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N Engl J Med. 2018 Jun 14;378(24):2288-2301. doi: 10.1056/NEJMoa1716948. Epub 2018 Jun 4.

Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC.

Collaborators (307)

Ahualli A, Jarchum G, Kaen DL, Kahl S, Kotliar M, Kowalyszyn RD, Lerzo G, Magri I, Martin C, Pastor A, Picon P, Streich G, Varela M, Blinman P, Boyer M, Crombie C, Gauden S, Gill S, Hughes B, John T, Joshi A, Kosmider S, Lewis C, Millward M, Nordman I, Nott L, O'Byrne K, Parnis F, Potasz N, Richardson G, Singhal N, Eckmayr J, Greil R, Goeminne JC, Paulus A, Aragao B, Bruno LA, Campos C, Costamilan RdC, Dettino A, Faccio A, Girotto G, Matias D, Murad AM, Schwartsmann G, Silva C, Tadokoro H, Dimitrov B, Ilieva R, Kalev D, Kanarev V, Koleva M, Koynov K, Mihaylova Z, Cohen V, Cournoyer G, Rorke S, Rothenstein J, Spadafora S, Aren O, Orellana Ulunque E, Yanez E, Audigier Valette C, Bennouna J, Berard H, Coudert B, Dayen C, Denis F, Fabre Guillevin E, Foa C, Gazaille V, Le Moulec S, Mazieres J, Morere JF, Veillon R, Bargon J, Behringer D, Dickgreber NJ, Engel-Riedel W, Fischer JR, Hackanson B, Kokowski K, Kollmeier J, Loges S, Schulz C, Schütte W, Serke M, Stauder H, Steppert C, Wehler T, Weissinger F, Wermke M, Wesseler C, Allegrini G, Amoroso D, Barone C, Borra G, Carteni G, Defraia E, Falcone A, Grossi F, Mencoboni M, Migliorino MR, Pazzola A, Soto Parra H, Tonini G, Azuma K, Fukuhara T, Ichiki M, Ikeda S, Kawaguchi T, Kim YH, Kishi K, Otani S, Seto T, Takeda Y, Tanaka H, Yamamoto N, Yokota S, Yokoyama T, Purkalne G, Zvirbule Z, Cicenas S, Filipauskiene J, Dominguez A, Gomez A, Lazaro Leon JM, Lopez Y, Aerts JGJV, Barlo N, Biesma B, Dingemans AM, Hashemi S, Keizer-van't Westeinde S, Lammers E, Mansour K, Schramel F, Snijders D, van Haarst JM, van Lindert A, Wilschut F, Aleman D, Cisneros Tipismana R, Kobashigawa A, Mas L, Morón Escobar HD, Almodovar T, Araujo A, Azevedo I, Barata F, Queiroga H, Saturnino Duarte de Brito U, Teixeira E, Biakhov M, Galiulin R, Gorbunova V, Karaseva N, Kovalenko N, Penkov K, Poltoratskiy A, Vasiliev A, Zhiltsova E, Leong SS, Lim D, Beniak J, Chovanec J, Godal R, Kasan P, Porubska M, Alvarez R, Areses Manrique MdC, Barneto Aranda IC, De Castro Carpeno J, Domine Gomez M, Felip Font E, Garcia Garcia Y, Garrido Lopez P, Girones Sarrio R, Gonzalez Larriba JL, Insa Molla A, Jimenez Munarriz B, Lopez-Brea Piqueras M, Nadal E, Ponce Aix S, Taus Garcia A, Terrasa Pons J, Vazquez Estevez S, Viñolas Segarra N, Vikström A, Frueh M, Gautschi O, Lohri A, Ochsenbein A, Chang GC, Chen CH, Chen WT, Chen YM, Ho CL, Hsia TC, Hsieh RK, Huang MS, Li CT, Lin YC, Liu CY, Su WC, Yu CJ, Adamchuk H, Andrusenko O, Bondarenko I, Chornobai A, Hotko Y, Ivashchuk O, Kolesnik O, Kryzhanivska A, Odarchenko S, Ogorodnikova N, Rusyn A, Shamrai V, Shapovalov D, Vasylyev L, Vynnychenko I, Abdel Karim N, Almubarak M, Al-Nsour M, Assikis V, Baker S, Batus M, Beatty P, Becker K, Belman N, Bernicker E, Braiteh F, Bui L, Carr L, Chaudhry A, Cheng H, Chitneni S, Cohenuram M, Daniels G, Dean-Colomb W, DeVore R III, DiStefano A, Dobrescu A, Drew DZ, Eisenberg P, Erickson B, Eskander E, Fabregas J, Faller B, Fiorillo J, Goldschmidt J Jr, Goueli B, Gurubhagavatula S, Halibey B, Hamm J, Herman J, Hoffman P, Hooberman A, Jhangiani H, Kabbinavar F, Karnad A, Keogh GP, Kirshner E, Koh H, Kono S, Kosty M, Kotiah S, Kozloff M, Kuzma C, Lakhani N, Lukas J, Martin W, Masood N, Matthews-Smith V, McCann J, Menefee M, Mitchell BR, Naidu S, Narang M, Natale R, Niederman T, Nissenblatt M, Ou SH, Paschold JC, Raez LE, Rafiyath S, Rodriguez E, Rosales J, Rothman J, Sabbath K, Sanz-Altamira P, Schnell FM, Shtivelband M, Silberberg J, Socoteanu M, Spira AI, Stella P, Subramanian J, Swanson PM, Telivala B, Tsai F, Tummala M, VanderWalde A, Velcheti V, West H, Yanagihara R, Zylla D.

Author information

1
From the Florida Hospital Cancer Institute, Orlando (M.A.S.); Rocky Mountain Cancer Centers, Denver (R.M.J.); US Oncology, Houston (R.M.J.); Azienda Unità Sanitaria Locale della Romagna, Ravenna, Italy (F.C.); Instituto Nacional del Torax, Santiago, Chile (F.O.); Moscow City Oncology Hospital, Moscow (D.S.); National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan (N.N.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain (D.R.-A.); Centre Hospitalier Universitaire de Grenoble Alpes, Grenoble (D.M.-S.), and Aix Marseille University, Assistance Publique-Hôpitaux de Marseille, Marseille (F.B.) - both in France; New England Cancer Specialists, Scarborough, ME (C.A.T.); Allegheny Health Network Cancer Institute, Pittsburgh (G.F.); Genentech, South San Francisco, CA (C.K., A.L., S.C., Y.D., Y.S., M.K., A.L.-C., A.S.); and Lung Clinic Grosshansdorf, Airway Research Center North, German Center of Lung Research, Grosshansdorf, Germany (M.R.).

Abstract

BACKGROUND:

The cancer-cell-killing property of atezolizumab may be enhanced by the blockade of vascular endothelial growth factor-mediated immunosuppression with bevacizumab. This open-label, phase 3 study evaluated atezolizumab plus bevacizumab plus chemotherapy in patients with metastatic nonsquamous non-small-cell lung cancer (NSCLC) who had not previously received chemotherapy.

METHODS:

We randomly assigned patients to receive atezolizumab plus carboplatin plus paclitaxel (ACP), bevacizumab plus carboplatin plus paclitaxel (BCP), or atezolizumab plus BCP (ABCP) every 3 weeks for four or six cycles, followed by maintenance therapy with atezolizumab, bevacizumab, or both. The two primary end points were investigator-assessed progression-free survival both among patients in the intention-to-treat population who had a wild-type genotype (WT population; patients with EGFR or ALK genetic alterations were excluded) and among patients in the WT population who had high expression of an effector T-cell (Teff) gene signature in the tumor (Teff-high WT population) and overall survival in the WT population. The ABCP group was compared with the BCP group before the ACP group was compared with the BCP group.

RESULTS:

In the WT population, 356 patients were assigned to the ABCP group, and 336 to the BCP group. The median progression-free survival was longer in the ABCP group than in the BCP group (8.3 months vs. 6.8 months; hazard ratio for disease progression or death, 0.62; 95% confidence interval [CI], 0.52 to 0.74; P<0.001); the corresponding values in the Teff-high WT population were 11.3 months and 6.8 months (hazard ratio, 0.51 [95% CI, 0.38 to 0.68]; P<0.001). Progression-free survival was also longer in the ABCP group than in the BCP group in the entire intention-to-treat population (including those with EGFR or ALK genetic alterations) and among patients with low or negative programmed death ligand 1 (PD-L1) expression, those with low Teff gene-signature expression, and those with liver metastases. Median overall survival among the patients in the WT population was longer in the ABCP group than in the BCP group (19.2 months vs. 14.7 months; hazard ratio for death, 0.78; 95% CI, 0.64 to 0.96; P=0.02). The safety profile of ABCP was consistent with previously reported safety risks of the individual medicines.

CONCLUSIONS:

The addition of atezolizumab to bevacizumab plus chemotherapy significantly improved progression-free survival and overall survival among patients with metastatic nonsquamous NSCLC, regardless of PD-L1 expression and EGFR or ALK genetic alteration status. (Funded by F. Hoffmann-La Roche/Genentech; IMpower150 ClinicalTrials.gov number, NCT02366143 .).

PMID:
29863955
DOI:
10.1056/NEJMoa1716948
[Indexed for MEDLINE]
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