Session

Oral presentation clinical solid tumor oncology

Nov. 20, 2024, 1:45 p.m. - 3:15 p.m., Kairo 1-2

Abstract

Perioperative Durvalumab in Addition to Neoadjuvant Chemotherapy in Patients With Stage IIIA(N2) Non–Small-Cell Lung Cancer – Final analysis of the multicenter single-arm phase II trial SAKK 16/14

S. I. Rothschild^{1, 2}, A. Zippelius², S. Hayoz³, S. Chiquet³, S. Savic Prince², A. Bettini⁴, M. Frueh⁵, M. Joerger⁵, D. Lardinois², H. Gelpke⁶, I. Opitz⁷, C. Britschgi^{7, 6}, L. A. Mauti⁶, S. Peters⁸, M. Mark⁹, R. Cathomas⁹, A. F. Ochsenbein³, W.-D. Janthur¹⁰, C. Waibel¹, N. Mach¹¹, P. Froesch¹², M. Buess², P. Bohanes⁸, M. Gonzalez⁸, M. Pless⁶, Presenter: S. I. Rothschild^{1, 2} (¹Baden, ²Basel, ³Bern, ⁴Fribourg, ⁵St. Gallen, ⁶Winterthur, ⁷Zurich, ⁸Lausanne, ⁹Chur, ¹⁰Aarau, ¹¹Geneva, ¹²Locarno)

Objective

In the trial SAKK 16/14 perioperative durvalumab showed favorable outcomes for patients with resectable stage IIIA(N2) non-small cell lung cancer (NSCLC). This has been confirmed in randomized trials. Here we present the final analysis with a median follow-up of 72 months.

Methods

This multicenter, single-arm phase II trial investigated the benefit of perioperative treatment with the anti-PD-L1 inhibitor durvalumab in addition to neoadjuvant chemotherapy with cisplatin and docetaxel, followed by surgery in patients with resectable stage IIIA (N2) NSCLC. Durvalumab was administered postoperatively for 1 year. The primary endpoint was event-free survival (EFS) at 1 year. The statistical hypothesis was based on an improvement in EFS at 1 year from 48% to 65%.

Results

The trial met its primary endpoint, achieving a 1-year EFS of 73%. Of the 68 patients enrolled, 55 (82%) patients underwent surgery, with 51 (93%) achieving a complete (R0) resection. As of September 2, 2024, 31 patients experienced an event (25 progressions, 3 second tumors and 3 deaths). The median EFS was 4.0 years [95% confidence interval (CI): 2.4 years-NR] and 5-year EFS rate was 45.9% [95% CI: 31.7 -59.0%]. By the time of analysis, 25 deaths had occurred. The median OS was not reached and estimated 5-year OS rate was 65.8% [95% CI: 52.9-76.0%]. A major pathologic response (MPR; <10% viable tumor cells) was observed in 34 patients (62%), and 10 patients (18%) achieved a pathologic complete response (pCR). Postoperative nodal downstaging (ypN0-1) was reported in 37 patients (67%). Notably, patients who achieved a pCR had a 5-year OS rate of 100% [95% CI NR-NR], and those patients with a MPR had a 5-year survival rate of 97% [95% CI NR-NR].

Conclusion

To the best of our knowledge, this is the largest prospective trial to date investigating perioperative immunotherapy in patients with resectable NSCLC, with a follow-up period of 6 years. When compared to a pooled analysis of previous trials conducted by our working group on resectable stage IIIA(N2) NSCLC using the same chemotherapy regimen, the addition of immunotherapy nearly doubled the 5-year EFS and OS rate. It was particularly impressive in patients who achieved a major or complete pathological response. The currently recruiting trial SAKK 16/18 is further exploring the potential benefit of immune-modulatory radiotherapy targeting the primary tumor.