Phase 3 Trial of Cabozantinib to Treat Advanced Neuroendocrine Tumors.

Journal

The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562

Informations de publication

Date de publication:
16 Sep 2024
Historique:
medline: 17 9 2024
pubmed: 17 9 2024
entrez: 16 9 2024
Statut: aheadofprint

Résumé

Treatment options for patients with advanced neuroendocrine tumors are limited. The efficacy of cabozantinib in the treatment of previously treated, progressive extrapancreatic or pancreatic neuroendocrine tumors is unclear. We enrolled two independent cohorts of patients - those with extrapancreatic neuroendocrine tumors and those with pancreatic neuroendocrine tumors - who had received peptide receptor radionuclide therapy or targeted therapy or both. Patients were randomly assigned in a 2:1 ratio to receive cabozantinib at a dose of 60 mg daily or placebo. The primary end point was progression-free survival as assessed by blinded independent central review. Key secondary end points included objective response, overall survival, and safety. In the cohort of 203 patients with extrapancreatic neuroendocrine tumors, the median progression-free survival with cabozantinib was 8.4 months, as compared with 3.9 months with placebo (stratified hazard ratio for progression or death, 0.38; 95% confidence interval [CI], 0.25 to 0.59; P<0.001). In the cohort of 95 patients with pancreatic neuroendocrine tumors, the median progression-free survival with cabozantinib was 13.8 months, as compared with 4.4 months with placebo (stratified hazard ratio, 0.23; 95% CI, 0.12 to 0.42; P<0.001). The incidence of confirmed objective response with cabozantinib was 5% and 19% among patients with extrapancreatic and pancreatic neuroendocrine tumors, respectively, as compared with 0% with placebo. Grade 3 or higher adverse events were noted in 62 to 65% of the patients treated with cabozantinib, as compared with 23 to 27% of the patients who received placebo. Common treatment-related adverse events of grade 3 or higher included hypertension, fatigue, diarrhea, and thromboembolic events. Cabozantinib, as compared with placebo, significantly improved progression-free survival in patients with previously treated, progressive advanced extrapancreatic or pancreatic neuroendocrine tumors. Adverse events were consistent with the known safety profile of cabozantinib. (Funded by the National Cancer Institute and others; CABINET ClinicalTrials.gov number, NCT03375320.).

Sections du résumé

BACKGROUND BACKGROUND
Treatment options for patients with advanced neuroendocrine tumors are limited. The efficacy of cabozantinib in the treatment of previously treated, progressive extrapancreatic or pancreatic neuroendocrine tumors is unclear.
METHODS METHODS
We enrolled two independent cohorts of patients - those with extrapancreatic neuroendocrine tumors and those with pancreatic neuroendocrine tumors - who had received peptide receptor radionuclide therapy or targeted therapy or both. Patients were randomly assigned in a 2:1 ratio to receive cabozantinib at a dose of 60 mg daily or placebo. The primary end point was progression-free survival as assessed by blinded independent central review. Key secondary end points included objective response, overall survival, and safety.
RESULTS RESULTS
In the cohort of 203 patients with extrapancreatic neuroendocrine tumors, the median progression-free survival with cabozantinib was 8.4 months, as compared with 3.9 months with placebo (stratified hazard ratio for progression or death, 0.38; 95% confidence interval [CI], 0.25 to 0.59; P<0.001). In the cohort of 95 patients with pancreatic neuroendocrine tumors, the median progression-free survival with cabozantinib was 13.8 months, as compared with 4.4 months with placebo (stratified hazard ratio, 0.23; 95% CI, 0.12 to 0.42; P<0.001). The incidence of confirmed objective response with cabozantinib was 5% and 19% among patients with extrapancreatic and pancreatic neuroendocrine tumors, respectively, as compared with 0% with placebo. Grade 3 or higher adverse events were noted in 62 to 65% of the patients treated with cabozantinib, as compared with 23 to 27% of the patients who received placebo. Common treatment-related adverse events of grade 3 or higher included hypertension, fatigue, diarrhea, and thromboembolic events.
CONCLUSIONS CONCLUSIONS
Cabozantinib, as compared with placebo, significantly improved progression-free survival in patients with previously treated, progressive advanced extrapancreatic or pancreatic neuroendocrine tumors. Adverse events were consistent with the known safety profile of cabozantinib. (Funded by the National Cancer Institute and others; CABINET ClinicalTrials.gov number, NCT03375320.).

Identifiants

DOI: 10.1056/NEJMoa2403991 PMID: 39282913
pubmed: 39282913
doi: 10.1056/NEJMoa2403991
doi:

Banques de données

ClinicalTrials.gov
['NCT03375320']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NCI NIH HHS
ID : U10CA180820
Pays : United States
Organisme : NCI NIH HHS
ID : U10CA180821 and U10CA180882
Pays : United States
Organisme : NCI NIH HHS
ID : U10CA180868
Pays : United States
Organisme : NCI NIH HHS
ID : U10CA180888
Pays : United States
Organisme : NCI NIH HHS
ID : UG1CA189856, UG1CA232760, UG1CA233180, UG1CA233290
Pays : United States
Organisme : NCI NIH HHS
ID : UG1CA233329, UG1CA233331
Pays : United States

Informations de copyright

Copyright © 2024 Massachusetts Medical Society.

Auteurs

Jennifer A Chan (JA)

From Dana-Farber Cancer Institute (J.A.C., J.A.M.), Boston Medical Center (M.H.K.), and Boston University (M.H.K.) - all in Boston; the Alliance Statistics and Data Management Center, Mayo Clinic (S.G., T.Z., S.P., F.-S.O.), and Mayo Clinic Comprehensive Cancer Center (T.R.H.) - both in Rochester, MN; Wright Center of Innovation and the Imaging and Radiation Oncology Core, University of Cincinnati, Cincinnati (M.V.K.), and the Ohio State University Comprehensive Cancer Center, Columbus (B.K.) - both in Ohio; the University of California, San Francisco, San Francisco (S.B.), and Stanford Cancer Center, Stanford (S.S.) - both in California; Alliance Statistics and Data Management Center, Mayo Clinic, Scottsdale, AZ (A.C.D.); the University of Hawaii Cancer Center, Honolulu (J.A.); the Alliance Protocol Operations Office, University of Chicago, Chicago (A.S.); Mount Sinai Medical Center (E.M.W.) and Memorial Sloan Kettering Cancer Center (N.R., E.M.O.) - both in New York; Washington University School of Medicine and Siteman Cancer Center, St. Louis (N.A.T.); the University of New Mexico Comprehensive Cancer Center, Albuquerque (B.T.); Fox Chase Cancer Center, Philadelphia (N.V.); M.D. Anderson Cancer Center, Houston (A.D.); Moffitt Cancer Center, Tampa, FL (J.R.S.); and the National Cancer Institute, Bethesda, MD (E.C.K.).

Susan Geyer (S)

From Dana-Farber Cancer Institute (J.A.C., J.A.M.), Boston Medical Center (M.H.K.), and Boston University (M.H.K.) - all in Boston; the Alliance Statistics and Data Management Center, Mayo Clinic (S.G., T.Z., S.P., F.-S.O.), and Mayo Clinic Comprehensive Cancer Center (T.R.H.) - both in Rochester, MN; Wright Center of Innovation and the Imaging and Radiation Oncology Core, University of Cincinnati, Cincinnati (M.V.K.), and the Ohio State University Comprehensive Cancer Center, Columbus (B.K.) - both in Ohio; the University of California, San Francisco, San Francisco (S.B.), and Stanford Cancer Center, Stanford (S.S.) - both in California; Alliance Statistics and Data Management Center, Mayo Clinic, Scottsdale, AZ (A.C.D.); the University of Hawaii Cancer Center, Honolulu (J.A.); the Alliance Protocol Operations Office, University of Chicago, Chicago (A.S.); Mount Sinai Medical Center (E.M.W.) and Memorial Sloan Kettering Cancer Center (N.R., E.M.O.) - both in New York; Washington University School of Medicine and Siteman Cancer Center, St. Louis (N.A.T.); the University of New Mexico Comprehensive Cancer Center, Albuquerque (B.T.); Fox Chase Cancer Center, Philadelphia (N.V.); M.D. Anderson Cancer Center, Houston (A.D.); Moffitt Cancer Center, Tampa, FL (J.R.S.); and the National Cancer Institute, Bethesda, MD (E.C.K.).

Tyler Zemla (T)

From Dana-Farber Cancer Institute (J.A.C., J.A.M.), Boston Medical Center (M.H.K.), and Boston University (M.H.K.) - all in Boston; the Alliance Statistics and Data Management Center, Mayo Clinic (S.G., T.Z., S.P., F.-S.O.), and Mayo Clinic Comprehensive Cancer Center (T.R.H.) - both in Rochester, MN; Wright Center of Innovation and the Imaging and Radiation Oncology Core, University of Cincinnati, Cincinnati (M.V.K.), and the Ohio State University Comprehensive Cancer Center, Columbus (B.K.) - both in Ohio; the University of California, San Francisco, San Francisco (S.B.), and Stanford Cancer Center, Stanford (S.S.) - both in California; Alliance Statistics and Data Management Center, Mayo Clinic, Scottsdale, AZ (A.C.D.); the University of Hawaii Cancer Center, Honolulu (J.A.); the Alliance Protocol Operations Office, University of Chicago, Chicago (A.S.); Mount Sinai Medical Center (E.M.W.) and Memorial Sloan Kettering Cancer Center (N.R., E.M.O.) - both in New York; Washington University School of Medicine and Siteman Cancer Center, St. Louis (N.A.T.); the University of New Mexico Comprehensive Cancer Center, Albuquerque (B.T.); Fox Chase Cancer Center, Philadelphia (N.V.); M.D. Anderson Cancer Center, Houston (A.D.); Moffitt Cancer Center, Tampa, FL (J.R.S.); and the National Cancer Institute, Bethesda, MD (E.C.K.).

Michael V Knopp (MV)

From Dana-Farber Cancer Institute (J.A.C., J.A.M.), Boston Medical Center (M.H.K.), and Boston University (M.H.K.) - all in Boston; the Alliance Statistics and Data Management Center, Mayo Clinic (S.G., T.Z., S.P., F.-S.O.), and Mayo Clinic Comprehensive Cancer Center (T.R.H.) - both in Rochester, MN; Wright Center of Innovation and the Imaging and Radiation Oncology Core, University of Cincinnati, Cincinnati (M.V.K.), and the Ohio State University Comprehensive Cancer Center, Columbus (B.K.) - both in Ohio; the University of California, San Francisco, San Francisco (S.B.), and Stanford Cancer Center, Stanford (S.S.) - both in California; Alliance Statistics and Data Management Center, Mayo Clinic, Scottsdale, AZ (A.C.D.); the University of Hawaii Cancer Center, Honolulu (J.A.); the Alliance Protocol Operations Office, University of Chicago, Chicago (A.S.); Mount Sinai Medical Center (E.M.W.) and Memorial Sloan Kettering Cancer Center (N.R., E.M.O.) - both in New York; Washington University School of Medicine and Siteman Cancer Center, St. Louis (N.A.T.); the University of New Mexico Comprehensive Cancer Center, Albuquerque (B.T.); Fox Chase Cancer Center, Philadelphia (N.V.); M.D. Anderson Cancer Center, Houston (A.D.); Moffitt Cancer Center, Tampa, FL (J.R.S.); and the National Cancer Institute, Bethesda, MD (E.C.K.).

Spencer Behr (S)

From Dana-Farber Cancer Institute (J.A.C., J.A.M.), Boston Medical Center (M.H.K.), and Boston University (M.H.K.) - all in Boston; the Alliance Statistics and Data Management Center, Mayo Clinic (S.G., T.Z., S.P., F.-S.O.), and Mayo Clinic Comprehensive Cancer Center (T.R.H.) - both in Rochester, MN; Wright Center of Innovation and the Imaging and Radiation Oncology Core, University of Cincinnati, Cincinnati (M.V.K.), and the Ohio State University Comprehensive Cancer Center, Columbus (B.K.) - both in Ohio; the University of California, San Francisco, San Francisco (S.B.), and Stanford Cancer Center, Stanford (S.S.) - both in California; Alliance Statistics and Data Management Center, Mayo Clinic, Scottsdale, AZ (A.C.D.); the University of Hawaii Cancer Center, Honolulu (J.A.); the Alliance Protocol Operations Office, University of Chicago, Chicago (A.S.); Mount Sinai Medical Center (E.M.W.) and Memorial Sloan Kettering Cancer Center (N.R., E.M.O.) - both in New York; Washington University School of Medicine and Siteman Cancer Center, St. Louis (N.A.T.); the University of New Mexico Comprehensive Cancer Center, Albuquerque (B.T.); Fox Chase Cancer Center, Philadelphia (N.V.); M.D. Anderson Cancer Center, Houston (A.D.); Moffitt Cancer Center, Tampa, FL (J.R.S.); and the National Cancer Institute, Bethesda, MD (E.C.K.).

Sydney Pulsipher (S)

From Dana-Farber Cancer Institute (J.A.C., J.A.M.), Boston Medical Center (M.H.K.), and Boston University (M.H.K.) - all in Boston; the Alliance Statistics and Data Management Center, Mayo Clinic (S.G., T.Z., S.P., F.-S.O.), and Mayo Clinic Comprehensive Cancer Center (T.R.H.) - both in Rochester, MN; Wright Center of Innovation and the Imaging and Radiation Oncology Core, University of Cincinnati, Cincinnati (M.V.K.), and the Ohio State University Comprehensive Cancer Center, Columbus (B.K.) - both in Ohio; the University of California, San Francisco, San Francisco (S.B.), and Stanford Cancer Center, Stanford (S.S.) - both in California; Alliance Statistics and Data Management Center, Mayo Clinic, Scottsdale, AZ (A.C.D.); the University of Hawaii Cancer Center, Honolulu (J.A.); the Alliance Protocol Operations Office, University of Chicago, Chicago (A.S.); Mount Sinai Medical Center (E.M.W.) and Memorial Sloan Kettering Cancer Center (N.R., E.M.O.) - both in New York; Washington University School of Medicine and Siteman Cancer Center, St. Louis (N.A.T.); the University of New Mexico Comprehensive Cancer Center, Albuquerque (B.T.); Fox Chase Cancer Center, Philadelphia (N.V.); M.D. Anderson Cancer Center, Houston (A.D.); Moffitt Cancer Center, Tampa, FL (J.R.S.); and the National Cancer Institute, Bethesda, MD (E.C.K.).

Fang-Shu Ou (FS)

From Dana-Farber Cancer Institute (J.A.C., J.A.M.), Boston Medical Center (M.H.K.), and Boston University (M.H.K.) - all in Boston; the Alliance Statistics and Data Management Center, Mayo Clinic (S.G., T.Z., S.P., F.-S.O.), and Mayo Clinic Comprehensive Cancer Center (T.R.H.) - both in Rochester, MN; Wright Center of Innovation and the Imaging and Radiation Oncology Core, University of Cincinnati, Cincinnati (M.V.K.), and the Ohio State University Comprehensive Cancer Center, Columbus (B.K.) - both in Ohio; the University of California, San Francisco, San Francisco (S.B.), and Stanford Cancer Center, Stanford (S.S.) - both in California; Alliance Statistics and Data Management Center, Mayo Clinic, Scottsdale, AZ (A.C.D.); the University of Hawaii Cancer Center, Honolulu (J.A.); the Alliance Protocol Operations Office, University of Chicago, Chicago (A.S.); Mount Sinai Medical Center (E.M.W.) and Memorial Sloan Kettering Cancer Center (N.R., E.M.O.) - both in New York; Washington University School of Medicine and Siteman Cancer Center, St. Louis (N.A.T.); the University of New Mexico Comprehensive Cancer Center, Albuquerque (B.T.); Fox Chase Cancer Center, Philadelphia (N.V.); M.D. Anderson Cancer Center, Houston (A.D.); Moffitt Cancer Center, Tampa, FL (J.R.S.); and the National Cancer Institute, Bethesda, MD (E.C.K.).

Amylou C Dueck (AC)

From Dana-Farber Cancer Institute (J.A.C., J.A.M.), Boston Medical Center (M.H.K.), and Boston University (M.H.K.) - all in Boston; the Alliance Statistics and Data Management Center, Mayo Clinic (S.G., T.Z., S.P., F.-S.O.), and Mayo Clinic Comprehensive Cancer Center (T.R.H.) - both in Rochester, MN; Wright Center of Innovation and the Imaging and Radiation Oncology Core, University of Cincinnati, Cincinnati (M.V.K.), and the Ohio State University Comprehensive Cancer Center, Columbus (B.K.) - both in Ohio; the University of California, San Francisco, San Francisco (S.B.), and Stanford Cancer Center, Stanford (S.S.) - both in California; Alliance Statistics and Data Management Center, Mayo Clinic, Scottsdale, AZ (A.C.D.); the University of Hawaii Cancer Center, Honolulu (J.A.); the Alliance Protocol Operations Office, University of Chicago, Chicago (A.S.); Mount Sinai Medical Center (E.M.W.) and Memorial Sloan Kettering Cancer Center (N.R., E.M.O.) - both in New York; Washington University School of Medicine and Siteman Cancer Center, St. Louis (N.A.T.); the University of New Mexico Comprehensive Cancer Center, Albuquerque (B.T.); Fox Chase Cancer Center, Philadelphia (N.V.); M.D. Anderson Cancer Center, Houston (A.D.); Moffitt Cancer Center, Tampa, FL (J.R.S.); and the National Cancer Institute, Bethesda, MD (E.C.K.).
ORCID: 0000-0002-9912-1085

Jared Acoba (J)

From Dana-Farber Cancer Institute (J.A.C., J.A.M.), Boston Medical Center (M.H.K.), and Boston University (M.H.K.) - all in Boston; the Alliance Statistics and Data Management Center, Mayo Clinic (S.G., T.Z., S.P., F.-S.O.), and Mayo Clinic Comprehensive Cancer Center (T.R.H.) - both in Rochester, MN; Wright Center of Innovation and the Imaging and Radiation Oncology Core, University of Cincinnati, Cincinnati (M.V.K.), and the Ohio State University Comprehensive Cancer Center, Columbus (B.K.) - both in Ohio; the University of California, San Francisco, San Francisco (S.B.), and Stanford Cancer Center, Stanford (S.S.) - both in California; Alliance Statistics and Data Management Center, Mayo Clinic, Scottsdale, AZ (A.C.D.); the University of Hawaii Cancer Center, Honolulu (J.A.); the Alliance Protocol Operations Office, University of Chicago, Chicago (A.S.); Mount Sinai Medical Center (E.M.W.) and Memorial Sloan Kettering Cancer Center (N.R., E.M.O.) - both in New York; Washington University School of Medicine and Siteman Cancer Center, St. Louis (N.A.T.); the University of New Mexico Comprehensive Cancer Center, Albuquerque (B.T.); Fox Chase Cancer Center, Philadelphia (N.V.); M.D. Anderson Cancer Center, Houston (A.D.); Moffitt Cancer Center, Tampa, FL (J.R.S.); and the National Cancer Institute, Bethesda, MD (E.C.K.).

Ardaman Shergill (A)

From Dana-Farber Cancer Institute (J.A.C., J.A.M.), Boston Medical Center (M.H.K.), and Boston University (M.H.K.) - all in Boston; the Alliance Statistics and Data Management Center, Mayo Clinic (S.G., T.Z., S.P., F.-S.O.), and Mayo Clinic Comprehensive Cancer Center (T.R.H.) - both in Rochester, MN; Wright Center of Innovation and the Imaging and Radiation Oncology Core, University of Cincinnati, Cincinnati (M.V.K.), and the Ohio State University Comprehensive Cancer Center, Columbus (B.K.) - both in Ohio; the University of California, San Francisco, San Francisco (S.B.), and Stanford Cancer Center, Stanford (S.S.) - both in California; Alliance Statistics and Data Management Center, Mayo Clinic, Scottsdale, AZ (A.C.D.); the University of Hawaii Cancer Center, Honolulu (J.A.); the Alliance Protocol Operations Office, University of Chicago, Chicago (A.S.); Mount Sinai Medical Center (E.M.W.) and Memorial Sloan Kettering Cancer Center (N.R., E.M.O.) - both in New York; Washington University School of Medicine and Siteman Cancer Center, St. Louis (N.A.T.); the University of New Mexico Comprehensive Cancer Center, Albuquerque (B.T.); Fox Chase Cancer Center, Philadelphia (N.V.); M.D. Anderson Cancer Center, Houston (A.D.); Moffitt Cancer Center, Tampa, FL (J.R.S.); and the National Cancer Institute, Bethesda, MD (E.C.K.).

Edward M Wolin (EM)

From Dana-Farber Cancer Institute (J.A.C., J.A.M.), Boston Medical Center (M.H.K.), and Boston University (M.H.K.) - all in Boston; the Alliance Statistics and Data Management Center, Mayo Clinic (S.G., T.Z., S.P., F.-S.O.), and Mayo Clinic Comprehensive Cancer Center (T.R.H.) - both in Rochester, MN; Wright Center of Innovation and the Imaging and Radiation Oncology Core, University of Cincinnati, Cincinnati (M.V.K.), and the Ohio State University Comprehensive Cancer Center, Columbus (B.K.) - both in Ohio; the University of California, San Francisco, San Francisco (S.B.), and Stanford Cancer Center, Stanford (S.S.) - both in California; Alliance Statistics and Data Management Center, Mayo Clinic, Scottsdale, AZ (A.C.D.); the University of Hawaii Cancer Center, Honolulu (J.A.); the Alliance Protocol Operations Office, University of Chicago, Chicago (A.S.); Mount Sinai Medical Center (E.M.W.) and Memorial Sloan Kettering Cancer Center (N.R., E.M.O.) - both in New York; Washington University School of Medicine and Siteman Cancer Center, St. Louis (N.A.T.); the University of New Mexico Comprehensive Cancer Center, Albuquerque (B.T.); Fox Chase Cancer Center, Philadelphia (N.V.); M.D. Anderson Cancer Center, Houston (A.D.); Moffitt Cancer Center, Tampa, FL (J.R.S.); and the National Cancer Institute, Bethesda, MD (E.C.K.).

Thorvardur R Halfdanarson (TR)

From Dana-Farber Cancer Institute (J.A.C., J.A.M.), Boston Medical Center (M.H.K.), and Boston University (M.H.K.) - all in Boston; the Alliance Statistics and Data Management Center, Mayo Clinic (S.G., T.Z., S.P., F.-S.O.), and Mayo Clinic Comprehensive Cancer Center (T.R.H.) - both in Rochester, MN; Wright Center of Innovation and the Imaging and Radiation Oncology Core, University of Cincinnati, Cincinnati (M.V.K.), and the Ohio State University Comprehensive Cancer Center, Columbus (B.K.) - both in Ohio; the University of California, San Francisco, San Francisco (S.B.), and Stanford Cancer Center, Stanford (S.S.) - both in California; Alliance Statistics and Data Management Center, Mayo Clinic, Scottsdale, AZ (A.C.D.); the University of Hawaii Cancer Center, Honolulu (J.A.); the Alliance Protocol Operations Office, University of Chicago, Chicago (A.S.); Mount Sinai Medical Center (E.M.W.) and Memorial Sloan Kettering Cancer Center (N.R., E.M.O.) - both in New York; Washington University School of Medicine and Siteman Cancer Center, St. Louis (N.A.T.); the University of New Mexico Comprehensive Cancer Center, Albuquerque (B.T.); Fox Chase Cancer Center, Philadelphia (N.V.); M.D. Anderson Cancer Center, Houston (A.D.); Moffitt Cancer Center, Tampa, FL (J.R.S.); and the National Cancer Institute, Bethesda, MD (E.C.K.).

Bhavana Konda (B)

From Dana-Farber Cancer Institute (J.A.C., J.A.M.), Boston Medical Center (M.H.K.), and Boston University (M.H.K.) - all in Boston; the Alliance Statistics and Data Management Center, Mayo Clinic (S.G., T.Z., S.P., F.-S.O.), and Mayo Clinic Comprehensive Cancer Center (T.R.H.) - both in Rochester, MN; Wright Center of Innovation and the Imaging and Radiation Oncology Core, University of Cincinnati, Cincinnati (M.V.K.), and the Ohio State University Comprehensive Cancer Center, Columbus (B.K.) - both in Ohio; the University of California, San Francisco, San Francisco (S.B.), and Stanford Cancer Center, Stanford (S.S.) - both in California; Alliance Statistics and Data Management Center, Mayo Clinic, Scottsdale, AZ (A.C.D.); the University of Hawaii Cancer Center, Honolulu (J.A.); the Alliance Protocol Operations Office, University of Chicago, Chicago (A.S.); Mount Sinai Medical Center (E.M.W.) and Memorial Sloan Kettering Cancer Center (N.R., E.M.O.) - both in New York; Washington University School of Medicine and Siteman Cancer Center, St. Louis (N.A.T.); the University of New Mexico Comprehensive Cancer Center, Albuquerque (B.T.); Fox Chase Cancer Center, Philadelphia (N.V.); M.D. Anderson Cancer Center, Houston (A.D.); Moffitt Cancer Center, Tampa, FL (J.R.S.); and the National Cancer Institute, Bethesda, MD (E.C.K.).

Nikolaos A Trikalinos (NA)

From Dana-Farber Cancer Institute (J.A.C., J.A.M.), Boston Medical Center (M.H.K.), and Boston University (M.H.K.) - all in Boston; the Alliance Statistics and Data Management Center, Mayo Clinic (S.G., T.Z., S.P., F.-S.O.), and Mayo Clinic Comprehensive Cancer Center (T.R.H.) - both in Rochester, MN; Wright Center of Innovation and the Imaging and Radiation Oncology Core, University of Cincinnati, Cincinnati (M.V.K.), and the Ohio State University Comprehensive Cancer Center, Columbus (B.K.) - both in Ohio; the University of California, San Francisco, San Francisco (S.B.), and Stanford Cancer Center, Stanford (S.S.) - both in California; Alliance Statistics and Data Management Center, Mayo Clinic, Scottsdale, AZ (A.C.D.); the University of Hawaii Cancer Center, Honolulu (J.A.); the Alliance Protocol Operations Office, University of Chicago, Chicago (A.S.); Mount Sinai Medical Center (E.M.W.) and Memorial Sloan Kettering Cancer Center (N.R., E.M.O.) - both in New York; Washington University School of Medicine and Siteman Cancer Center, St. Louis (N.A.T.); the University of New Mexico Comprehensive Cancer Center, Albuquerque (B.T.); Fox Chase Cancer Center, Philadelphia (N.V.); M.D. Anderson Cancer Center, Houston (A.D.); Moffitt Cancer Center, Tampa, FL (J.R.S.); and the National Cancer Institute, Bethesda, MD (E.C.K.).

Bernard Tawfik (B)

From Dana-Farber Cancer Institute (J.A.C., J.A.M.), Boston Medical Center (M.H.K.), and Boston University (M.H.K.) - all in Boston; the Alliance Statistics and Data Management Center, Mayo Clinic (S.G., T.Z., S.P., F.-S.O.), and Mayo Clinic Comprehensive Cancer Center (T.R.H.) - both in Rochester, MN; Wright Center of Innovation and the Imaging and Radiation Oncology Core, University of Cincinnati, Cincinnati (M.V.K.), and the Ohio State University Comprehensive Cancer Center, Columbus (B.K.) - both in Ohio; the University of California, San Francisco, San Francisco (S.B.), and Stanford Cancer Center, Stanford (S.S.) - both in California; Alliance Statistics and Data Management Center, Mayo Clinic, Scottsdale, AZ (A.C.D.); the University of Hawaii Cancer Center, Honolulu (J.A.); the Alliance Protocol Operations Office, University of Chicago, Chicago (A.S.); Mount Sinai Medical Center (E.M.W.) and Memorial Sloan Kettering Cancer Center (N.R., E.M.O.) - both in New York; Washington University School of Medicine and Siteman Cancer Center, St. Louis (N.A.T.); the University of New Mexico Comprehensive Cancer Center, Albuquerque (B.T.); Fox Chase Cancer Center, Philadelphia (N.V.); M.D. Anderson Cancer Center, Houston (A.D.); Moffitt Cancer Center, Tampa, FL (J.R.S.); and the National Cancer Institute, Bethesda, MD (E.C.K.).

Nitya Raj (N)

From Dana-Farber Cancer Institute (J.A.C., J.A.M.), Boston Medical Center (M.H.K.), and Boston University (M.H.K.) - all in Boston; the Alliance Statistics and Data Management Center, Mayo Clinic (S.G., T.Z., S.P., F.-S.O.), and Mayo Clinic Comprehensive Cancer Center (T.R.H.) - both in Rochester, MN; Wright Center of Innovation and the Imaging and Radiation Oncology Core, University of Cincinnati, Cincinnati (M.V.K.), and the Ohio State University Comprehensive Cancer Center, Columbus (B.K.) - both in Ohio; the University of California, San Francisco, San Francisco (S.B.), and Stanford Cancer Center, Stanford (S.S.) - both in California; Alliance Statistics and Data Management Center, Mayo Clinic, Scottsdale, AZ (A.C.D.); the University of Hawaii Cancer Center, Honolulu (J.A.); the Alliance Protocol Operations Office, University of Chicago, Chicago (A.S.); Mount Sinai Medical Center (E.M.W.) and Memorial Sloan Kettering Cancer Center (N.R., E.M.O.) - both in New York; Washington University School of Medicine and Siteman Cancer Center, St. Louis (N.A.T.); the University of New Mexico Comprehensive Cancer Center, Albuquerque (B.T.); Fox Chase Cancer Center, Philadelphia (N.V.); M.D. Anderson Cancer Center, Houston (A.D.); Moffitt Cancer Center, Tampa, FL (J.R.S.); and the National Cancer Institute, Bethesda, MD (E.C.K.).

Shagufta Shaheen (S)

From Dana-Farber Cancer Institute (J.A.C., J.A.M.), Boston Medical Center (M.H.K.), and Boston University (M.H.K.) - all in Boston; the Alliance Statistics and Data Management Center, Mayo Clinic (S.G., T.Z., S.P., F.-S.O.), and Mayo Clinic Comprehensive Cancer Center (T.R.H.) - both in Rochester, MN; Wright Center of Innovation and the Imaging and Radiation Oncology Core, University of Cincinnati, Cincinnati (M.V.K.), and the Ohio State University Comprehensive Cancer Center, Columbus (B.K.) - both in Ohio; the University of California, San Francisco, San Francisco (S.B.), and Stanford Cancer Center, Stanford (S.S.) - both in California; Alliance Statistics and Data Management Center, Mayo Clinic, Scottsdale, AZ (A.C.D.); the University of Hawaii Cancer Center, Honolulu (J.A.); the Alliance Protocol Operations Office, University of Chicago, Chicago (A.S.); Mount Sinai Medical Center (E.M.W.) and Memorial Sloan Kettering Cancer Center (N.R., E.M.O.) - both in New York; Washington University School of Medicine and Siteman Cancer Center, St. Louis (N.A.T.); the University of New Mexico Comprehensive Cancer Center, Albuquerque (B.T.); Fox Chase Cancer Center, Philadelphia (N.V.); M.D. Anderson Cancer Center, Houston (A.D.); Moffitt Cancer Center, Tampa, FL (J.R.S.); and the National Cancer Institute, Bethesda, MD (E.C.K.).

Namrata Vijayvergia (N)

From Dana-Farber Cancer Institute (J.A.C., J.A.M.), Boston Medical Center (M.H.K.), and Boston University (M.H.K.) - all in Boston; the Alliance Statistics and Data Management Center, Mayo Clinic (S.G., T.Z., S.P., F.-S.O.), and Mayo Clinic Comprehensive Cancer Center (T.R.H.) - both in Rochester, MN; Wright Center of Innovation and the Imaging and Radiation Oncology Core, University of Cincinnati, Cincinnati (M.V.K.), and the Ohio State University Comprehensive Cancer Center, Columbus (B.K.) - both in Ohio; the University of California, San Francisco, San Francisco (S.B.), and Stanford Cancer Center, Stanford (S.S.) - both in California; Alliance Statistics and Data Management Center, Mayo Clinic, Scottsdale, AZ (A.C.D.); the University of Hawaii Cancer Center, Honolulu (J.A.); the Alliance Protocol Operations Office, University of Chicago, Chicago (A.S.); Mount Sinai Medical Center (E.M.W.) and Memorial Sloan Kettering Cancer Center (N.R., E.M.O.) - both in New York; Washington University School of Medicine and Siteman Cancer Center, St. Louis (N.A.T.); the University of New Mexico Comprehensive Cancer Center, Albuquerque (B.T.); Fox Chase Cancer Center, Philadelphia (N.V.); M.D. Anderson Cancer Center, Houston (A.D.); Moffitt Cancer Center, Tampa, FL (J.R.S.); and the National Cancer Institute, Bethesda, MD (E.C.K.).

Arvind Dasari (A)

From Dana-Farber Cancer Institute (J.A.C., J.A.M.), Boston Medical Center (M.H.K.), and Boston University (M.H.K.) - all in Boston; the Alliance Statistics and Data Management Center, Mayo Clinic (S.G., T.Z., S.P., F.-S.O.), and Mayo Clinic Comprehensive Cancer Center (T.R.H.) - both in Rochester, MN; Wright Center of Innovation and the Imaging and Radiation Oncology Core, University of Cincinnati, Cincinnati (M.V.K.), and the Ohio State University Comprehensive Cancer Center, Columbus (B.K.) - both in Ohio; the University of California, San Francisco, San Francisco (S.B.), and Stanford Cancer Center, Stanford (S.S.) - both in California; Alliance Statistics and Data Management Center, Mayo Clinic, Scottsdale, AZ (A.C.D.); the University of Hawaii Cancer Center, Honolulu (J.A.); the Alliance Protocol Operations Office, University of Chicago, Chicago (A.S.); Mount Sinai Medical Center (E.M.W.) and Memorial Sloan Kettering Cancer Center (N.R., E.M.O.) - both in New York; Washington University School of Medicine and Siteman Cancer Center, St. Louis (N.A.T.); the University of New Mexico Comprehensive Cancer Center, Albuquerque (B.T.); Fox Chase Cancer Center, Philadelphia (N.V.); M.D. Anderson Cancer Center, Houston (A.D.); Moffitt Cancer Center, Tampa, FL (J.R.S.); and the National Cancer Institute, Bethesda, MD (E.C.K.).

Jonathan R Strosberg (JR)

From Dana-Farber Cancer Institute (J.A.C., J.A.M.), Boston Medical Center (M.H.K.), and Boston University (M.H.K.) - all in Boston; the Alliance Statistics and Data Management Center, Mayo Clinic (S.G., T.Z., S.P., F.-S.O.), and Mayo Clinic Comprehensive Cancer Center (T.R.H.) - both in Rochester, MN; Wright Center of Innovation and the Imaging and Radiation Oncology Core, University of Cincinnati, Cincinnati (M.V.K.), and the Ohio State University Comprehensive Cancer Center, Columbus (B.K.) - both in Ohio; the University of California, San Francisco, San Francisco (S.B.), and Stanford Cancer Center, Stanford (S.S.) - both in California; Alliance Statistics and Data Management Center, Mayo Clinic, Scottsdale, AZ (A.C.D.); the University of Hawaii Cancer Center, Honolulu (J.A.); the Alliance Protocol Operations Office, University of Chicago, Chicago (A.S.); Mount Sinai Medical Center (E.M.W.) and Memorial Sloan Kettering Cancer Center (N.R., E.M.O.) - both in New York; Washington University School of Medicine and Siteman Cancer Center, St. Louis (N.A.T.); the University of New Mexico Comprehensive Cancer Center, Albuquerque (B.T.); Fox Chase Cancer Center, Philadelphia (N.V.); M.D. Anderson Cancer Center, Houston (A.D.); Moffitt Cancer Center, Tampa, FL (J.R.S.); and the National Cancer Institute, Bethesda, MD (E.C.K.).
ORCID: 0000-0001-8405-218X

Elise C Kohn (EC)

From Dana-Farber Cancer Institute (J.A.C., J.A.M.), Boston Medical Center (M.H.K.), and Boston University (M.H.K.) - all in Boston; the Alliance Statistics and Data Management Center, Mayo Clinic (S.G., T.Z., S.P., F.-S.O.), and Mayo Clinic Comprehensive Cancer Center (T.R.H.) - both in Rochester, MN; Wright Center of Innovation and the Imaging and Radiation Oncology Core, University of Cincinnati, Cincinnati (M.V.K.), and the Ohio State University Comprehensive Cancer Center, Columbus (B.K.) - both in Ohio; the University of California, San Francisco, San Francisco (S.B.), and Stanford Cancer Center, Stanford (S.S.) - both in California; Alliance Statistics and Data Management Center, Mayo Clinic, Scottsdale, AZ (A.C.D.); the University of Hawaii Cancer Center, Honolulu (J.A.); the Alliance Protocol Operations Office, University of Chicago, Chicago (A.S.); Mount Sinai Medical Center (E.M.W.) and Memorial Sloan Kettering Cancer Center (N.R., E.M.O.) - both in New York; Washington University School of Medicine and Siteman Cancer Center, St. Louis (N.A.T.); the University of New Mexico Comprehensive Cancer Center, Albuquerque (B.T.); Fox Chase Cancer Center, Philadelphia (N.V.); M.D. Anderson Cancer Center, Houston (A.D.); Moffitt Cancer Center, Tampa, FL (J.R.S.); and the National Cancer Institute, Bethesda, MD (E.C.K.).

Matthew H Kulke (MH)

From Dana-Farber Cancer Institute (J.A.C., J.A.M.), Boston Medical Center (M.H.K.), and Boston University (M.H.K.) - all in Boston; the Alliance Statistics and Data Management Center, Mayo Clinic (S.G., T.Z., S.P., F.-S.O.), and Mayo Clinic Comprehensive Cancer Center (T.R.H.) - both in Rochester, MN; Wright Center of Innovation and the Imaging and Radiation Oncology Core, University of Cincinnati, Cincinnati (M.V.K.), and the Ohio State University Comprehensive Cancer Center, Columbus (B.K.) - both in Ohio; the University of California, San Francisco, San Francisco (S.B.), and Stanford Cancer Center, Stanford (S.S.) - both in California; Alliance Statistics and Data Management Center, Mayo Clinic, Scottsdale, AZ (A.C.D.); the University of Hawaii Cancer Center, Honolulu (J.A.); the Alliance Protocol Operations Office, University of Chicago, Chicago (A.S.); Mount Sinai Medical Center (E.M.W.) and Memorial Sloan Kettering Cancer Center (N.R., E.M.O.) - both in New York; Washington University School of Medicine and Siteman Cancer Center, St. Louis (N.A.T.); the University of New Mexico Comprehensive Cancer Center, Albuquerque (B.T.); Fox Chase Cancer Center, Philadelphia (N.V.); M.D. Anderson Cancer Center, Houston (A.D.); Moffitt Cancer Center, Tampa, FL (J.R.S.); and the National Cancer Institute, Bethesda, MD (E.C.K.).

Eileen M O'Reilly (EM)

From Dana-Farber Cancer Institute (J.A.C., J.A.M.), Boston Medical Center (M.H.K.), and Boston University (M.H.K.) - all in Boston; the Alliance Statistics and Data Management Center, Mayo Clinic (S.G., T.Z., S.P., F.-S.O.), and Mayo Clinic Comprehensive Cancer Center (T.R.H.) - both in Rochester, MN; Wright Center of Innovation and the Imaging and Radiation Oncology Core, University of Cincinnati, Cincinnati (M.V.K.), and the Ohio State University Comprehensive Cancer Center, Columbus (B.K.) - both in Ohio; the University of California, San Francisco, San Francisco (S.B.), and Stanford Cancer Center, Stanford (S.S.) - both in California; Alliance Statistics and Data Management Center, Mayo Clinic, Scottsdale, AZ (A.C.D.); the University of Hawaii Cancer Center, Honolulu (J.A.); the Alliance Protocol Operations Office, University of Chicago, Chicago (A.S.); Mount Sinai Medical Center (E.M.W.) and Memorial Sloan Kettering Cancer Center (N.R., E.M.O.) - both in New York; Washington University School of Medicine and Siteman Cancer Center, St. Louis (N.A.T.); the University of New Mexico Comprehensive Cancer Center, Albuquerque (B.T.); Fox Chase Cancer Center, Philadelphia (N.V.); M.D. Anderson Cancer Center, Houston (A.D.); Moffitt Cancer Center, Tampa, FL (J.R.S.); and the National Cancer Institute, Bethesda, MD (E.C.K.).

Jeffrey A Meyerhardt (JA)

From Dana-Farber Cancer Institute (J.A.C., J.A.M.), Boston Medical Center (M.H.K.), and Boston University (M.H.K.) - all in Boston; the Alliance Statistics and Data Management Center, Mayo Clinic (S.G., T.Z., S.P., F.-S.O.), and Mayo Clinic Comprehensive Cancer Center (T.R.H.) - both in Rochester, MN; Wright Center of Innovation and the Imaging and Radiation Oncology Core, University of Cincinnati, Cincinnati (M.V.K.), and the Ohio State University Comprehensive Cancer Center, Columbus (B.K.) - both in Ohio; the University of California, San Francisco, San Francisco (S.B.), and Stanford Cancer Center, Stanford (S.S.) - both in California; Alliance Statistics and Data Management Center, Mayo Clinic, Scottsdale, AZ (A.C.D.); the University of Hawaii Cancer Center, Honolulu (J.A.); the Alliance Protocol Operations Office, University of Chicago, Chicago (A.S.); Mount Sinai Medical Center (E.M.W.) and Memorial Sloan Kettering Cancer Center (N.R., E.M.O.) - both in New York; Washington University School of Medicine and Siteman Cancer Center, St. Louis (N.A.T.); the University of New Mexico Comprehensive Cancer Center, Albuquerque (B.T.); Fox Chase Cancer Center, Philadelphia (N.V.); M.D. Anderson Cancer Center, Houston (A.D.); Moffitt Cancer Center, Tampa, FL (J.R.S.); and the National Cancer Institute, Bethesda, MD (E.C.K.).

Classifications MeSH