As reported in the Journal of Clinical Oncology by Lorenzen et al, the phase II portion of the German-Swiss phase II/III DANTE/IKF-s633 trial showed promising results with the addition of atezolizumab to perioperative chemotherapy in patients with resectable esophagogastric cancer.
Study Details
In the phase II portion of the multicenter open-label trial, 295 patients with resectable disease (≥ cT2 or cN1) were randomly assigned between September 2018 and October 2020 to receive either:
- Four preoperative and four postoperative biweekly cycles of FLOT (docetaxel at 50 mg/m2, oxaliplatin at 85 mg/m2, leucovorin at 200 mg/m2, and fluorouracil at 2,600 mg/m2 as a 24-hour infusion, all on day 1) combined with atezolizumab at 840 mg every 2 weeks, followed by eight cycles of atezolizumab at 1,200 mg every 3 weeks (n = 146)
- Four preoperative and four postoperative cycles of FLOT alone (n = 149).
Overall, 8% of patients had tumors with microsatellite instability (MSI); 58% had a PD-L1 combined positive score (CPS) of ≥ 1 and 18% had a CPS of ≥ 10.
Key Findings
Surgical morbidity occurred in 45% of patients in the atezolizumab group vs 42% of those in the control group. Mortality at 60 days was 3% vs 2%. R0 resection rates were 96% vs 95%.
Greater proportions of patients in the atezolizumab group had tumor downstaging to ypT0 (23% vs 15%, P = .044), ypT0-T2 (61% vs 48%, P = .015), and ypN0 (68% vs 54%, P = .012).
Histopathologic complete regression rates—pathologic complete response or tumor regression grade 1a—were higher in the atezolizumab group (24% vs 15%, P = .032). Differences were more marked in the CPS ≥ 10 subgroup (33% vs 12%) and MSI subgroup (63% vs 27%). Differences in the CPS < 1 and ≥ 1 subgroups were similar to that in the overall population.
Serious adverse events occurred in 69% vs 66% of patients. The most common grade 3 or 4 adverse events in both groups were neutropenia (45% vs 42%), leukopenia (13% vs 11%), and diarrhea (13% vs 8%). Treatment-related death occurred in one patient in the atezolizumab group (due to sepsis) and two patients in the control group (due to sepsis and pneumonia).
The investigators concluded, “Within the limitations of the exploratory nature of the data, the addition of atezolizumab to perioperative FLOT is safe and improved postoperative stage and histopathologic regression [in this patient population].”
Salah-Eddin Al-Batran, MD, of the Frankfurter Institut für Klinische Krebsforschung IKF and Krankenhaus Nordwest, UCT-University Cancer Center, Frankfurt, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Roche and H.W. & J. Hector Stiftung. For full disclosures of the study authors, visit ascopubs.org.
