Adjuvant durvalumab administered after trimodality therapy appeared safe for patients with locally advanced esophageal and gastroesophageal junction adenocarcinoma, according to study results presented at Gastrointestinal Cancers Symposium.
The regimen also demonstrated encouraging activity, according to researchers.
Concurrent chemoradiation followed by esophagectomy is the standard treatment for locally advanced esophageal adenocarcinoma.
Approximately one-third of patients achieve pathologic complete response to this treatment; however, approximately half of the patients who do not achieve pathologic complete response relapse within a year, according to study background.
No adjuvant therapies have demonstrated a survival benefit for these patients. However, immune checkpoint inhibitors appear active among patients with metastatic, , and preclinical studies have shown upregulation of the PD-1 pathway among patients who underwent radiation with or without chemotherapy.
Hirva Mamdani, PhD, of the division of hematology-oncology at Indiana University, and colleagues conducted a phase 2 study to assess the safety and efficacy of durvalumab (Imfinzi, AstraZeneca) — a PD-L1 inhibitor — for patients with locally advanced esophageal and gastroesophageal junction adenocarcinoma who did not achieve pathologic complete response after neoadjuvant chemoradiation and R0 resection.
The analysis included 24 patients (median age, 60 years; range, 43-74), of whom 10 had distal esophageal adenocarcinoma and 14 had gastroesophageal adenocarcinoma.
Eighteen patients had received carboplatin plus paclitaxel, and six had received cisplatin and 5-FU. Patients received chemotherapy concurrently with radiation (50 Gy to 50.4 Gy).
Nineteen patients (79%) had positive lymph nodes at the time of surgery after neoadjuvant chemoradiation therapy; of these, three (12.5%) had N3 disease, nine (37.5%) had N2 disease and seven (29%) had N1 disease.
Among the five patients with no positive nodes, two had T3N0 disease, one had T2N0 disease and two had T1N0 disease.
All patients received durvalumab 1,500 mg via IV every 4 weeks for up to 1 year after surgery.
One-year RFS served as the primary endpoint. Secondary endpoints included incidence and severity of treatment-related adverse events.
Median follow-up was 11.7 months (range, 1.7-23.9).
By this time, seven patients (29%) had relapsed; five remained alive at the time of analysis.
Seventeen patients (67%) remained disease free; of these, six remained on treatment, seven completed treatment and three were off treatment.
Researchers reported 1-year RFS of 78.6%, higher than the historical rate of 50%.
Mamdani and colleagues projected a 26-month RFS rate of 62.9%.
Five patients developed grade 3 adverse events. These included one case each of diarrhea, hepatitis, encephalopathy, hyperglycemia and hypoglycemia.
The most common grade 1 and grade 2 adverse events included fatigue (33.3%), nausea (25%) and cough (20.8%). – by Mark Leiser
For more information:
Mamdani H, et al. Abstract 5. Presented at: Gastrointestinal Cancers Symposium; Jan. 17-19, 2019; San Francisco.
Disclosure: Mamdani reports a consultant/advisory role with Tempus. Please see the abstract for all other authors’ relevant financial disclosures.