In an interview with Targeted Oncology, Ken Kato, MD, PhD, discussed background and findings from the phase 3 CheckMate 648 trial among patients with esophageal squamous cell carcinoma.
The phase 3 CheckMate 648 trial (NCT03143153) trial of nivolumab (Opdivo) and ipilimumab (Yervoy) led to overall survival (OS) benefits among patients with esophageal squamous cell carcinoma (ESCC).
At a median follow-up of 28.8 months, patients on nivolumab and chemotherapy (n = 321) had a median OS of 12.8 months (95% CI, 11.1-15.7) compared with 10.7 months (95% CI, 9.4-12.1) among patients who were given chemotherapy alone (n = 324). At 24 months, the OS rate favored the combination vs chemotherapy alone at 29% vs 19%, respectively.
OS was significantly longer for patients with a PD-L1 expression of 1% or greater on ipilimumab/nivolumab compared with those on chemotherapy alone at a median of 13.7 vs 9.1 months, respectively (HR, 0.64; 98.6% CI, 0.46-0.90; P = .001).
Additionally, the OS benefit was consistent across most subgroups in both the intention-to-treat (ITT) and PD-L1–positive populations. Patients in the ITT population assigned given the immunotherapy doublet (n = 325) had a median OS of 12.7 months (95% CI, 11.3-15.5) vs 10.7 months (95% CI, 9.4-12.1) for those assigned to chemotherapy alone (n = 324; HR, 0.77; 95% CI, 0.65-0.92).
For PD-L1–positive patients, those assigned to the doublet had a median OS of 13.1 months (95% CI, 11.2-17.4; n = 158) vs 9.1 (95% CI, 7.7-10.0) for those assigned to chemotherapy (n = 157; HR, 0.62; 95% CI, 0.48-0.80). Moreover, the OS at 24 months was 32% vs 19% in favor of the doublet in the ITT population, and 34% vs 12% in favor of the doublet in the PD-L1-positive population.
This global, randomized, open-label phase 3 CheckMate-648 trial enrolled patients with unresectable advanced, recurrent, or metastatic ESCC who had an ECOG performance status of 0 or 1 and measurable disease. Patients were randomly assigned to receive nivolumab at 240 mg every 2 weeks plus fluorouracil and cisplatin every 4 weeks, nivolumab at 3 mg/kg every 2 weeks plus ipilimumab at 1 mg/kg every 6 weeks, or fluorouracil plus cisplatin every 4 weeks.
In an interview with Targeted OncologyTM, Ken Kato, MD, PhD, chief of the department of head and neck, and esophageal medical oncology and gastrointestinal medical oncology at the National Cancer Center Hospital in Tokyo, Japan, discussed background and findings from the phase 3 CheckMate 648 trial among patients with ESCC.
Targeted Oncology: Can you provide an overview of the CheckMate 648 study?
Kato: The CheckMate 648 phase 3 trial compared the first-line chemotherapy in patients with esophageal squamous cell carcinoma to 5 FU plus nivolumab and ipilimumab plus nivolumab. At the ASCO GI meeting, the updated results with a longer follow-up [were presented] compared with the former data which were published in the New England Journal of Medicine.
What was the background of the study? What led to the start of this trial?
Esophageal squamous cell carcinoma has a very poor prognosis and there have not been chemotherapy options for decades. After the approval of nivolumab and pembrolizumab, we have more options for [patients]. So, we conducted the phase 3 trials, comparing nivolumab plus fluorouracil and cisplatin, nivolumab plus ipilimumab, or fluorouracil plus cisplatin.
What are the recent findings from the trial?
The primary result of the CheckMate 648 trial was already published and showed that treatment with nivolumab plus ipilimumab showed survival benefits over chemotherapy alone, which were statistically significant. These long-term follow-up data focus on the changing of the hazard ratio and the efficacy of the 2 treated arms of nivolumab plus fluorouracil and cisplatin or ipilimumab and nivolumab, compared with chemotherapy. We found consistent efficacy of the ipilimumab/nivolumab and the chemotherapy/nivolumab compared to the chemotherapy, and there is no added toxicity, even after the long-term follow-up.
What are the next steps for this research?
We found the better response with [ipilimumab and nivolumab] and with longer follow-up, compared with the chemotherapy/nivolumab. We should focus on the patient who achieved a long-term efficacy [result] with ipilimumab and nivolumab.
Last year, [we] presented [that for the] patient, [there is] already a benefit with ipilimumab/nivolumab. I think that a patient with a less aggressive disease with a small tumor burden, a good performance status, and good nutritional status, can be a good candidate for the ipilimumab/nivolumab treatment. Of course, the PD-L1 positivity is good and the predictive marker for the ipilimumab/nivolumab treatment, which we already [have seen] in the real-world data with ipilimumab/nivolumab and the patient background in the further evaluation.
Further combinations with an oral tyrosine kinase inhibitor or another targeted inhibitor are warranted in further investigation.