceutical and Bristol-Myers Squibb (BMS), who collaborated on ATTRACTION-3 with the PD-1 inhibitor. Results of the study will be presented at an upcoming medical meeting.
Approximately 570,000 new cases are diagnosed with esophageal cancer worldwide annually and approximately 510,000 deaths from the disease each year. There are currently no effective second-line treatments for patients who progress on cisplatin and 5-fluorouracil, Ono Pharmaceutical stated in a press release.
In the international, multicenter, open-label, randomized ATTRACTION-3 trial, approximately 390 patients with esophageal cancer who were refractory to or intolerant of 1 prior combination therapy with fluoropyrimidine and platinum-based treatment received either nivolumab at 240 mg/body solution intravenously (IV) every 2 weeks or chemotherapy with docetaxel or paclitaxel until disease progression or severe adverse events (AEs). Docetaxel was administered at 75 mg/m2 IV every 2 weeks and paclitaxel at 100 mg/m2 weekly for 6 weeks followed by a 2-week treatment holiday.
The primary endpoint was OS; secondary endpoints were progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and safety.
To be eligible for enrollment, patients must have been ≥20 years of age, be refractory to or intolerant of standard therapy, have an ECOG performance score of 0 or 1, and a life expectancy of at least 3 months. Those with a current or past history of severe hypersensitivity to any other antibody products, multiple primary cancers, with symptomatic brain or meninx metastases, and active or suspected autoimmune disease were excluded.
Two-year findings from the open-label phase II ATTRACTION-01/ONO-4538-07 trial were presented at the 2017 ESMO Congress.2 In the trial, 65 patients with esophageal squamous cell carcinoma received nivolumab at 3 mg/kg IV every 2 weeks until progression or unacceptable toxicity. The primary endpoint was ORR evaluated by an independent review committee; secondary endpoints were OS, safety, PFS, and DOR.
Preliminary results showed that the ORR was 17.2% (95% CI, 9.9%-28.2%) as of May 17, 2015. With the 2-year update, the ORR was 17.2% and the median DOR was 11.7 months. Kaplan-Meier estimates for 1-, 1.5-, and 2-year OS rates were 45.3%, 25.0%, and 17.2%, respectively. One-, 1.5, and 2-year PFS rates were 10.3%, 8.6%, and 8.6%, respectively.
Regarding safety, grade 3/4 AEs were reported in 29.2% of patients (n = 19). The most common AEs were diarrhea (21.5%), decreased appetite (18.5%), lung infection (13.8%), and cough (12.3%). A total 7 patients discontinued nivolumab due to treatment-related AEs, and no treatment-related deaths were reported.
History and Future Development
In 2011, Ono Pharmaceutical granted BMS territorial rights to develop and commercialize nivolumab worldwide except in Japan, South Korea and Taiwan, which is where ONO retained all rights to nivolumab except the United States at the time. In July 2014, Ono and BMS expanded the collaboration agreement to jointly develop and commercialize multiple immunotherapies alone and in combination for patients with cancer in Japan, South Korea and Taiwan.
In addition, Ono Pharmaceutical is currently conducting a clinical development program that includes esophageal cancer, gastroesophageal junction cancer, small cell lung cancer, hepatocellular carcinoma, glioblastoma, urothelial cancer, ovarian cancer, and biliary tract cancer.
- Opdivo® (Nivolumab) Demonstrates a Significant Extension in Overall Survival Versus Chemotherapy in Patients with Unresectable Advanced or Recurrent Esophageal Cancer in Phase III Clinical Study. ONO Pharmaceutical Co., LTD. Published January 10, 2019. https://bit.ly/2D2P3bX?rel=0" . Accessed January 10, 2019.
- Kitagawa Y, Doki Y, Kato K, et al. Two year survival and safety update for esophageal squamous cell carcinoma treated with nivolumab (ATTRACTION-01/ONO-4538-07). Ann Oncol. 2017;28(5):mdx369.022. doi: 10.1093/annonc/mdx369.022.