Nivolumab Improves Survival in Advanced Esophageal Squamous-Cell Carcinoma

By Will Boggs MD

October 15, 2019

NEW YORK (Reuters Health) - Nivolumab boosts overall survival compared with chemotherapy in patients with advanced esophageal squamous-cell carcinoma (SCC) that's refractory or intolerant to previous chemotherapy, the ATTRACTION-3 trial shows.

Nivolumab, a human monoclonal anti-PD-1 antibody, is approved by the U.S. Food and Drug Administration (FDA) for the treatment of several solid tumors. The phase 2 ATTRACTION-1 study showed promising antitumor activity of nivolumab in patients with advanced esophageal SCC.

Dr. Ken Kato from National Cancer Center Hospital, in Tokyo, and colleagues in the open-label phase-3 ATTRACTION-3 compared nivolumab with chemotherapy (paclitaxel and docetaxel) in 419 patients with unresectable advanced or recurrent esophageal SCC who were refractory or intolerant to previous fluoropyrimidine-based and platinum-based chemotherapy.

Just under half of the patients in each group had tumors expressing at least 1% PD-L1 at baseline.

After a minimum follow-up of 17.6 months, median overall survival was significantly longer with nivolumab (10.9 months) than with chemotherapy (8.4 months), a 23% reduced risk of dying during the study period (P=0.019).

Median overall survival did not differ significantly according to tumor PD-L1 expression in either treatment group, the team writes in The Lancet Oncology, online September 30.

Objective response rates were similar in the nivolumab group (19%) and in the chemotherapy group (22%), but the median duration of response was substantially longer with nivolumab (6.9 months) than with chemotherapy (3.9 months).

Serious treatment-related adverse events were reported in 16% of nivolumab patients and in 23% of chemotherapy patients, with a similar incidence of treatment-related adverse events leading to discontinuation in both groups.

Quality of life was significantly and clinically meaningfully better with nivolumab treatment than with chemotherapy at all time points.

"Nivolumab might represent a new standard second-line treatment option for patients with advanced esophageal squamous cell carcinoma," the researchers conclude. "A phase 3 study assessing nivolumab-based regimens versus chemotherapy in first-line treatment of patients with esophageal squamous cell carcinoma is underway."

"Although ATTRACTION-3 potentially sets a new standard for previously treated patients with esophageal squamous cell carcinoma, the inclusion of few non-Asian participants might undermine the trial's global generalizability," write Dr. Elizabeth C. Smyth of the Cambridge University Hospitals NHS Foundation Trust, in Cambridge, U.K., and Dr. Florian Lordick of University Hospital Leipzig, in Germany, in a linked editorial.

"Subgroup analysis of the more global KEYNOTE-181 trial (of pembrolizumab) suggests anti-PD-1 therapy is more effective in Asian patients with esophageal squamous cell carcinoma than in non-Asian patients," they note. "Determining whether tumor or host factors, including ethnicity or region of origin, have precedence in response to immune checkpoint blockade in esophageal cancer will be crucial for future trial design and from a regulatory perspective."

"In future," the editorial concludes, "it is possible that perioperative immunotherapy or combinations of immunotherapy and chemotherapy or chemoradiation might ultimately improve long-term survival in patients with early and locally advanced esophageal squamous cell carcinoma."

ONO Pharmaceutical and Bristol-Myers Squibb funded the study, employed two authors and had various financial ties to several others, including the authors of the editorial.

SOURCE: https://bit.ly/328p6Sj and https://bit.ly/2ODoArq

Lancet Oncol 2019.

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