Opdivo-Based Regimens Approved as First-Line Treatments for Esophageal Cancer

The Food and Drug Administration (FDA) has approved Opdivo^® (nivolumab) in combination with fluoropyrimidine- and platinum-containing chemotherapy and Opdivo^® plus Yervoy^® (ipilimumab), as first-line treatments for adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC) regardless of PD-L1 status.

The approvals are based on data from the randomized, active-controlled, open-label phase 3 CheckMate-648 trial (ClinicalTrials.gov Identifier: NCT03143153), which included 970 adults with previously untreated unresectable advanced, recurrent or metastatic ESCC. Patients were randomly assigned 1:1:1 to receive 1 of the following treatments: Opdivo plus chemotherapy (fluorouracil and cisplatin); Opdivo plus Yervoy, or chemotherapy alone.

The coprimary endpoints were overall survival (OS) and progression-free survival (PFS) in patients whose tumor cells expressed PD-L1 of at least 1% (TC PD-L1 ≥1%). Key secondary endpoints were OS and PFS in all randomized patients.

Results showed that treatment with Opdivo plus chemotherapy was associated with superior OS vs chemotherapy alone, both in the TC PD-L1 ≥1% population (hazard ratio [HR], 0.54; 95% CI, 0.41-0.71; P <.0001), and in all randomized patients (HR, 0.74; 95% CI, 0.61-0.90; P =.0021).

In the TC PD-L1 ≥1% population, the median OS was 15.4 months (95% CI, 11.9-19.5) for Opdivo plus chemotherapy vs 9.1 months (95% CI, 7.7-10) with chemotherapy alone. In all randomized patients, the median OS was 13.2 months (95% CI, 11.1-15.7) for Opdivo plus chemotherapy vs 10.7 months (95% CI, 9.4-11.9) for chemotherapy alone. 

Additionally, in the TC PD-L1 ≥1% population, median PFS was reported to be 6.9 months (95% CI, 5.7-8.3) for Opdivo plus chemotherapy and 4.4 months (95% CI, 2.9-5.8) for chemotherapy alone (HR 0.65; 95% CI, 0.49-0.86, P =.0023). In all randomized patients, Opdivo plus chemotherapy did not meet statistical significance for PFS.

Treatment with Opdivo plus Yervoy also demonstrated superior OS vs chemotherapy alone, in the TC PD-L1 ≥1% population (HR, 0.64; 95% CI, 0.49-0.84; P =.001) and in all randomized patients (HR, 0.78; 95% CI, 0.65-0.95; P =.011).

In the TC PD-L1 ≥1% population, the median OS was 13.7 months (95% CI, 11.2-17.0) for Opdivo plus Yervoy vs 9.1 months (95% CI, 7.7-10) for chemotherapy alone. In all randomized patients, the median OS was 12.8 months (95% CI, 11.3-15.5) for Opdivo plus Yervoy vs 10.7 months (95% CI, 9.4-11.9) for chemotherapy alone. Opdivo plus Yervoy did not meet statistical significance for PFS in the TC PD-L1 ≥1% population and therefore was not hierarchically tested in the total population.

“Today brings welcome news for many advanced or metastatic esophageal squamous cell carcinoma patients and oncologists,” said Jaffer A. Ajani, MD, CheckMate-648 co-first author and lead US investigator, and professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center. “In the CheckMate-648 trial, two nivolumab-based combinations showed a survival benefit compared to chemotherapy alone, offering new treatment options regardless of PD-L1 status.”

Opdivo-based regimens are now approved for 5 indications in upper gastroesophageal cancers.

References

1. US Food and Drug Administration approves two Opdivo^® (nivolumab)-based regimens as first-line treatments for unresectable advanced or metastatic esophageal squamous cell carcinoma. News release. Bristol Myers Squibb. May 27, 2022. Accessed May 31, 2022. https://www.businesswire.com/news/home/20220524006181/en/U.S.-Food-and-Drug-Administration-Approves-Two-Opdivo%C2%AE-nivolumab–Based-Regimens-as-First-Line-Treatments-for-Unresectable-Advanced-or-Metastatic-Esophageal-Squamous-Cell-Carcinoma
2. Opdivo. Package insert. Bristol Myers Squibb; 2022. Accessed May 31, 2022. https://packageinserts.bms.com/pi/pi_opdivo.pdf