Clinical Pearls & Morning Reports
Doki et al. conducted CheckMate 648, a global phase 3 trial that evaluated the efficacy and safety of nivolumab plus chemotherapy and nivolumab plus ipilimumab in previously untreated patients with advanced esophageal squamous-cell carcinoma. Read the NEJM Original Article here.
Q: What is the prognosis for advanced esophageal squamous-cell carcinoma with existing therapies?
A: Esophageal cancer causes more than half a million cancer-related deaths worldwide each year, with squamous-cell carcinoma accounting for approximately 85% of cases. Many esophageal cancers are unresectable at diagnosis, and most patients treated with curative intent eventually have a relapse. First-line chemotherapy for advanced esophageal squamous-cell carcinoma results in poor outcomes (median overall survival, <1 year).
Q: How common is tumor-cell programmed death ligand 1 (PD-L1) expression in esophageal squamous-cell carcinoma?
A: Tumor-cell PD-L1 expression in esophageal squamous-cell carcinoma is enriched, with expression of 1% or greater detected in approximately 50% of patients with advanced disease. Treatment with the anti–PD-1 mononuclear antibody nivolumab has been reported to result in significantly longer overall survival than chemotherapy in previously treated patients with advanced esophageal squamous-cell carcinoma and is approved for this indication, irrespective of PD-L1 expression status.
A: In the CheckMate 648 trial, first-line treatment with nivolumab in combination with chemotherapy or as a chemotherapy-free combination with ipilimumab resulted in a significant overall survival benefit over chemotherapy alone in patients with advanced esophageal squamous-cell carcinoma. In both the overall population and among patients with tumor-cell PD-L1 expression of 1% or greater, the median overall survival exceeded 1 year, with patients surviving 2.0 to 6.3 months longer with a nivolumab-containing regimen than with chemotherapy alone. Nivolumab plus chemotherapy was also associated with significantly longer progression-free survival than chemotherapy alone among patients with tumor-cell PD-L1 expression of 1% or greater. Treatment with either nivolumab-based regimen resulted in a higher percentage of patients who had a complete response, as well as in more durable responses, than chemotherapy alone.
A: The safety profiles of nivolumab plus chemotherapy and nivolumab plus ipilimumab were consistent with the known profiles of the individual components at similar doses. Treatment with nivolumab plus ipilimumab primarily resulted in immune-mediated adverse events (the most common being rash, pruritus, and hypothyroidism) at frequencies expected with this combination. Although treatment-related serious adverse events were more common with the nivolumab-based regimens than with chemotherapy alone, treatment-related adverse events of grade 3 or 4 that had potential immunologic causes occurred in no more than 6% of the patients across the organ categories. The incidence of treatment-related deaths was similar across the three treatment groups and occurred in approximately 2% of the patients in each group.