1237MO - 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

Background

For patients with resectable stage IIIA(N2) non-small cell lung cancer (NSCLC) neoadjuvant chemotherapy with 3 cycles cisplatin (cis)/docetaxel (doce) followed by surgery is an accepted standard of care achieving a 1-year event-free survival (EFS) of 48%. PD-(L)1 inhibitors have recently shown high response rates in resectable NSCLC.

Methods

Neoadjuvant treatment consisted of 3 cycles of cis 100 mg/m² and doce 85 mg/m² q3w followed by 2 cycles of durvalumab 750 mg q2w. Durvalumab was continued after surgery for 1 year. The primary endpoint is EFS at 1 year. The hypothesis for statistical considerations was an improvement of EFS at 1 year from 48% to 65%.

Results

Sixty-eight patients were included. Radiographic response rate was 44.8% (95%CI: 32.6-57.4) after neoadjuvant chemotherapy (CR: 4.5%, PR: 40.3%, SD: 44.8%) and 58.1% (95%CI: 44.8-70.5) after additional neoadjuvant immunotherapy (CR: 6.5%, PR: 51.6%, SD: 25.8%). Of the 55 resected patients, 10 patients (18.2%) had a pathological complete response and 33 patients (60.0%) a major pathological response defined as ≤10% viable tumor cells by central pathology review. Postoperative nodal down-staging was observed in 37 patients (67.3%). 1-year EFS was 73.3% (90%CI: 60.1-82.7). At the time of the analysis, median EFS was not reached. After a median follow up of 28 months, median OS was not reached. Thirteen patients had died with disease progression/disease recurrence as the most frequent reason (11 patients). 59 patients (88.1%) had an AE grade ≥3 including two fatal cases (one postoperative bleeding complication and one respiratory failure). Results for PD-L1 expression and tumor mutational burden will be presented during the meeting.

Conclusions

This is to our knowledge the largest study of patients with resectable stage IIIA(N2) NSCLC investigating perioperative immune checkpoint inhibitor therapy. The addition of perioperative durvalumab to standard of care cis/doce is safe and results in a encouraging 1-year EFS rate exceeding historical data of chemotherapy alone and achieves a high major pathological response rate.

Clinical trial identification

NCT02572843.

Editorial acknowledgement

Legal entity responsible for the study

Swiss Group for Clinical Cancer Research SAKK.

Funding

Foundation or academic group WITH funding from a pharma, biotech, or other commercial company - AstraZeneca.

Disclosure

S.I. Rothschild: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): BMS; Advisory/Consultancy, Research grant/Funding (institution): Merck Serono; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Eisai; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis; Honoraria (institution), Advisory/Consultancy: Roche; Advisory/Consultancy: Takeda. A. Zippelius: Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy: MSD; Advisory/Consultancy: BMS; Research grant/Funding (institution): Beyondsprings; Research grant/Funding (institution): Secarna; Research grant/Funding (institution): Crescendo. S. Savic Prince: Advisory/Consultancy: MSD; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Roche; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Thermo Fisher Scientific. D. Betticher: Advisory/Consultancy: MSD; Advisory/Consultancy: Roche; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Janssen-Cilag; Advisory/Consultancy: Novartis. M. Früh: Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Roche; Advisory/Consultancy: Takeda. M. Joerger: Non-remunerated activity/ies: ESMO Press & Media Affairs Committee. C. Britschgi: Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Takeda; Advisory/Consultancy: Janssen-Cilag; Advisory/Consultancy: Boehringer Ingelheim. S. Peters: Advisory/Consultancy: AbbVie; Advisory/Consultancy: Amgen; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Bayer; Advisory/Consultancy: Biocartis; Advisory/Consultancy: Bioinvent; Advisory/Consultancy: Blueprint Medicines; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy, Research grant/Funding (institution): Clovis; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Debiopharm; Honoraria (institution), Advisory/Consultancy: Eli Lilly; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): F. Hoffmann-La Roche; Advisory/Consultancy: Foundation Medicine; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Illumina; Advisory/Consultancy: Janssen; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy, Research grant/Funding (institution): Merck Serono; Advisory/Consultancy: Merrimack; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Pharma Mar; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Regeneron; Honoraria (institution), Advisory/Consultancy: Sanofi; Advisory/Consultancy: Seattle Genetics; Honoraria (institution), Advisory/Consultancy: Takeda; Advisory/Consultancy: Vaccibody; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Biodesix. M.T. Mark: Advisory/Consultancy: BMS; Advisory/Consultancy: Roche; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: MSD; Advisory/Consultancy: Takeda. W. Janthur: Honoraria (self), Advisory/Consultancy: Roche; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Takeda; Honoraria (self), Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis. P.R. Froesch: Advisory/Consultancy: Roche; Advisory/Consultancy: Takeda; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: BMS; Advisory/Consultancy: Pfizer. M. Pless: Advisory/Consultancy: Abbvie; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer Ingelheim; Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Advisory/Consultancy: Eisai; Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche; Advisory/Consultancy: Takeda; Advisory/Consultancy: MSD; Travel/Accommodation/Expenses: Vifor; Honoraria (institution): Janssen-Cilag.