Adding perioperative durvalumab to neoadjuvant chemotherapy may improve outcomes in patients with stage IIIA(N2) non-small cell lung cancer (NSCLC), according to phase 2 results published in the Journal of Clinical Oncology.1
In the phase 3 SAKK 16/00 trial (ClinicalTrials.gov Identifier: NCT00030771), patients with stage IIIA(N2) NSCLC received neoadjuvant cisplatin and docetaxel followed by surgery, and the 1-year event-free survival (EFS) rate was 48%.2
In the phase 2 SAKK 14/16 trial (ClinicalTrials.gov Identifier: NCT02572843), researchers set out to determine if adding perioperative treatment with durvalumab would improve outcomes.
The SAKK 14/16 trial included 67 evaluable patients with NSCLC who had confirmed involvement of the N2 lymph nodes and a high risk of recurrence after surgery. The patients received 3 cycles of cisplatin and docetaxel once every 3 weeks, followed by 2 doses of durvalumab once every 2 weeks.
Patients went on to surgery 2 to 4 weeks after the last dose of durvalumab. Between 4 and 6 weeks after surgery, patients started adjuvant treatment with durvalumab, given once every 2 weeks for 26 cycles.
In all, 60 patients completed 3 cycles of neoadjuvant chemotherapy, 55 patients underwent resection, and 50 started adjuvant durvalumab. The median duration of adjuvant treatment was 52 weeks (range, 2-54 weeks).
After neoadjuvant chemotherapy, the objective response rate was 43% (29/67), with 2 patients achieving a complete response (CR). After neoadjuvant durvalumab, the objective response rate was 58% (36/62), with 4 patients achieving a CR.
The major pathologic response (MPR) rate was 62% (34/55), and the pathologic CR (pCR) rate was 18% (10/55).
Postoperative nodal downstaging to ypN1 was reported in 20% of patients (11/55), and ypN0 was observed in 47% (26/55). In all, 93% of patients had an R0 resection.
Patients with PD-L1 expression of 25% or higher had a higher rate of pCR (odds ratio, 4.8; 95% CI, 1.0-22.8; P =.047). However, there was no significant association between PD-L1 expression and MPR, nodal downstaging, or EFS at 1 year.
The 1-year EFS rate was 73%. At a median follow-up of 28.6 months, the median EFS and overall survival (OS) had not been reached. The OS rate was 91% at 1 year and 83% at 2 years.
In a post hoc analysis, the researchers found that patients with an MPR, a pCR, or nodal clearance had a longer median EFS. MPR was also associated with OS.
All 67 patients were included in the safety population, and all experienced at least 1 adverse event (AE). Grade 3 or higher AEs occurred in 88% of patients. There were 2 fatal AEs, but they were considered unrelated to treatment.
AEs of special interest related to durvalumab included pneumonitis (3%), hypersensitivity reactions (5%), and hepatic function abnormalities (10%).
“Our results support the addition of perioperative immune checkpoint inhibitors to neoadjuvant chemotherapy in patients with resectable stage IIIA(N2) NSCLC,” the study authors wrote. “The fact that the high pathologic remission rate is associated with overall outcome, which has also been shown in other trials, has implications for the design of future trials.”
Disclosures: This research was supported, in part, by AstraZeneca. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
- Rothschild SI, Zippelius A, Eboulet EI, et al. SAKK 16/14: Durvalumab in addition to neoadjuvant chemotherapy in patients with stage IIIA(N2) non–small-cell lung cancer—a multicenter single-arm phase II trial. J Clin Oncol. Published online July 12, 2021. doi:10.1200/JCO.21.00276
- Pless M, Stupp R, Ris H-B, et al. Induction chemoradiation in stage IIIA/N2 non-small-cell lung cancer: A phase 3 randomised trial. Lancet. 2015; 386(9998):1049-56. doi:10.1016/S0140-6736(15)60294-X