Adjuvant durvalumab prolongs RFS in oesophageal adenocarcinoma
Adjuvant treatment with durvalumab, a PD-L1 inhibitor, following trimodality therapy may improve relapse-free survival (RFS) in patients with locally advanced oesophageal adenocarcinoma (LA-EAC) or gastroesophageal junction (GEJ) adenocarcinoma who did not achieve pCR* after neoadjuvant chemoradiation, according to a small study presented at the ASCO Gastrointestinal Cancers Symposium 2019 (ASCO GI 2019).
“Patients who did not achieve a pCR and have persistent disease in the lymph nodes are at a higher risk of relapse [within the first year after surgery] … and no adjuvant therapy has been shown to improve survival in these patients,” said study lead author Dr Hirva Mamdani from Karmanos Cancer Institute/Wayne State University in Detroit, Michigan, US.
“[The] safety profile of durvalumab … and efficacy results are very encouraging in this high-risk patient population [that demonstrated an increased] 1-year RFS,” she added.
Using data from the Big Ten Cancer Research Consortium study, Mamdani and colleagues conducted a multicentre, phase II trial involving 24 patients (median age, 60 years), of whom 10 had distal EAC and 14 had GEJ adenocarcinoma. Participants were given concurrent carboplatin/paclitaxel (n=18) or cisplatin/5-fluorouracil (n=6) with up to 13 doses of intravenous adjuvant durvalumab (1,500 mg every 4 weeks for 12 months). The adjuvant durvalumab therapy was started within 1–3 months of surgery and patients were followed up for 1 year. [ASCO GI 2019, abstract 5]
At a median follow-up of 14.5 months, patients who received adjuvant durvalumab demonstrated a 1-year RFS rate of 79.2 percent, “[which was higher] compared with a historical [RFS] rate of 50 percent,” Mamdani noted.
A 26-month RFS rate of approximately 68 percent was projected in patients treated with durvalumab.
Twelve patients discontinued treatment due to disease relapse, adverse events (AEs), and study withdrawal. The most common grade 3–4 AEs reported were pneumonitis (n=1), hepatitis (n=1), and colitis (n=1), which all leads to treatment discontinuation.
Fatigue and nausea were the most common treatment-related AEs, with 25 percent of patients experiencing grade 1 fatigue or nausea and 8.3 percent of patients experiencing grade 2 fatigue.
One patient experienced grade 3 hypoglycaemia and hyperglycaemia but this was considered unrelated to treatment and did not lead to treatment discontinuation.
“Adjuvant durvalumab in patients who have residual disease, following trimodality therapy for LA-EAC and GEJ adenocarcinoma was feasible,” said Mamdani.
“This was such a small study, we just wanted to see if there is any signal of activity at all, and if there was, then we will basically look at the subgroups,” Mamdani noted.
“Our next step is to expand our study further to enrol more patients and hopefully do a randomized trial,” she said.
*pCR: Pathologic complete response