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

被引：236

作者：

Rothschild, Sacha, I ^{[1
,2
]}

Zippelius, Alfred ^{[1
,2
]}

Eboulet, Eric, I ^{[3
]}

Prince, Spasenija Savic ^{[4
]}

Betticher, Daniel ^{[5
]}

Bettini, Adrienne ^{[5
]}

Frueh, Martin ^{[6
,7
]}

Joerger, Markus ^{[6
]}

Lardinois, Didier ^{[8
]}

Gelpke, Hans ^{[9
]}

Mauti, Laetitia A. ^{[10
]}

Britschgi, Christian ^{[11
]}

Weder, Walter ^{[12
]}

Peters, Solange ^{[13
]}

Mark, Michael ^{[14
]}

Cathomas, Richard ^{[14
]}

Ochsenbein, Adrian F. ^{[7
]}

Janthur, Wolf-Dieter ^{[15
]}

Waibel, Christine ^{[16
]}

Mach, Nicolas ^{[17
]}

Froesch, Patrizia ^{[18
]}

Buess, Martin ^{[19
]}

Bohanes, Pierre ^{[20
]}

Godar, Gilles ^{[3
]}

Rusterholz, Corinne ^{[3
]}

Gonzalez, Michel ^{[21
]}

Pless, Miklos ^{[10
]}

机构：

[1] Univ Hosp Basel, Dept Med Oncol, Petersgraben 4, CH-4031 Basel, Switzerland

[2] Univ Hosp Basel, Comprehens Canc Ctr, Petersgraben 4, CH-4031 Basel, Switzerland

[3] SAKK Coordinating Ctr, Bern, Switzerland

[4] Univ Hosp Basel, Inst Med Genet & Pathol, Pathol, Basel, Switzerland

[5] HFR Fribourg Hop Fribourgeois, Dept Oncol, Fribourg, Switzerland

[6] Cantonal Hosp St Gallen, Dept Oncol Hematol, St Gallen, Switzerland

[7] Inselspital Bern, Dept Oncol, Bern, Switzerland

[8] Univ Hosp Basel, Div Thorac Surg, Basel, Switzerland

[9] Cantonal Hosp Winterthur, Dept Thorac & Visceral Surg, Winterthur, Switzerland

[10] Cantonal Hosp Winterthur, Dept Oncol, Winterthur, Switzerland

[11] Univ Zurich, Univ Hosp Zurich, Comprehens Canc Ctr Zurich, Dept Med Oncol & Hematol, Zurich, Switzerland

[12] Univ Hosp Zurich, Dept Thorac Surg, Zurich, Switzerland

[13] Univ Hosp Lausanne CHUV, Dept Oncol, Lausanne, Switzerland

[14] Cantonal Hosp Graubunden, Divison Oncol Hematol, Chur, Switzerland

[15] Cantonal Hosp Aarau, Dept Oncol Hematol, Aarau, Switzerland

[16] Cantonal Hosp Baden, Dept Oncol, Baden, Switzerland

[17] Univ Hosp Geneva, Dept Oncol, Geneva, Switzerland

[18] Oncol Inst Southern Switzerland, Bellinzona, Switzerland

[19] St Clara Hosp, Div Med Oncol, Basel, Switzerland

[20] Ctr Chimiotherapie Anticancereuse, Lausanne, Switzerland

[21] Univ Hosp Lausanne CHUV, Dept Thorac Surg, Lausanne, Switzerland

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2021年 / 39卷 / 26期

关键词：

OPEN-LABEL; RESECTION; SURGERY; CHEMORADIOTHERAPY; CLASSIFICATION; GUIDELINES;

D O I：

10.1200/JCO.21.00276

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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/m(2) and docetaxel 85 mg/m(2) 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%. (C) 2021 by American Society of Clinical Oncology

引用

页码：2872 / +

页数：12

共 30 条

[1] Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial [J].

Albain, Kathy S. ;

Swann, R. Suzanne ;

Rusch, Valerie W. ;

Turrisi, Andrew T., III ;

Shepherd, Frances A. ;

Smith, Colum ;

Chen, Yuhchyau ;

Livingston, Robert B. ;

Feins, Richard H. ;

Gandara, David R. ;

Fry, Willard A. ;

Darling, Gail ;

Johnson, David H. ;

Green, Mark R. ;

Miller, Robert C. ;

Ley, Joanne ;

Sause, Willliam T. ;

Cox, James D. .

LANCET, 2009, 374 (9687) :379-386

[2] Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC [J].

Antonia, S. J. ;

Villegas, A. ;

Daniel, D. ;

Vicente, D. ;

Murakami, S. ;

Hui, R. ;

Kurata, T. ;

Chiappori, A. ;

Lee, K. H. ;

de Wit, M. ;

Cho, B. C. ;

Bourhaba, M. ;

Quantin, X. ;

Tokito, T. ;

Mekhail, T. ;

Planchard, D. ;

Kim, Y. -C. ;

Karapetis, C. S. ;

Hiret, S. ;

Ostoros, G. ;

Kubota, K. ;

Gray, J. E. ;

Paz-Ares, L. ;

Carpeno, J. de Castro ;

Faivre-Finn, C. ;

Reck, M. ;

Vansteenkiste, J. ;

Spigel, D. R. ;

Wadsworth, C. ;

Melillo, G. ;

Taboada, M. ;

Dennis, P. A. ;

Ozguroglu, M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2018, 379 (24) :2342-2350

[3] Prognostic factors affecting long-term outcomes in patients with resected stage IIIA pN2 non-small-cell lung cancer:: 5-year follow-up of a phase II study [J].

Betticher, DC ;

Schmitz, SFH ;

Tötsch, M ;

Hansen, E ;

Joss, C ;

von Briel, C ;

Schmid, R ;

Pless, M ;

Habicht, J ;

Roth, AD ;

Spiliopoulos, A ;

Stahel, R ;

Weder, W ;

Stupp, R ;

Egli, F ;

Furrer, M ;

Honegger, H ;

Wernli, M ;

Cerny, T ;

Ris, HB .

BRITISH JOURNAL OF CANCER, 2006, 94 (08) :1099-1106

[4] Mediastinal lymph node clearance after docetaxel-cisplatin Neoadjuvant chemotherapy is prognostic of survival in patients with stage IIIA pN2 non-small-cell lung cancer:: A multicenter phase II trial [J].

Betticher, DC ;

Schmitz, SFH ;

Tötsch, M ;

Hansen, E ;

Joss, C ;

von Briel, C ;

Schmid, RA ;

Pless, M ;

Habicht, J ;

Roth, AD ;

Spiliopoulos, A ;

Stahel, R ;

Weder, W ;

Stupp, R ;

Egli, F ;

Furrer, M ;

Honegger, H ;

Wernli, M ;

Cerny, T ;

Ris, HB .

JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (09) :1752-1759

[5] The European Respiratory Society and European Society of Thoracic Surgeons clinical guidelines for evaluating fitness for radical treatment (surgery and chemoradiotherapy) in patients with lung cancer [J].

Brunelli, Alessandro ;

Charloux, Anne ;

Bolliger, Chris T. ;

Rocco, Gaetano ;

Sculier, Jean-Paul ;

Varela, Gonzalo ;

Licker, Marc ;

Ferguson, Mark K. ;

Faivre-Finn, Corinne ;

Huber, Rudolf Maria ;

Clini, Enrico M. ;

Win, Thida ;

De Ruysscher, Dirk ;

Goldman, Lee .

EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY, 2009, 36 (01) :181-184

[6] Neoadjuvant nivolumab or nivolumab plus ipilimumab in operable non-small cell lung cancer: the phase 2 randomized NEOSTAR trial [J].

Cascone, Tina ;

William, William N., Jr. ;

Weissferdt, Annikka ;

Leung, Cheuk H. ;

Lin, Heather Y. ;

Pataer, Apar ;

Godoy, Myrna C. B. ;

Carter, Brett W. ;

Federico, Lorenzo ;

Reuben, Alexandre ;

Khan, Md Abdul Wadud ;

Dejima, Hitoshi ;

Francisco-Cruz, Alejandro ;

Parra, Edwin R. ;

Solis, Luisa M. ;

Fujimoto, Junya ;

Tran, Hai T. ;

Kalhor, Neda ;

Fossella, Frank V. ;

Mott, Frank E. ;

Tsao, Anne S. ;

Blumenschein, George, Jr. ;

Le, Xiuning ;

Zhang, Jianjun ;

Skoulidis, Ferdinandos ;

Kurie, Jonathan M. ;

Altan, Mehmet ;

Lu, Charles ;

Glisson, Bonnie S. ;

Byers, Lauren Averett ;

Elamin, Yasir Y. ;

Mehran, Reza J. ;

Rice, David C. ;

Walsh, Garrett L. ;

Hofstetter, Wayne L. ;

Roth, Jack A. ;

Antonoff, Mara B. ;

Kadara, Humam ;

Haymaker, Cara ;

Bernatchez, Chantale ;

Ajami, Nadim J. ;

Jenq, Robert R. ;

Sharma, Padmanee ;

Allison, James P. ;

Futreal, Andrew ;

Wargo, Jennifer A. ;

Wistuba, Ignacio I. ;

Swisher, Stephen G. ;

Lee, J. Jack ;

Gibbons, Don L. .

NATURE MEDICINE, 2021, 27 (03) :504-+

[7]

Cascone T, 2019, J CLIN ONCOL, V37

[8] Phase III Study of Surgery Versus Definitive Concurrent Chemoradiotherapy Boost in Patients With Resectable Stage IIIA(N2) and Selected IIIB Non-Small-Cell Lung Cancer After Induction Chemotherapy and Concurrent Chemoradiotherapy (ESPATUE) [J].

Eberhardt, Wilfried Ernst Erich ;

Poettgen, Christoph ;

Gauler, Thomas Christoph ;

Friedel, Godehard ;

Veit, Stefanie ;

Heinrich, Vanessa ;

Welter, Stefan ;

Budach, Wilfried ;

Spengler, Werner ;

Kimmich, Martin ;

Fischer, Berthold ;

Schmidberger, Heinz ;

De Ruysscher, Dirk ;

Belka, Claus ;

Cordes, Sebastian ;

Hepp, Rodrigo ;

Luetke-Brintrup, Diana ;

Lehmann, Nils ;

Schuler, Martin ;

Joeckel, Karl-Heinz ;

Stamatis, Georgios ;

Stuschke, Martin .

JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (35) :4194-+

[9] Neoadjuvant PD-1 Blockade in Resectable Lung Cancer [J].

Forde, P. M. ;

Chaft, J. E. ;

Smith, K. N. ;

Anagnostou, V. ;

Cottrell, T. R. ;

Hellmann, M. D. ;

Zahurak, M. ;

Yang, S. C. ;

Jones, D. R. ;

Broderick, S. ;

Battafarano, R. J. ;

Velez, M. J. ;

Rekhtman, N. ;

Olah, Z. ;

Naidoo, J. ;

Marrone, K. A. ;

Verde, F. ;

Guo, H. ;

Zhang, J. ;

Caushi, J. X. ;

Chan, H. Y. ;

Sidhom, J. -W. ;

Scharpf, R. B. ;

White, J. ;

Gabrielson, E. ;

Wang, H. ;

Rosner, G. L. ;

Rusch, V. ;

Wolchok, J. D. ;

Merghoub, T. ;

Taube, J. M. ;

Velculescu, V. E. ;

Topalian, S. L. ;

Brahmer, J. R. ;

Pardoll, D. M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2018, 378 (21) :1976-1986

[10] Multimodal Treatment in Operable Stage III NSCLC: A Pooled Analysis on Long-Term Results of Three SAKK trials (SAKK 16/96, 16/00, and 16/01) [J].

Fruh, Martin ;

Betticher, Daniel C. ;

Stupp, Roger ;

Xyrafas, Alexandros ;

Peters, Solange ;

Ris, Hans Beat ;

Mirimanoff, Rene Olivier ;

Ochsenbein, Adrian F. ;

Schmid, Ralph ;

Matzinger, Oscar ;

Stahel, Rolf A. ;

Weder, Walter ;

Guckenberger, Matthias ;

Rothschild, Sacha I. ;

Lardinois, Didier ;

Mach, Nicholas ;

Mark, Michael ;

Gautschi, Oliver ;

Thierstein, Sandra ;

Rudolf, Christine Biaggi ;

Pless, Miklos .

JOURNAL OF THORACIC ONCOLOGY, 2019, 14 (01) :115-123

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