The Food and Drug Administration (FDA) has approved Opdivo (nivolumab) in combination with fluoropyrimidine- and platinum-containing chemotherapy as well as 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 with PD-L1 expression levels of at least 1% (PD-L1 ≥1%). Key secondary endpoints were OS and PFS in all randomized patients.


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Results showed that treatment with Opdivo plus chemotherapy was associated with superior OS vs chemotherapy alone, both in the 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 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. 

In the PD-L1 ≥1% population, the median PFS was 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, there was no significant difference in PFS.

Treatment with Opdivo plus Yervoy also demonstrated superior OS vs chemotherapy alone in the 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 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 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 investigator and a professor at The University of Texas MD Anderson Cancer Center. “In the CheckMate-648 trial, 2 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

This article originally appeared on MPR