SAKK 16/14: Anti-PD-L1 antibody durvalumab in addition to neoadjuvant chemotherapy in patients with stage IIIA(N2) non-small cell lung cancer (NSCLC)—A multicenter single-arm phase II trial.

Abstract

9016 Background: For patients (pts) with resectable stage IIIA(N2) non-small cell lung cancer (NSCLC) neoadjuvant chemotherapy (chemo) with 3 cycles cisplatin (cis)/docetaxel (doc) followed by surgery is an accepted standard of care leading to a 1-year (yr) event-free survival (EFS) of 48% and a 5-yr overall survival (OS) of 37%. PD-1/PD-L1 inhibitors have recently shown to lead to high response rates in resectable NSCLC. Methods: SAKK 16/14 is an open-label single-arm phase II study including 68 pts with resectable NSCLC stage IIIA(N2) (T1-3 N2 M0), irrespective of histological subtype, genomic aberrations or PD-L1 expression status. Neoadjuvant treatment consisted of 3 cycles of cis 100 mg/m2 and doc 85 mg/m2 q3w followed by 2 cycles of durvalumab 750 mg q2w. Durvalumab was continued after surgery q2w for 1 yr. The primary endpoint is EFS at 1 yr. The statistical hypothesis is to improve EFS at 1 yr from 48% based on the SAKK 16/00 study to 65%. Here, we report the primary endpoint and response data from 67 evaluable pts included in the study. Results: 68 pts were included from 06/16 to 01/19 and 67 pts (35 males, 32 females) were evaluable. Median age was 61 yrs (range, 41-74). 52 pts (77.6%) had a WHO PS of 0. 95.5% were current or former smokers. The majority of tumors were adenocarcinoma (55.2%) followed by squamous cell histology (32.8%). Clinical stage T1, T2 and T3 were present at diagnosis in 22.4%, 49.3% and 28.4%, respectively. 81.1% of pts underwent resection. The main reason for not undergoing surgery was disease progression (33.3%). Pneumonectomy was performed in 5 pts (9.1%), 43 pts underwent lobectomy and 7 pts bilobectomy. 30-day postoperative mortality was observed in one patient (1.8%). One patient died due to a bleeding complication after surgery most likely not related to neoadjuvant therapy. Radiographic response was 44.8% (95%CI: 32.6-57.4) after neoadjuvant chemo and 59.7% (95%CI: 46.4-71.9) after additional neoadjuvant immunotherapy. 1-yr EFS was 73.3% (90%CI: 62.5-81.4). Results for pathologic remission rate as well as correlation with PD-L1 status will be presented during the meeting. Conclusions: We report on treatment outcomes of the largest cohort of pts with resectable stage IIIA(N2) NSCLC receiving perioperative immune checkpoint inhibitor therapy. The addition of perioperative durvalumab to standard of care cis/doc is safe and leads to a high response rate and a very encouraging 1-yr EFS rate that appears substantially higher than with chemo alone. Clinical trial information: NCT 02572843.

Navigating Diagnostic and Treatment Decisions in Non-Small Cell Lung Cancer: Expert Commentary on the Multidisciplinary Team Approach

“…In an exploratory trial of patients with stage IIIA resectable NSCLC treated with platinum‐based CTx plus nivolumab before undergoing surgery ( n = 13), the overall response rate was approximately 85%, with 9 patients (69.2%) achieving complete pathological response (95% CI, 38.6–90.9%) [66]. The SAKK 16/14 trial demonstrated a 1‐year event‐free survival rate of 73.3% with CTx and durvalumab, followed by surgery and 12 months of postoperative durvalumab, in patients with resectable stage IIIA NSCLC [67]. The TOP 1501 trial features patients with stage IB, II, or IIIA NSCLC being treated with neoadjuvant pembrolizumab monotherapy, followed by postoperative CTx and pembrolizumab [7].…”

Current state and prospect of the perioperative strategy for non-small cell lung cancer

“…In the same year, previous results from the NEOSTAR study (28), a preoperative phase II study of nivolumab plus ipilimumab, and results from the MK3475-223 study (29), a phase I study of pembrolizumab, were reported, both of which had similar safety and MPR values of 20-30%. Other Phase II and Ib studies of various drugs (atezolizumab and durvalumab, an anti-PD-L1 antibody, and sintilimab, a recently emerging anti-PD-1 antibody) in combination with chemotherapy have been reported, all of which have shown similar results (30)(31)(32).…”

Surgery after Induction Targeted Therapy and Immunotherapy for Lung Cancer

“…Immunotherapy in combination with chemotherapy was found to be safe in the neoadjuvant setting. The one-year event-free survival rate was 73.3% [ 34 ].…”