Nivolumab shows promise for esophageal cancer

Nivolumab appeared safe and effective in the treatment of patients with esophageal cancer, according to results of a phase 2 clinical trial.

“The central assessment with RECIST showed that 17% of patients had an objective response and 42% achieved disease control, which suggests that the ability of nivolumab to reduce tumor burden in esophageal squamous cell carcinoma is long lasting, similar to the findings in other cancer types,” Toshihiro Kudo, PhD, from Frontier Science for Cancer and Chemotherapy at Osaka University Graduate School of Medicine in Osaka, Japan, and colleagues wrote.

Nivolumab (Opdivo, Bristol-Myers Squibb) — a PD-1 inhibitor — has produced durable responses against multiple malignancies by inhibiting the binding of PD-L1 and PD-L2 to PD-1 and regulating the balance of T-cell activation. It is approved for the treatment of advanced squamous and nonsquamous non–small cell lung cancers, melanoma and Hodgkin lymphoma.
Researchers also are exploring the efficacy of nivolumab in other cancers, including gastrointestinal cancer.

Kudo and colleagues enrolled 65 patients (median age, 62 years; range, 49-80) with advanced squamous cell carcinoma, adenosquamous cell carcinoma or adenocarcinoma of the esophagus from eight academic centers and hospitals in Japan. All patients were refractory or intolerant to fluoropyrimidine-based, platinum-based and taxane-based chemotherapy.

Patients received 3 mg/kg IV nivolumab in a 60-minute infusion once every 2 weeks across 6-week cycles for a median of three cycles (range, 1-10).

Centrally assessed objective response — the number of patients with a complete or partial best response — served as the primary endpoint.

Median follow-up was 10.8 months (interquartile range, 4.9-14.3).

The central and investigator-assessed analyses included 64 patients.

Researchers reported rates of partial or complete response of 17% (n = 11; 95% CI, 10-28) by central assessment and 22% (n = 14; 95% CI, 14-33) by investigator assessment.

Disease control rates included 42% (n = 27; 95% CI, 31-54) by central assessment and 53% (n = 34; 95% CI, 41-65) by investigator assessment.

Forty-three deaths and 54 PFS events occurred by cutoff. Median OS was 10.8 months (95% CI, 7.4-13.3). The median duration of centrally assessed PFS was 1.5 months (95% CI, 1.4-2.8) and investigator assessed PFS was 2.3 months (95% CI, 1.5-3).

The most common grade 4 adverse events included dyspnea and hyponatremia (2%). Grade 3 events included lung infection (8%), as well as decreased appetite, increased blood creatinine phosphokinase and dehydration (3% for each).

Serious adverse events included lung infection (6%), dehydration (3%) and interstitial lung disease (3%), among others.

Researchers attributed no deaths to treatment.

The safety profile and activity of nivolumab in this patient population shows that immune-checkpoint inhibitors have promise for the treatment of various digestive cancers, Sylvain Manfredi, MD, and Antoine Drouillard, MD from the hepato-gastroenterology and digestive oncology department at University Hospital Dijon in France, wrote in a related editorial.

“The results of Kudo and colleagues suggest promising future opportunities for the palliative management of esophageal cancer,” they wrote. “Confirmation in a phase 3 randomized controlled trial that compared nivolumab alone or in combination with chemotherapy, with standard chemotherapy is needed.” – by Melinda Stevens

Disclosures: Kudo reports research grants from Chugai, Ono Pharmaceutical and Yakult Honsya. Please see the full study for a list of all other researchers’ relevant financial disclosures. Drouillard and Manfredi report no relevant financial disclosures.