Meeting NewsPerspective

Nivolumab extends OS in advanced esophageal squamous cell carcinoma

BARCELONA, Spain — Nivolumab extended survival compared with chemotherapy among patients with advanced or recurrent esophageal squamous cell carcinoma regardless of PD-L1 expression, according to results of the randomized phase 3 ATTRACTION study presented at European Society for Medical Oncology Congress.

Nivolumab (Opdivo, Bristol-Myers Squibb) — a PD-1 immune checkpoint inhibitor — also appeared safe for this population.

“Nivolumab is the first immune checkpoint inhibitor to demonstrate a statistically significant and clinically meaningful improvement in OS vs. chemotherapy in previously treated advanced esophageal squamous cell carcinoma,” Byoung Chul Cho, MD, PhD, clinical oncologist at Yonsei Cancer Center at Yonsei University College of Medicine in South Korea, said during a presentation. “[This] represents a potential new standard second-line treatment option for [these patients].”

Chemotherapy often provides little benefit for patients with advanced esophageal squamous cell carcinoma.

The ATTRACTION study included 419 patients with unresectable, advanced or recurrent disease refractory to or intolerant of one prior treatment of fluoropyrimidine/platinum-based chemotherapy.

Researchers randomly assigned patients to nivolumab dosed at 240 mg every 2 weeks (n = 210) or investigator’s choice of chemotherapy with paclitaxel or docetaxel (n = 209) as second-line treatment.

OS served as the primary endpoint. Minimum follow-up was 17.6 months.

Results showed a statistically significant improvement in median OS for patients who received nivolumab (10.9 months vs. 8.4 months; HR = 0.77; 95% CI, 0.62-0.96).

A higher percentage of nivolumab-treated patients remained alive at 12 months (47% vs. 34%) and 18 months (31% vs. 21%).

Researchers observed the OS benefit with nivolumab among patients with PD-L1 expression of 1% or greater (HR = 0.69; 95% CI, 0.51-0.94), as well as those with expression below 1% (HR = 0.84; 95% CI, 0.62 to 1.14).

Overall response rates were comparable between groups (33% with nivolumab vs. 34% with chemotherapy). However, nivolumab-treated patients also achieved longer median duration of response (6.9 months vs. 3.9 months).

Patients assigned chemotherapy achieved longer median PFS (3.4 months vs. 1.7 months), but nivolumab-treated patients were more likely to be alive and progression free at 6 months (24% vs. 17%) and 12 months (12% vs. 7%).

A higher percentage of patients assigned chemotherapy experienced treatment-related adverse events (95% vs. 66%), grade 3/grade 4 adverse events (63% vs. 18%), or serious adverse events (23% vs. 16%). Nine percent of patients in each treatment group discontinued therapy due to adverse events.

Investigators reported statistically significant improvements in quality of life with nivolumab compared with chemotherapy through week 42, both with the EQ-5D visual analog scale (least square mean, 6.9; 95% CI, 3-10.9) and the EQ-5D utility index (least square mean, 0.076; 95% CI, 0.011-0.142).

“Today is an important day for our patients, who have been eagerly waiting for an effective therapy,” Cho said. “We are very proud to present this good news and hope nivolumab will bring change to these patients.” – by John DeRosier

Reference:

Cho BC, et al. Abstract LBA11. Presented at: European Society for Medical Oncology; Sept. 27-Oct. 1, 2019; Barcelona, Spain.

Disclosure s : Ono Pharmaceutical Co. and Bristol-Myers Squibb funded this study.

Cho reports honoraria from, consultant roles with or research funding from AstraZeneca, Bayer Champions Oncology, Bristol-Myers Squibb, Dizal Pharma, Dong-A, Eli Lilly, Janssen, Merck Sharpe & Dohme, Mogam Institute, Novartis, Ono Pharmaceutical Co., Pfizer, Roche, Takeda and Yuhan. He also reports stock ownership in Champions Oncology and TheraCanVac. Please see the abstract for all other authors’ relevant financial disclosures.

BARCELONA, Spain — Nivolumab extended survival compared with chemotherapy among patients with advanced or recurrent esophageal squamous cell carcinoma regardless of PD-L1 expression, according to results of the randomized phase 3 ATTRACTION study presented at European Society for Medical Oncology Congress.

Nivolumab (Opdivo, Bristol-Myers Squibb) — a PD-1 immune checkpoint inhibitor — also appeared safe for this population.

“Nivolumab is the first immune checkpoint inhibitor to demonstrate a statistically significant and clinically meaningful improvement in OS vs. chemotherapy in previously treated advanced esophageal squamous cell carcinoma,” Byoung Chul Cho, MD, PhD, clinical oncologist at Yonsei Cancer Center at Yonsei University College of Medicine in South Korea, said during a presentation. “[This] represents a potential new standard second-line treatment option for [these patients].”

Chemotherapy often provides little benefit for patients with advanced esophageal squamous cell carcinoma.

The ATTRACTION study included 419 patients with unresectable, advanced or recurrent disease refractory to or intolerant of one prior treatment of fluoropyrimidine/platinum-based chemotherapy.

Researchers randomly assigned patients to nivolumab dosed at 240 mg every 2 weeks (n = 210) or investigator’s choice of chemotherapy with paclitaxel or docetaxel (n = 209) as second-line treatment.

OS served as the primary endpoint. Minimum follow-up was 17.6 months.

Results showed a statistically significant improvement in median OS for patients who received nivolumab (10.9 months vs. 8.4 months; HR = 0.77; 95% CI, 0.62-0.96).

A higher percentage of nivolumab-treated patients remained alive at 12 months (47% vs. 34%) and 18 months (31% vs. 21%).

Researchers observed the OS benefit with nivolumab among patients with PD-L1 expression of 1% or greater (HR = 0.69; 95% CI, 0.51-0.94), as well as those with expression below 1% (HR = 0.84; 95% CI, 0.62 to 1.14).

Overall response rates were comparable between groups (33% with nivolumab vs. 34% with chemotherapy). However, nivolumab-treated patients also achieved longer median duration of response (6.9 months vs. 3.9 months).

Patients assigned chemotherapy achieved longer median PFS (3.4 months vs. 1.7 months), but nivolumab-treated patients were more likely to be alive and progression free at 6 months (24% vs. 17%) and 12 months (12% vs. 7%).

A higher percentage of patients assigned chemotherapy experienced treatment-related adverse events (95% vs. 66%), grade 3/grade 4 adverse events (63% vs. 18%), or serious adverse events (23% vs. 16%). Nine percent of patients in each treatment group discontinued therapy due to adverse events.

Investigators reported statistically significant improvements in quality of life with nivolumab compared with chemotherapy through week 42, both with the EQ-5D visual analog scale (least square mean, 6.9; 95% CI, 3-10.9) and the EQ-5D utility index (least square mean, 0.076; 95% CI, 0.011-0.142).

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“Today is an important day for our patients, who have been eagerly waiting for an effective therapy,” Cho said. “We are very proud to present this good news and hope nivolumab will bring change to these patients.” – by John DeRosier

Reference:

Cho BC, et al. Abstract LBA11. Presented at: European Society for Medical Oncology; Sept. 27-Oct. 1, 2019; Barcelona, Spain.

Disclosure s : Ono Pharmaceutical Co. and Bristol-Myers Squibb funded this study.

Cho reports honoraria from, consultant roles with or research funding from AstraZeneca, Bayer Champions Oncology, Bristol-Myers Squibb, Dizal Pharma, Dong-A, Eli Lilly, Janssen, Merck Sharpe & Dohme, Mogam Institute, Novartis, Ono Pharmaceutical Co., Pfizer, Roche, Takeda and Yuhan. He also reports stock ownership in Champions Oncology and TheraCanVac. Please see the abstract for all other authors’ relevant financial disclosures.

    Perspective

    This is the first randomized phase 3 study to look at nivolumab in this setting for advanced esophageal squamous cell carcinoma, and for that we must congratulate the researchers.

    There are external studies that help corroborate this finding. For example, if you put this study side-by-side with the KEYNOTE-181 study that looked at squamous cell carcinoma, you see that there are almost identical number of patients randomly assigned and you have a PD-L1 antibody vs. chemotherapy. The HR in that study was 0.78. In this one, you have an HR of 0.77, so the results are almost identical.

    But did nivolumab really make these patients feel better? They actually showed a significant improvement in quality of life, which is not normally seen in a trial this big. The clinically meaningful change in quality of life is 7 points, which is significantly better between nivolumab and chemotherapy.

    To put it all together, we see that nivolumab induces similar response rates to taxanes. We do not see a significant difference in PFS, but there was a significant improvement in OS and quality of life with nivolumab. Based on this, I would say that treatment of squamous cell cancer in the esophagus will be platinum-based chemotherapy in the first-line setting, and we really need to think about using a PD-1 antibody in the second-line setting. Chemotherapy will probably have to be used in a later line.

    Most importantly, we have shown that a PD-1 antibody works in squamous cell cancer of the esophagus, and we really look forward to first-line data from many studies that are recruiting right now to compare these drugs with chemotherapy.

    • Ian Chau, MD, FRCP
    • The Royal Marsden NHS Foundation Trust

    Disclosures: HemOnc Today could not confirm relevant financial disclosures.

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