In a Swiss phase II trial (SAKK 16/14) reported in the Journal of Clinical Oncology, Rothschild et al found that the addition of perioperative durvalumab to neoadjuvant cisplatin/docetaxel resulted in a high major pathologic response rate and an event-free survival rate of 73% in patients with stage IIIA(N2) non–small cell lung cancer (NSCLC).
As stated by the investigators, “For patients with resectable stage IIIA(N2) NSCLC, neoadjuvant chemotherapy with cisplatin and docetaxel followed by surgery resulted in a 1-year event-free survival rate of 48% in the [Swiss cooperative group for Cancer Research] SAKK 16/00 trial and is an accepted standard of care. We investigated the additional benefit of perioperative treatment with durvalumab.”
Study Details
In the investigator-initiated multicenter trial, 67 patients enrolled between June 2016 and January 2019 received neoadjuvant therapy consisting of three cycles of cisplatin at 100 mg/m2 and docetaxel at 85 mg/m2 once every 3 weeks followed by two doses of durvalumab at 750 mg once every 2 weeks; durvalumab at the same dosage was continued for 1 year after surgery. The primary endpoint was 1-year event-free survival, with the hypothesis being an increase in rate from 48% to 65%.
Response Rates and Event-Free Survival
Radiographic response rates were 43% after neoadjuvant chemotherapy and 58% after sequential neoadjuvant immunotherapy. Among 55 patients undergoing resection, 34 (62%) had a major pathologic response (≤ 10% viable tumor cells) and 10 (18%) had a pathologic complete response. Postoperative nodal downstaging (ypN0-1) was observed in 37 patients (67%). R0 resection was achieved in 51 (93%) of resected patients. A total of 50 patients (75%) started adjuvant durvalumab.
Event-free survival at 1 year was 73% (90% confidence interval [CI] = 63%–82%). Median follow-up was 28.6 months. Median event-free survival was not reached, with a 2-year rate of 68%, and median overall survival was not reached, with 1- and 2-year rates of 91% and 83%.
Patients (n = 13) with PD-L1 expression in ≥ 25% of tumor cells were more likely to achieve pathologic complete response (odds ratio = 4.8, P = .047). No significant associations of PD-L1 expression with major pathologic response, nodal downstaging, or 1-year event-free survival were observed.
Adverse Events
Overall, grade ≥ 3 adverse events occurred in 88% of patients, including in 67% during neoadjuvant chemotherapy, in 13% during neoadjuvant immunotherapy, in 29% during the perioperative phase, and in 50% during adjuvant durvalumab. During neoadjuvant durvalumab treatment, the most common grade ≥ 3 treatment-related adverse events were increased alanine aminotransferase, dyspnea, fatigue, and lung infection (5% each); any-grade pneumonitis occurred in 3%, hypersensitivity reactions in 5%, and hepatic function abnormalities in 10%. Adverse events led to death in two patients, due to respiratory failure during neoadjuvant chemotherapy and to bronchopulmonary hemorrhage at 10 days after surgery; neither death was considered related to study medications.
The investigators concluded, “The addition of perioperative durvalumab to neoadjuvant chemotherapy in patients with stage IIIA(N2) NSCLC is safe and exceeds historical data of chemotherapy alone with a high major pathologic response rate and an encouraging 1-year event-free survival rate of 73%.”
Sacha I. Rothschild, MD, PhD, of the Department of Medical Oncology and Comprehensive Cancer Center, University Hospital Basel, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Swiss State Secretary for Education, Research and Innovation, Swiss Cancer Research Foundation, AstraZeneca, and others. For full disclosures of the study authors, visit ascopubs.org.
