Sacha I Rothschild1, Alfred Zippelius1, Eric I Eboulet2, Spasenija Savic Prince3, Daniel Betticher4, Adrienne Bettini4, Martin Früh5,6, Markus Joerger5, Didier Lardinois7, Hans Gelpke8, Laetitia A Mauti9, Christian Britschgi10, Walter Weder11, Solange Peters12, Michael Mark13, Richard Cathomas13, Adrian F Ochsenbein6, Wolf-Dieter Janthur14, Christine Waibel15, Nicolas Mach16, Patrizia Froesch17, Martin Buess18, Pierre Bohanes19, Gilles Godar2, Corinne Rusterholz2, Michel Gonzalez20, Miklos Pless9. 1. Department of Medical Oncology and Comprehensive Cancer Center, University Hospital Basel, Basel, Switzerland. 2. SAKK Coordinating Center, Bern, Switzerland. 3. Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland. 4. Department of Oncology, HFR Fribourg-Hôpital fribourgeois, Fribourg, Switzerland. 5. Department of Oncology/Hematology, Cantonal Hospital St Gallen, St Gallen, Switzerland. 6. Department of Oncology, Inselspital Bern, Bern, Switzerland. 7. Division of Thoracic Surgery, University Hospital Basel, Basel, Switzerland. 8. Department of Thoracic and Visceral Surgery, Cantonal Hospital Winterthur, Winterthur, Switzerland. 9. Department of Oncology, Cantonal Hospital Winterthur, Winterthur, Switzerland. 10. Department of Medical Oncology and Hematology, Comprehensive Cancer Center Zurich, University Hospital Zurich, University of Zurich, Zurich, Switzerland. 11. Department of Thoracic Surgery, University Hospital of Zurich, Zurich, Switzerland. 12. Department of Oncology, University Hospital Lausanne CHUV, Lausanne, Switzerland. 13. Divison of Oncology/Hematology, Cantonal Hospital Graubünden, Chur, Switzerland. 14. Department of Oncology/Hematology, Cantonal Hospital Aarau, Aarau, Switzerland. 15. Department of Oncology, Cantonal Hospital Baden, Baden, Switzerland. 16. Department of Oncology, University Hospital Geneva, Geneva, Switzerland. 17. Oncology Institute of Southern Switzerland, Bellinzona, Switzerland. 18. Division of Medical Oncology, St Claraspital, Basel, Switzerland. 19. Centre de Chimiothérapie Anti-Cancéreuse, Lausanne, Switzerland. 20. Department of Thoracic Surgery, University Hospital Lausanne CHUV, Lausanne, Switzerland.
Abstract
PURPOSE: For patients with resectable stage IIIA(N2) non-small-cell lung cancer, neoadjuvant chemotherapy with cisplatin and docetaxel followed by surgery resulted in a 1-year event-free survival (EFS) rate of 48% in the SAKK 16/00 trial and is an accepted standard of care. We investigated the additional benefit of perioperative treatment with durvalumab. METHODS: Neoadjuvant treatment consisted of three cycles of cisplatin 100 mg/m2 and docetaxel 85 mg/m2 once every 3 weeks followed by two doses of durvalumab 750 mg once every 2 weeks. Durvalumab was continued for 1 year after surgery. The primary end point was 1-year EFS. The hypothesis for statistical considerations was an improvement of 1-year EFS from 48% to 65%. RESULTS: Sixty-eight patients were enrolled, 67 were included in the full analysis set. Radiographic response rate was 43% (95% CI, 31 to 56) after neoadjuvant chemotherapy and 58% (95% CI, 45 to 71) after sequential neoadjuvant immunotherapy. Fifty-five patients were resected, of which 34 (62%) achieved a major pathologic response (MPR; ≤ 10% viable tumor cells) and 10 (18%) among them a complete pathologic response. Postoperative nodal downstaging (ypN0-1) was observed in 37 patients (67%). Fifty-one (93%) resected patients had an R0 resection. There was no significant effect of pretreatment PD-L1 expression on MPR or nodal downstaging. The 1-year EFS rate was 73% (two-sided 90% CI, 63 to 82). Median EFS and overall survival were not reached after 28.6 months of median follow-up. Fifty-nine (88%) patients had an adverse event grade ≥ 3 including two fatal adverse events that were judged not to be treatment-related. CONCLUSION: The addition of perioperative durvalumab to neoadjuvant chemotherapy in patients with stage IIIA(N2) non-small-cell lung cancer is safe and exceeds historical data of chemotherapy alone with a high MPR and an encouraging 1-year EFS rate of 73%.
PURPOSE: For patients with resectable stage IIIA(N2) non-small-cell lung cancer, neoadjuvant chemotherapy with cisplatin and docetaxel followed by surgery resulted in a 1-year event-free survival (EFS) rate of 48% in the SAKK 16/00 trial and is an accepted standard of care. We investigated the additional benefit of perioperative treatment with durvalumab. METHODS: Neoadjuvant treatment consisted of three cycles of cisplatin 100 mg/m2 and docetaxel 85 mg/m2 once every 3 weeks followed by two doses of durvalumab 750 mg once every 2 weeks. Durvalumab was continued for 1 year after surgery. The primary end point was 1-year EFS. The hypothesis for statistical considerations was an improvement of 1-year EFS from 48% to 65%. RESULTS: Sixty-eight patients were enrolled, 67 were included in the full analysis set. Radiographic response rate was 43% (95% CI, 31 to 56) after neoadjuvant chemotherapy and 58% (95% CI, 45 to 71) after sequential neoadjuvant immunotherapy. Fifty-five patients were resected, of which 34 (62%) achieved a major pathologic response (MPR; ≤ 10% viable tumor cells) and 10 (18%) among them a complete pathologic response. Postoperative nodal downstaging (ypN0-1) was observed in 37 patients (67%). Fifty-one (93%) resected patients had an R0 resection. There was no significant effect of pretreatment PD-L1 expression on MPR or nodal downstaging. The 1-year EFS rate was 73% (two-sided 90% CI, 63 to 82). Median EFS and overall survival were not reached after 28.6 months of median follow-up. Fifty-nine (88%) patients had an adverse event grade ≥ 3 including two fatal adverse events that were judged not to be treatment-related. CONCLUSION: The addition of perioperative durvalumab to neoadjuvant chemotherapy in patients with stage IIIA(N2) non-small-cell lung cancer is safe and exceeds historical data of chemotherapy alone with a high MPR and an encouraging 1-year EFS rate of 73%.
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