Chemotherapy With or Without Maintenance Sunitinib for Untreated Extensive-Stage Small-Cell Lung Cancer: A Randomized, Double-Blind, Placebo-Controlled Phase II Study-CALGB 30504 (Alliance).
OBJECTIVE
To evaluate the efficacy of maintenance sunitinib after chemotherapy for small-cell lung cancer (SCLC).


METHODS
The Cancer and Leukemia Group B 30504 trial was a randomized, placebo-controlled, phase II study that enrolled patients before chemotherapy (cisplatin 80 mg/m(2) or carboplatin area under the curve of 5 on day 1 plus etoposide 100 mg/m(2) per day on days 1 to 3 every 21 days for four to six cycles). Patients without progression were randomly assigned 1:1 to placebo or sunitinib 37.5 mg per day until progression. Cross-over after progression was allowed. The primary end point was progression-free survival (PFS) from random assignment for maintenance placebo versus sunitinib using a one-sided log-rank test with α = .15; 80 randomly assigned patients provided 89% power to detect a hazard ratio (HR) of 1.67.


RESULTS
One hundred forty-four patients were enrolled; 138 patients received chemotherapy. Ninety-five patients were randomly assigned; 10 patients did not receive maintenance therapy (five on each arm). Eighty-five patients received maintenance therapy (placebo, n = 41; sunitinib, n = 44). Grade 3 adverse events with more than 5% incidence were fatigue (19%), decreased neutrophils (14%), decreased leukocytes (7%), and decreased platelets (7%) for sunitinib and fatigue (10%) for placebo; grade 4 adverse events were GI hemorrhage (n = 1) and pancreatitis, hypocalcemia, and elevated lipase (n = 1; all in same patient) for sunitinib and thrombocytopenia (n = 1) and hypernatremia (n = 1) for placebo. Median PFS on maintenance was 2.1 months for placebo and 3.7 months for sunitinib (HR, 1.62; 70% CI, 1.27 to 2.08; 95% CI, 1.02 to 2.60; one-sided P = .02). Median overall survival from random assignment was 6.9 months for placebo and 9.0 months for sunitinib (HR, 1.28; 95% CI, 0.79 to 2.10; one-sided P = .16). Three sunitinib and no placebo patients achieved complete response during maintenance. Ten (77%) of 13 patients evaluable after cross-over had stable disease on sunitinib (6 to 27 weeks).


CONCLUSIONS
Maintenance sunitinib was safe and improved PFS in extensive-stage SCLC.
Neal E. Ready and Jeffrey Crawford, Duke University Medical Center; Herbert H. Pang and Lin Gu, Alliance Statistics and Data Center, Duke University Medical Center, Durham; Antonius A. Miller, Wake Forest University Medical Center, Winston Salem, NC; Gregory A. Otterson, Ohio State University Medical Center, Columbus, OH; Sachdev P. Thomas, Illinois Oncology Research Association Community Clinical Oncology Program, Illinois Cancer Care, Peoria; Everett E. Vokes, University of Chicago, Chicago, IL; Maria Baggstrom, Washington University School of Medicine, St Louis, MO; Gregory A. Masters, Christiana Healthcare Services, Christiana Hospital, Newark, DE; Stephen L. Graziano and Jeffrey Bogart, State University of New York Upstate Medical University, Syracuse, NY. ready001@mc.duke.edu.
Neal E
NE
Ready
Neal E. Ready and Jeffrey Crawford, Duke University Medical Center; Herbert H. Pang and Lin Gu, Alliance Statistics and Data Center, Duke University Medical Center, Durham; Antonius A. Miller, Wake Forest University Medical Center, Winston Salem, NC; Gregory A. Otterson, Ohio State University Medical Center, Columbus, OH; Sachdev P. Thomas, Illinois Oncology Research Association Community Clinical Oncology Program, Illinois Cancer Care, Peoria; Everett E. Vokes, University of Chicago, Chicago, IL; Maria Baggstrom, Washington University School of Medicine, St Louis, MO; Gregory A. Masters, Christiana Healthcare Services, Christiana Hospital, Newark, DE; Stephen L. Graziano and Jeffrey Bogart, State University of New York Upstate Medical University, Syracuse, NY.
Herbert H
HH
Pang
Neal E. Ready and Jeffrey Crawford, Duke University Medical Center; Herbert H. Pang and Lin Gu, Alliance Statistics and Data Center, Duke University Medical Center, Durham; Antonius A. Miller, Wake Forest University Medical Center, Winston Salem, NC; Gregory A. Otterson, Ohio State University Medical Center, Columbus, OH; Sachdev P. Thomas, Illinois Oncology Research Association Community Clinical Oncology Program, Illinois Cancer Care, Peoria; Everett E. Vokes, University of Chicago, Chicago, IL; Maria Baggstrom, Washington University School of Medicine, St Louis, MO; Gregory A. Masters, Christiana Healthcare Services, Christiana Hospital, Newark, DE; Stephen L. Graziano and Jeffrey Bogart, State University of New York Upstate Medical University, Syracuse, NY.
Lin
L
Gu
Neal E. Ready and Jeffrey Crawford, Duke University Medical Center; Herbert H. Pang and Lin Gu, Alliance Statistics and Data Center, Duke University Medical Center, Durham; Antonius A. Miller, Wake Forest University Medical Center, Winston Salem, NC; Gregory A. Otterson, Ohio State University Medical Center, Columbus, OH; Sachdev P. Thomas, Illinois Oncology Research Association Community Clinical Oncology Program, Illinois Cancer Care, Peoria; Everett E. Vokes, University of Chicago, Chicago, IL; Maria Baggstrom, Washington University School of Medicine, St Louis, MO; Gregory A. Masters, Christiana Healthcare Services, Christiana Hospital, Newark, DE; Stephen L. Graziano and Jeffrey Bogart, State University of New York Upstate Medical University, Syracuse, NY.
Gregory A
GA
Otterson
Neal E. Ready and Jeffrey Crawford, Duke University Medical Center; Herbert H. Pang and Lin Gu, Alliance Statistics and Data Center, Duke University Medical Center, Durham; Antonius A. Miller, Wake Forest University Medical Center, Winston Salem, NC; Gregory A. Otterson, Ohio State University Medical Center, Columbus, OH; Sachdev P. Thomas, Illinois Oncology Research Association Community Clinical Oncology Program, Illinois Cancer Care, Peoria; Everett E. Vokes, University of Chicago, Chicago, IL; Maria Baggstrom, Washington University School of Medicine, St Louis, MO; Gregory A. Masters, Christiana Healthcare Services, Christiana Hospital, Newark, DE; Stephen L. Graziano and Jeffrey Bogart, State University of New York Upstate Medical University, Syracuse, NY.
Sachdev P
SP
Thomas
Neal E. Ready and Jeffrey Crawford, Duke University Medical Center; Herbert H. Pang and Lin Gu, Alliance Statistics and Data Center, Duke University Medical Center, Durham; Antonius A. Miller, Wake Forest University Medical Center, Winston Salem, NC; Gregory A. Otterson, Ohio State University Medical Center, Columbus, OH; Sachdev P. Thomas, Illinois Oncology Research Association Community Clinical Oncology Program, Illinois Cancer Care, Peoria; Everett E. Vokes, University of Chicago, Chicago, IL; Maria Baggstrom, Washington University School of Medicine, St Louis, MO; Gregory A. Masters, Christiana Healthcare Services, Christiana Hospital, Newark, DE; Stephen L. Graziano and Jeffrey Bogart, State University of New York Upstate Medical University, Syracuse, NY.
Antonius A
AA
Miller
Neal E. Ready and Jeffrey Crawford, Duke University Medical Center; Herbert H. Pang and Lin Gu, Alliance Statistics and Data Center, Duke University Medical Center, Durham; Antonius A. Miller, Wake Forest University Medical Center, Winston Salem, NC; Gregory A. Otterson, Ohio State University Medical Center, Columbus, OH; Sachdev P. Thomas, Illinois Oncology Research Association Community Clinical Oncology Program, Illinois Cancer Care, Peoria; Everett E. Vokes, University of Chicago, Chicago, IL; Maria Baggstrom, Washington University School of Medicine, St Louis, MO; Gregory A. Masters, Christiana Healthcare Services, Christiana Hospital, Newark, DE; Stephen L. Graziano and Jeffrey Bogart, State University of New York Upstate Medical University, Syracuse, NY.
Maria
M
Baggstrom
Neal E. Ready and Jeffrey Crawford, Duke University Medical Center; Herbert H. Pang and Lin Gu, Alliance Statistics and Data Center, Duke University Medical Center, Durham; Antonius A. Miller, Wake Forest University Medical Center, Winston Salem, NC; Gregory A. Otterson, Ohio State University Medical Center, Columbus, OH; Sachdev P. Thomas, Illinois Oncology Research Association Community Clinical Oncology Program, Illinois Cancer Care, Peoria; Everett E. Vokes, University of Chicago, Chicago, IL; Maria Baggstrom, Washington University School of Medicine, St Louis, MO; Gregory A. Masters, Christiana Healthcare Services, Christiana Hospital, Newark, DE; Stephen L. Graziano and Jeffrey Bogart, State University of New York Upstate Medical University, Syracuse, NY.
Gregory A
GA
Masters
Neal E. Ready and Jeffrey Crawford, Duke University Medical Center; Herbert H. Pang and Lin Gu, Alliance Statistics and Data Center, Duke University Medical Center, Durham; Antonius A. Miller, Wake Forest University Medical Center, Winston Salem, NC; Gregory A. Otterson, Ohio State University Medical Center, Columbus, OH; Sachdev P. Thomas, Illinois Oncology Research Association Community Clinical Oncology Program, Illinois Cancer Care, Peoria; Everett E. Vokes, University of Chicago, Chicago, IL; Maria Baggstrom, Washington University School of Medicine, St Louis, MO; Gregory A. Masters, Christiana Healthcare Services, Christiana Hospital, Newark, DE; Stephen L. Graziano and Jeffrey Bogart, State University of New York Upstate Medical University, Syracuse, NY.
Stephen L
SL
Graziano
Neal E. Ready and Jeffrey Crawford, Duke University Medical Center; Herbert H. Pang and Lin Gu, Alliance Statistics and Data Center, Duke University Medical Center, Durham; Antonius A. Miller, Wake Forest University Medical Center, Winston Salem, NC; Gregory A. Otterson, Ohio State University Medical Center, Columbus, OH; Sachdev P. Thomas, Illinois Oncology Research Association Community Clinical Oncology Program, Illinois Cancer Care, Peoria; Everett E. Vokes, University of Chicago, Chicago, IL; Maria Baggstrom, Washington University School of Medicine, St Louis, MO; Gregory A. Masters, Christiana Healthcare Services, Christiana Hospital, Newark, DE; Stephen L. Graziano and Jeffrey Bogart, State University of New York Upstate Medical University, Syracuse, NY.
Jeffrey
J
Crawford
Neal E. Ready and Jeffrey Crawford, Duke University Medical Center; Herbert H. Pang and Lin Gu, Alliance Statistics and Data Center, Duke University Medical Center, Durham; Antonius A. Miller, Wake Forest University Medical Center, Winston Salem, NC; Gregory A. Otterson, Ohio State University Medical Center, Columbus, OH; Sachdev P. Thomas, Illinois Oncology Research Association Community Clinical Oncology Program, Illinois Cancer Care, Peoria; Everett E. Vokes, University of Chicago, Chicago, IL; Maria Baggstrom, Washington University School of Medicine, St Louis, MO; Gregory A. Masters, Christiana Healthcare Services, Christiana Hospital, Newark, DE; Stephen L. Graziano and Jeffrey Bogart, State University of New York Upstate Medical University, Syracuse, NY.
Jeffrey
J
Bogart
Neal E. Ready and Jeffrey Crawford, Duke University Medical Center; Herbert H. Pang and Lin Gu, Alliance Statistics and Data Center, Duke University Medical Center, Durham; Antonius A. Miller, Wake Forest University Medical Center, Winston Salem, NC; Gregory A. Otterson, Ohio State University Medical Center, Columbus, OH; Sachdev P. Thomas, Illinois Oncology Research Association Community Clinical Oncology Program, Illinois Cancer Care, Peoria; Everett E. Vokes, University of Chicago, Chicago, IL; Maria Baggstrom, Washington University School of Medicine, St Louis, MO; Gregory A. Masters, Christiana Healthcare Services, Christiana Hospital, Newark, DE; Stephen L. Graziano and Jeffrey Bogart, State University of New York Upstate Medical University, Syracuse, NY.
Everett E
EE
Vokes
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011758:Pyrroles / Q000008:administration & dosage*; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000401:mortality; D000077210:Sunitinib; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D005047:Etoposide; D016190:Carboplatin; D002945:Cisplatin; D000077210:Sunitinib