Atezolizumab After Chemoradiotherapy Elicits Promising Responses in ESCC
In the phase 2 EPOCI1802 trial, atezolizumab monotherapy elicited a cCR rate of 42.1%, an ORR of 65.8%, and a 12-month OS rate of 65.8% in advanced ESCC.
In the phase 2 EPOCI1802 trial, atezolizumab monotherapy elicited a cCR rate of 42.1%, an ORR of 65.8%, and a 12-month OS rate of 65.8% in advanced ESCC.
Atezolizumab (Tecentriq) monotherapy administered after platinum-based definitive chemoradiotherapy elicited promising responses in patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC), according to data from the phase 2 EPOCI1802 trial (UMIN000034373) published in Nature Cancer.1
Among the first consecutive 38 patients, the confirmed complete response (cCR) rate was 42.1% (95% CI, 28.5%-56.7%), and in the exploratory cohort (n = 10), the cCR was 50.0% (95% CI, 18.7%-81.3%). The overall response rate (ORR) in the primary analysis population was 65.8% (95% CI, 48.6%-80.4%) vs 80.0% (95% CI, 44.4%-97.5%) in the exploratory cohort.
The median progression-free survival (PFS) was 3.2 months, and the 12-month PFS rate was 29.6%. The median overall survival (OS) was 31.0 months, and the 12-month OS rate was 65.8%.
“In conclusion, atezolizumab monotherapy following [platinum-based definitive chemoradiotherapy] resulted in a promising cCR rate and may lead to long-term survival without additional safety outcomes,” senior study author Takashi Kojima, MD, of the Department of Gastroenterology and Gastrointestinal Oncology at National Cancer Center Hospital East in Kashiwa, Japan, and coauthors wrote in the paper.1
EPOCI1802 was a multicenter trial that enrolled a total of 40 patients who had unresectable locally advanced ESCC and received treatment with 2 cycles of cisplatin and fluorouracil and 60 Gy of radiation in the primary analysis. In this trial, patients received atezolizumab monotherapy every 3 weeks for a maximum of 12 months. Additionally, the trial enrolled an exploratory cohort that consisted of 10 patients with locoregionally recurrent ESCC after radical surgery because additional surgical resection is difficult, and they are not normally treated with platinum-based definitive chemoradiotherapy.
The median age of patients in the primary cohort was 64 years (range, 45-79), the majority were male (82.5%), had an ECOG performance status of 0 (80.0%), had stage IVA disease (72.5%), and had a primary lesion located in the middle region (65.0%).
Eligible patients had histologically confirmed primary ESCC, a primary lesion located in the thoracic esophagus, disease diagnosed as unresectable, no distant metastasis except supraclavicular lymph node, and no prior treatment for esophageal cancer except endoscopic resection before chemoradiotherapy.2 Additionally, patients were 20 years or older with an ECOG performance status of 0 or 1, a life expectancy of 3 months or longer, and adequate hematologic and organ function.
Patients with active double cancers, past or concurrent inflammatory bowel disease, past or concurrent interstitial lung disease, poorly controlled diabetes mellitus, or history of cardiovascular risk were excluded from trial participation.
The trial’s primary end point was cCR rate. Secondary end points were cCR rate per investigator’s assessment in the exploratory cohort, cCR rate determined by central assessment, ORR, and incidence of adverse events (AEs).
Of the patients who underwent platinum-based definitive chemoradiotherapy in the primary cohort (n = 51), the cCR rate was 35.3%. In patients who achieved a cCR, the median PFS was not reached, and the 12-month PFS rate was 67.5%. For patients who had a PD-L1 tumor proportion score (TPS) of less than 1%, the cCR rate was 44.4% compared with 41.2% in patients with a PD-L1 TPS of 1% or greater, which was not a significant difference.
Additionally, 23 of 40 patients (57.5%) discontinued atezolizumab because of disease progression, and 11 of 40 patients (27.5%) completed the atezolizumab monotherapy regimen. In the exploratory cohort, 6 of 10 patients (60.0%) discontinued atezolizumab due to progression. The median relative dose intensity was 97.3% in the primary cohort and 95.6% in the exploratory cohort.
Regarding safety, 5.0% and 10.0% of the primary and exploratory cohorts, respectively, experienced grade 3 or higher pneumonitis; 3 patients experienced grade 1/2 hypothyroidism, 1 experienced grade 2 adrenal insufficiency, and 1 experienced grade 1 hyperthyroidism in the primary cohort. There were no treatment-related deaths.
The study authors expressed that further results confirming the survival benefits from platinum-based definitive chemoradiotherapy and atezolizumab from the phase 3 SKYSCRAPER-07 trial (NCT04543617) are “essential”.
References
- Bando H, Kumagai S, Kotani D, et al. Atezolizumab following definitive chemoradiotherapy in patients with unresectable locally advanced esophageal squamous cell carcinoma – a multicenter phase 2 trial (EPOC1802). Nat Cancer. Published February 19, 2025. doi:10.1038/s43018-025-00918-1
- A phase II, multicenter study to investigate the safety and efficacy of atezolizumab monotherapy as a sequential therapy following chemoradiotherapy in patients with locally advanced unresectable esophageal cancer. UMIN-CTR. Updated June 16, 2023. Accessed March 12, 2025. https://tinyurl.com/53a54hm9
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