Patients With Advanced Esophageal Cancer Can Skip Chemo With Upfront Dual Immunotherapy Combo

Both single and dual immunotherapy regimens improve overall survival compared with chemotherapy in select patients with advanced esophageal squamous-cell carcinoma (ESCC), particularly in PD-L1-positive patients, according to data from the CheckMate 648 trial.

"The clinically meaningful improvements in survival of these two treatment regimens highlight immunotherapy's impact on cancer care and should bring new therapeutic options to a group of patients that are often diagnosed when disease has already spread," lead researcher Dr. Ian Chau of Royal Marsden Hospital in Sutton, U.K., said in a statement from the American Society of Clinical Oncology (ASCO) virtual annual meeting.

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The CheckMate 648 trial enrolled 970 patients with previously untreated, unresectable advanced, recurrent or metastatic ESCC, regardless of tumor cell PD-L1 expression. Patients were randomly allocated to nivolumab and chemotherapy (5-fluorouracil and cisplatin); nivolumab and ipilimumab; or chemotherapy alone (control).

With a minimum follow-up of 13 months, overall survival (OS) was significantly better among all patients treated with either nivolumab plus chemotherapy or nivolumab plus ipilimumab (13.2 and 12.8 months, respectively) compared with chemotherapy alone (10.7 months).

OS was also significantly better among patients with PD-L1 expression of at least 1% who received nivolumab plus chemotherapy and nivolumab plus ipilimumab (15.4 and 13.7 months, respectively) compared to chemotherapy alone (9.1 months).

Progression-free survival (PFS) was also better with nivolumab plus chemotherapy than chemotherapy alone in patients with PD-L1 expression of at least 1%.

Adverse events and serious adverse events (grade 3+) were comparable between the three groups.

"Encouragingly, treatment-related deaths were low among all three groups of patients and similar," Dr. Chau said in his ASCO presentation.

"Based on the results of this study, nivolumab plus chemotherapy and nivolumab plus ipilimumab each represent a new potential first-line standard of care for patients with advanced esophageal squamous cell carcinoma," he concluded.

Weighing in on the results after the presentation, ASCO Chief Medical Officer Dr. Julie Gralow said, "To date, there have been very few treatment advancements for esophageal or upper GI cancers."

"The CheckMate 648 study found two regimens that improved overall survival beyond the current standard of care, which is chemo alone for recurrent or metastatic esophageal cancers, particularly those that express PD-L1, which was found in about half of the tumors," she noted.

"The addition of the PD1 immune-checkpoint inhibitor nivolumab to chemotherapy, as well as the combination of two immune checkpoint inhibitors without chemotherapy - nivolumab and ipilimumab, a CTLA-4 inhibitor - both significantly extended survival and should be considered superior treatments as first-line treatment of esophageal squamous cell carcinoma. This dual immunotherapy combination without chemo is the first chemo-free first-line treatment showing benefit for these patients," said Dr. Gralow.

The study was funded by Bristol Myers Squibb. Several authors have disclosed financial relationships with the company.

—Megan Brooks

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