FDA Grants 2 Frontline Nivolumab-Based Regimens Approval for Unresectable Advanced or Metastatic ESCC

Publication
Article
Oncology Nursing NewsAugust 2022
Volume 16
Issue 4

Nivolumab in combination with fluoropyrimidine- and platinum-containing chemotherapy and nivolumab plus ipilimumab received FDA approval as a first-line treatment for adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma, irrespective of PD-L1 status

Nivolumab (Opdivo) in combination with fluoropyrimidine- and platinum-containing chemotherapy and nivolumab plus ipilimumab (Yervoy) received FDA approval as a first-line treatment for adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma, irrespective of PD-L1 status.1

The regulatory decision is based on data from the phase 3 CheckMate-648 trial (NCT03143153), in which nivolumab plus chemotherapy or ipilimumab significantly improved overall survival (OS) vs chemotherapy alone in the all-randomized population and in the subset of patients with a PD-L1 expression of 1% or higher.2

In the all-randomized population, the median OS with nivolumab plus chemotherapy was 13.2 months (95% CI, 11.1-15.7) vs 10.7 months (95% CI, 9.4-11.9) with chemotherapy alone, translating to a 39% reduction in the risk of death (HR, 0.74; 95% CI, 0.61-0.90; P = .0021). The median PFS was 5.8 months (95% CI, 5.6-7.0) and 5.6 months (95% CI, 4.3-5.9), respectively (HR, 0.81; 95% CI, 0.67-0.99; P = not significant).

In the subset of patients with a PD-L1 expression of 1% or higher, the median OS with nivolumab/chemotherapy was 15.4 months (95% CI, 11.9-19.5) vs 9.1 months (95% CI, 7.7-10) with chemotherapy alone, translating to a 46% reduction in the risk of death (HR, 0.54; 95% CI, 0.41-0.71; P < .0001). The median PFS in the investigative and control arms was 6.9 months (95% CI, 5.7-8.3) and 4.4 months (95% CI, 2.9-5.8), respectively (HR, 0.63; 95% CI, 0.49-0.86; P = .0023).

The dual immunotherapy combination comprised of nivolumab and ipilimumab resulted in a median OS of 13.7 months (95% CI, 11.2-17.0) vs 9.1 months (95% CI, 7.7-10) with chemotherapy alone in the subset of patients with a PD-L1 expression of 1% or higher, translating to a 36% reduction in the risk of death (HR, 0.64; 95% CI, 0.49-0.84; P = .0010). In the all-randomized population, the median OS was 12.8 months (95% CI, 11.3-15.5) with the immunotherapy regimen vs 10.7 months (95% CI, 9.4-11.9) with chemotherapy alone, translating to a reduction in the risk of death by 22% (HR, 0.78; 95% CI, 0.65-0.95; P = .0110).

Moreover, in the subset with a PD-L1 expression of 1% or higher, the median PFS with nivolumab/ipilimumab was 4.0 months (95% CI, 2.4-4.9) vs 4.4 months (95% CI, 2.9-5.8) with chemotherapy alone (HR, 1.02; 95% CI, 0.78-1.34), failing to meet statistical significance. Because it was not significant, it was not hierarchically tested in the all-randomized population.

“Today brings welcome news for many advanced or metastatic esophageal squamous cell carcinoma patients and oncologists,” Jaffer A. Ajani, MD, lead investigator of CheckMate-648, and professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center, stated in a press release. “Unresectable advanced or metastatic ESCC is a challenging disease, and there’s a need for additional treatment options that may extend survival in the first-line setting. 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.”

Patients with unresectable advanced, recurrent, or metastatic ESCC were enrolled to the global, randomized, open-label phase 3 CheckMate-648 trial. They were required to have an ECOG performance status of 0 or 1 and measurable disease. Notably, they could not have received prior systemic therapy for advanced disease.

Study participants (n = 970) were randomized 1:1:1 to receive nivolumab at 240 mg every 2 weeks plus fluorouracil and cisplatin every 4 weeks (n = 321), nivolumab at 3 mg/kg every 2 weeks plus ipilimumab at 1 mg/kg every 6 weeks (n = 325), or fluorouracil plus cisplatin every 4 weeks (n = 324).

Stratification factors included PD-L1 tumor cell expression (≥1% vs ≤1%), region (East Asia vs rest of Asia vs rest of the world), performance status (0 vs 1), and number of organs with metastases (≤1 vs ≥2).

The primary end points of the trial included OS and PFS in the subset of patients with a PD-L1 expression of 1% or higher, and key secondary end points include OS and PFS in the all-randomized population and objective response rate (ORR) in both populations.

At a data cutoff of January 18, 2021, the minimum follow-up was 12.9 months. Additional data presented during the 2021 ASCO Annual Meeting indicated that the combination of nivolumab and chemotherapy elicited an ORR of 53% (95% CI, 45%-61%) in the subset of patients with a PD-L1 expression of 1% or higher vs 20% (95% CI, 14%-27%) with chemotherapy alone. In the all-randomized population, these rates were 47% (95% CI, 42%-53%) and 27% (95% CI, 22%-32%), respectively.

The median duration of response (DOR) in the subset of patients with a PD-L1 expression of 1% or higher in the investigative and control arms was 8.4 months (95% CI, 6.9-12.4) and 5.7 months (95% CI, 4.4-8.7), respectively. In the all-randomized population, the median DOR was 8.2 months (95% CI, 6.9-9.7) and 7.1 months (95% CI, 5.7-8.2), respectively.

The dual immunotherapy combination produced an ORR of 35% (95% CI, 28%-43%) vs 20% (95% CI, 14%-27%) with chemotherapy alone in the subset of patients with a PD-L1 expression of 1% or higher. These rates were 28% (95% CI, 23%-33%) and 27% (95% CI, 22%-32%), respectively, in the all-randomized population.

The median DOR with nivolumab plus ipilimumab in the subset of patients with a PD-L1 expression of 1% or higher was 11.8 months (95% CI, 7.1-27.4) vs 5.7 months (95% CI, 4.4-8.7) with chemotherapy alone. In all-randomized patients, the median DOR was 11.1 months (95% CI, 8.3-14.0) in the investigative arm and 7.1 months (95% CI, 5.7-8.2) in the control arm.

Nivolumab monotherapy and in combination with ipilimumab is linked with severe and fatal immune-mediated adverse reactions such as pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, nephritis and renal dysfunction, dermatologic adverse reactions, other immune-mediated adverse reactions.

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 27, 2022. https://bit.ly/3PMxNeb
  2. Chau I, Doki Y, Ajani JA, et al. Nivolumab (NIVO) plus ipilimumab (IPI) or NIVO plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced esophageal squamous cell carcinoma (ESCC): first results of the CheckMate 648 study. J Clin Oncol. 2021;39(suppl 15):LBA4001. doi:10.1200/JCO.2021.39.15_suppl.LBA4001
Related Videos
Karyn Goodman
Expert in oncology
Expert in oncology
Experts in oncology
Expert in oncology
Expert in oncology
Expert in oncology
Expert in oncology
Experts in oncology
Related Content
© 2023 MJH Life Sciences

All rights reserved.