Bevacizumab maintenance in patients with advanced non-small-cell lung cancer, clinical patterns, and outcomes in the Eastern Cooperative Oncology Group 4599 Study: results of an exploratory analysis.
BACKGROUND
The Eastern Cooperative Oncology Group (ECOG) 4599 study showed a significant survival benefit with the use of bevacizumab (BV) in combination with carboplatin and paclitaxel (CP) in comparison with CP chemotherapy alone in patients with previously untreated advanced, metastatic or recurrent non-small-cell lung cancer (NSCLC). Such results were achieved using BV as maintenance therapy until progressive disease. Because current data on single-agent BV maintenance in non-small-cell lung cancer are limited, we present a retrospective analysis of safety and efficacy outcomes for patients who received maintenance BV after induction treatment and the maintenance-eligible population of the control arm in ECOG 4599.


METHODS
Landmark analyses were conducted in patients in both the CP and CP+BV groups who were alive and progression free through the completion of six cycles + 21 days. The BV maintenance population consisted of patients in the CP+BV arm, who were alive without progressive disease before the start of maintenance (maintenance-nonprogressor population). CP nonprogressors were those patients in the CP-alone arm without progressive disease after six cycles of CP + 21 days.


RESULTS
Two hundred and seventeen patients (51%) were alive, progression free, and eligible for maintenance therapy six cycles + 21 days after induction CP+ BV compared with 134 patients (30%) in the CP-alone arm. Postinduction progression-free survival was significantly longer in the BV maintenance group relative to CP nonprogressors (4.4 versus 2.8 months; hazards ratio [HR] 0.64; p < 0.001). One-year overall survival rates were 75% for the BV maintenance group versus 69% in the CP nonprogressor group. Two-year overall survival rates were 34% for the BV maintenance group versus 25% in the CP nonprogressor group. Median postinduction overall survival (OS) was also significantly longer for the BV-maintenance group compared with CP nonprogressors (12.8 versus 11.4 months; HR 0.75; p = 0.030). Within the subgroup having complete response or partial response after induction, the progression-free survival and OS hazard ratio estimates were 0.59 (95% [confidence interval] CI: 0.41-0.84) and 0.78 (95% CI: 0.53-1.14), respectively. In the maintenance setting, BV was associated with a less-than 1% rate of grade 3 or 4 hematological toxicities, no grade 3 or 4 nausea, vomiting or diarrhea, and no grade 5 toxicities.


CONCLUSIONS
In this retrospective analysis of patients in the ECOG 4599 study, who were alive, progression free, and on-study 21 days after six cycles of induction therapy, significant reductions in HRs for progression (0.64, p < 0.001) and survival (0.75, p = 0.03) were associated with BV treatment during induction and maintenance compared with CP induction therapy alone and suggestive of possible benefit because of bevacizumab maintenance.
Oregon Health and Science University, Knight Cancer Institute, Portland, OR, USA.
Ariel
A
Lopez-Chavez
Todd
T
Young
Sophie
S
Fages
Larry
L
Leon
Joan H
JH
Schiller
Afshin
A
Dowlati
Julie R
JR
Brahmer
David H
DH
Johnson
Alan
A
Sandler
D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D019468:Disease Management; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D012074:Remission Induction; D012189:Retrospective Studies; D015996:Survival Rate
D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D016190:Carboplatin; D017239:Paclitaxel