In one of 4 publications in the NEJM describing the results of clinical trials evaluating immune checkpoint blockade (ICB), released in concert with the 2018 AACR Annual Meeting, Hellman et al. demonstrated that high tumor mutational burden (> 10 mutations per megabase as determined by the FoundationOne CDx assay) was effective in predicting improved progression-free survival for first line non-small cell lung cancer patients treated with a combination of nivolumab and ipilimumab versus platinum doublet chemotherapy. Please click here for our summary of the other ICB clinical trial results (Eggermont, Gandhi, and Pardoll).
Background Nivolumab plus ipilimumab showed promising efficacy for the treatment of non-small-cell lung cancer (NSCLC) in a phase 1 trial, and tumor mutational burden has emerged as a potential biomarker of benefit. In this part of an open-label, multipart, phase 3 trial, we examined progression-free survival with nivolumab plus ipilimumab versus chemotherapy among patients with a high tumor mutational burden (>/=10 mutations per megabase). Methods We enrolled patients with stage IV or recurrent NSCLC that was not previously treated with chemotherapy. Those with a level of tumor programmed death ligand 1 (PD-L1) expression of at least 1% were randomly assigned, in a 1:1:1 ratio, to receive nivolumab plus ipilimumab, nivolumab monotherapy, or chemotherapy; those with a tumor PD-L1 expression level of less than 1% were randomly assigned, in a 1:1:1 ratio, to receive nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy. Tumor mutational burden was determined by the FoundationOne CDx assay. Results Progression-free survival among patients with a high tumor mutational burden was significantly longer with nivolumab plus ipilimumab than with chemotherapy. The 1-year progression-free survival rate was 42.6% with nivolumab plus ipilimumab versus 13.2% with chemotherapy, and the median progression-free survival was 7.2 months (95% confidence interval [CI], 5.5 to 13.2) versus 5.5 months (95% CI, 4.4 to 5.8) (hazard ratio for disease progression or death, 0.58; 97.5% CI, 0.41 to 0.81; P<0.001). The objective response rate was 45.3% with nivolumab plus ipilimumab and 26.9% with chemotherapy. The benefit of nivolumab plus ipilimumab over chemotherapy was broadly consistent within subgroups, including patients with a PD-L1 expression level of at least 1% and those with a level of less than 1%. The rate of grade 3 or 4 treatment-related adverse events was 31.2% with nivolumab plus ipilimumab and 36.1% with chemotherapy. Conclusions Progression-free survival was significantly longer with first-line nivolumab plus ipilimumab than with chemotherapy among patients with NSCLC and a high tumor mutational burden, irrespective of PD-L1 expression level. The results validate the benefit of nivolumab plus ipilimumab in NSCLC and the role of tumor mutational burden as a biomarker for patient selection. (Funded by Bristol-Myers Squibb and Ono Pharmaceutical; CheckMate 227 ClinicalTrials.gov number, NCT02477826 .).
Author Info: (1) From Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu
Author Info: (1) From Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hopital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundacion Arturo Lopez Perez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncologicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.). (2) From Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hopital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundacion Arturo Lopez Perez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncologicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.). (3) From Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hopital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundacion Arturo Lopez Perez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncologicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.). (4) From Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hopital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundacion Arturo Lopez Perez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncologicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.). (5) From Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hopital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundacion Arturo Lopez Perez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncologicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.). (6) From Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hopital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundacion Arturo Lopez Perez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncologicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.). (7) From Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hopital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundacion Arturo Lopez Perez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncologicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.). (8) From Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hopital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundacion Arturo Lopez Perez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncologicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.). (9) From Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hopital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundacion Arturo Lopez Perez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncologicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.). (10) From Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hopital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundacion Arturo Lopez Perez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncologicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.). (11) From Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hopital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundacion Arturo Lopez Perez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncologicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.). (12) From Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hopital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundacion Arturo Lopez Perez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncologicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.). (13) From Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hopital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundacion Arturo Lopez Perez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncologicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.). (14) From Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hopital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundacion Arturo Lopez Perez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncologicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.). (15) From Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hopital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundacion Arturo Lopez Perez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncologicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.). (16) From Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hopital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundacion Arturo Lopez Perez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncologicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.). (17) From Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hopital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundacion Arturo Lopez Perez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncologicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.). (18) From Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hopital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundacion Arturo Lopez Perez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncologicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.). (19) From Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hopital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundacion Arturo Lopez Perez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncologicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.). (20) From Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hopital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundacion Arturo Lopez Perez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncologicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.). (21) From Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hopital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundacion Arturo Lopez Perez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncologicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.). (22) From Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hopital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundacion Arturo Lopez Perez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncologicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.). (23) From Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hopital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundacion Arturo Lopez Perez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncologicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.). (24) From Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hopital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundacion Arturo Lopez Perez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncologicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.).
