189MO - Perioperative durvalumab in addition to neoadjuvant chemotherapy in patients with stage IIIa(N2) non-small cell lung cancer: Final analysis of the trial SAKK 16/14

Background

In the trial SAKK 16/14 perioperative durvalumab showed favorable outcomes for patients (pts) with resectable stage IIIA(N2) non-small cell lung cancer (NSCLC). This has been confirmed in randomized trials.

Methods

This multicenter, single-arm phase II trial investigated the benefit of perioperative treatment with durvalumab in addition to neoadjuvant chemotherapy with cisplatin and docetaxel, followed by surgery in pts 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%. Here we present the final analysis with a median follow-up of 72 months.

Results

The trial met its primary endpoint, achieving a 1-year EFS of 73%. Of the 68 pts enrolled, 55 (82%) pts underwent surgery, with 51 (93%) achieving a R0 resection. As of September 2, 2024, 31 pts 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;

Conclusions

To the best of our knowledge, this is the largest prospective trial to date investigating perioperative immunotherapy in pts 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 using the same chemotherapy regimen, the addition of immunotherapy nearly doubled the 5-year EFS and OS rate. It was particularly impressive in pts who achieved a MPR or pCR. The currently recruiting trial SAKK 16/18 is further exploring the potential benefit of immune-modulatory radiotherapy targeting the primary tumor. Clinical trial identification: NCT02572843.

Editorial acknowledgement

I acknowledge that no external support was used in writing the abstract. The abstract has been reviewed and accepted by all co-authors.

Legal entity responsible for the study

Swiss Group for Clinical Cancer Research (SAKK).

Funding

Swiss State Secretary for Education, Research and Innovation (SERI), Swiss Cancer Research Foundation (SCS), and Swiss Cancer League (SCL). Research funding for translational research projects was granted by Gateway for Cancer Research and Rising Tide Foundation. AstraZeneca provided drug and financial support.

Disclosure

S.I. Rothschild: Financial Interests, Institutional, Advisory Board: Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, MSD, Merck Serono, Novartis, Otsuka, Pfizer, PharmaMar, Roche Pharma, Sanofi Aventis, Takeda; Financial Interests, Institutional, Expert Testimony: Amgen, AstraZeneca, Bristol Myers Squibb, Janssen; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Bristol Myers Squibb, MSD, Pfizer, Roche Diagnostics, Roche Pharma, Takeda, Roche Pharma; Financial Interests, Institutional, Member of Board of Directors: Swiss Group for Clinical Cancer Research; Financial Interests, Personal, Research Grant: Roche Pharma; Financial Interests, Personal, Invited Speaker: AstraZeneca; Non-Financial Interests, Personal, Other, Elected Member of the Federal Drug Commission: Drug Commission Federal Office of Public Health, Switzerland. A. Zippelius: Financial Interests, Institutional, Advisory Board: Roche, BMS, Boehringer Ingelheim, MSD; Financial Interests, Institutional, Research Grant: Secarna, Roche, AstraZeneca, Beyondsprings, Brightpeaks, Catalym, T3. S. Savic Prince: Financial Interests, Institutional, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Pfizer; Financial Interests, Institutional, Advisory Board: Boehringer Ingelheim, Merck & Co. Inc. M. Frueh: Financial Interests, Institutional, Advisory Board: BMS, MSD, AstraZeneca, Boehringer Ingelheim, Roche, Takeda, Pfizer, Janssen, Daiichi Sankyo, PharmaMar. C. Britschgi: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Merck KGaA, Sanofi, Boehringer Ingelheim, Takeda, PharmaMar; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Amgen, MSD Oncology; Financial Interests, Personal and Institutional, Research Grant, Unrestricted Research Grant for translational research laboratory: Bayer. L.A. Mauti: Financial Interests, Personal, Advisory Board: Merck, Sanofi, Novartis, AstraZeneca, MSD, Pfizer, Regeneron, BMS, Roche, Janssen, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca. S. Peters: Financial Interests, Institutional, Advisory Board: Vaccibody, Takeda, Seattle Genetics, Sanofi, Roche/Genentech, Regeneron, Phosplatin Therapeutics, PharmaMar, Pfizer, Novartis, Mirati, Merck Serono, MSD, Janssen, Incyte, Illumina, IQVIA, GSK, Gilead, Genzyme, Foundation Medicine, F-Star, Eli Lilly, Debiopharm, Daiichi Sankyo, Boehringer Ingelheim, Blueprint Medicines, Biocartis, Bio Invent, BeiGene, Bayer, BMS, AstraZeneca, Arcus, Amgen, AbbVie, iTheos, Novocure; Financial Interests, Institutional, Invited Speaker: Takeda, Sanofi, Roche/Genentech, RTP, Pfizer, PRIME, PER, Novartis, Medscape, MSD, Imedex, Illumina, Fishawack, Eli Lilly, Ecancer, Boehringer Ingelheim, BMS, AstraZeneca, OncologyEducation, RMEI, Mirati; Financial Interests, Personal, Other, Associate Editor Annals of Oncology and Deputy Editor Lung Cancer: Elsevier; Financial Interests, Institutional, Advisory Board, Permanent independent scientific advisor: Hutchmed; Financial Interests, Institutional, Member of Board of Directors, Swiss network of pharmacies: Galenica; Financial Interests, Institutional, Invited Speaker, MERMAID-1: AstraZeneca; Financial Interests, Institutional, Invited Speaker, MERMAID-2, POSEIDON, MYSTIC: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering committee CheckMate 743, CheckMate 73L, CheckMate 331 and 451: BMS; Financial Interests, Institutional, Invited Speaker, RELATIVITY 095: BMS; Financial Interests, Institutional, Invited Speaker, BGB-A317-A1217-301/AdvanTIG-301: BeiGene; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair ZEAL-1: GSK; Financial Interests, Institutional, Invited Speaker, Clinical Trial steering Committee PEARLS, MK-7684A: MSD; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering Committee SAPPHIRE: Mirati; Financial Interests, Institutional, Invited Speaker, LAGOON: PharmaMar; Financial Interests, Institutional, Invited Speaker, phase 1/2 trials: Phosplatin Therapeutics; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair Skyscraper-01; chair ALEX; steering committee BFAST; steering committee BEAT-Meso; steering committee ImPower-030, IMforte: Roche/Genentech; Financial Interests, Institutional, Invited Speaker, Phase 2 Inupadenant with chemo: iTeos; Non-Financial Interests, Personal, Officer, ESMO President 2020–2022: ESMO; Non-Financial Interests, Personal, Officer, Council Member & Scientific Committee Chair: ETOP/IBCSG Partners; Non-Financial Interests, Personal, Officer, Vice-President Lung Group: SAKK; Non-Financial Interests, Personal, Other, Involved in Swiss politics: Swiss Political Activities; Non-Financial Interests, Personal, Officer, President and Council Member: Ballet Béjart Lausanne Foundation; Non-Financial Interests, Personal, Principal Investigator, Involved in academic trials: ETOP/EORTC/SAKK; Non-Financial Interests, Personal, Member: Association of Swiss Physicians FMH (CH), ASCO, AACR, IASLC; Non-Financial Interests, Personal, Leadership Role, ESMO President: ESMO; Non-Financial Interests, Personal, Member, Vice-President Lung Group: SAKK; Non-Financial Interests, Personal, Leadership Role, Vice-President: SAMO; Non-Financial Interests, Personal, Member, Association of Swiss interns and residents: ASMAC/VSAO. M.T. Mark: Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, Janssen, Roche, Takeda; Financial Interests, Personal, Expert Testimony: BMS. P.R. Froesch: Financial Interests, Personal, Advisory Board: Roche, Takeda, Sanofi, BMS; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Institutional, Advisory Board: MSD. All other authors have declared no conflicts of interest.