Search

Introduction: There is no predictive factor of response to bevacizumab in metastatic colorectal cancer. Nevertheless, preclinical studies demonstrated an interaction between primary tumor and metastatic sites for the neoangiogenesis regulation. The primary objective of our study was to identify an effect of up-front primary tumor resection (UPTR) on bevacizumab efficacy., Patients and Methods: Between 2008 and 2010, we retrospectively analyzed progression-free survival (PFS) and overall survival (OS) of 316 patients with synchronous and metachronous metastatic colorectal cancer according to bevacizumab addition to first-line chemotherapy and UPTR., Results: Among 206 patients with UPTR, the addition of bevacizumab to chemotherapy significantly improved OS compared to chemotherapy alone (29.8 vs. 23.9 months respectively; hazard ratio [HR] 0.58; 95% confidence interval [CI], 0.40-0.83; P = .003). This effect was confirmed in multivariate analysis. There was also a nonsignificant trend toward improved PFS (9.7 vs. 8.4 months respectively; HR 0.71; 95% CI, 0.50-1.02; P = .062). Conversely, among 110 patients without UPTR, the addition of bevacizumab to chemotherapy had no effect on OS compared to chemotherapy alone (18.2 vs. 19.3 months respectively; HR 0.96; 95% CI, 0.65-1.42; P = .853). Bevacizumab significantly improved PFS (8.1 vs. 5.7 months respectively; HR 0.66; 95% CI, 0.45-0.96; P = .032) without confirmation in multivariate analysis., Conclusion: In this retrospective study, bevacizumab seems to improve OS only in patients with UPTR, which could suggest a complementarity of both therapeutic modalities for antiangiogenic effect., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: The identification of RAS status (KRAS and NRAS) has changed the management of metastatic colorectal cancer (mCRC). The impact of the RAS mutation on cytotoxic chemotherapy efficacy has not yet been determined. Nevertheless, several retrospective studies suggest a greater efficacy of oxaliplatin in mCRC with KRAS mutation., Methods: We analyzed retrospectively the progression free survival (PFS) and overall survival (OS) in 216 patients with mCRC receiving first line treatment between 2008 and 2010 according to KRAS status and chemotherapy regimen used (oxaliplatin- or irinotecan-based, in association with fluoropyrimidine and bevacizumab)., Results: In KRAS mutated tumors, median OS was 23.4 months with oxaliplatin-based regimen, and 23.6 months with irinotecan-based regimen, with no significant difference (HR 1.30; 95 % CI 0.81-2.09; P=0.27). In KRAS wild-type tumors, median OS was 30.3 months with oxaliplatin-based regimen, and 25.4 months with irinotecan-based regimen, with no significant difference (HR 0.81; 95 % CI 0.52-1.24; P=0.33). Similarly, KRAS mutational status had no significant effect on efficacy of oxaliplatin or irinotecan regarding PFS., Discussion: In this retrospective study, KRAS mutational status does not influence the efficacy of first line cytotoxic chemotherapy in association with bevacizumab., (Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Purpose: The phase II prospective, noncomparative BRAIN study (NCT00800202) investigated efficacy and safety of bevacizumab in chemotherapy-naïve or pretreated patients with non-small cell lung cancer (NSCLC) and asymptomatic untreated brain metastases to provide data in this previously unexplored subgroup., Experimental Design: Patients with stage IV nonsquamous NSCLC, Eastern Cooperative Oncology Group performance status 0-1, and untreated, asymptomatic brain metastases received first-line bevacizumab (15 mg/kg) plus carboplatin (area under the curve ×6) and paclitaxel (200 mg/m(2)) every 3 weeks (B + CP), or second-line bevacizumab plus erlotinib (150 mg/d; B + E). Six-month progression-free survival (PFS) was the primary endpoint. The trial could be stopped if there were more than three (B + CP) or more than two (B + E) intracranial hemorrhages., Results: In first-line B + CP cohort (n = 67), 6-month PFS rate was 56.5% with a median PFS of 6.7 months [95% confidence interval (CI), 5.7-7.1] and median overall survival (OS) of 16.0 months. Investigator-assessed overall response rate (ORR) was 62.7%: 61.2% in intracranial lesions and 64.2% in extracranial lesions. Because of low enrolment (n = 24), efficacy results for the second-line B + E cohort were exploratory only; 6-month PFS rate was 57.2%, median PFS was 6.3 months (95% CI, 3.0-8.4), median OS was 12.0 months, and ORR was 12.5%. Adverse events were comparable with previous trials of bevacizumab. One grade 1 intracranial hemorrhage occurred and resolved without sequelae., Conclusions: The BRAIN study demonstrates encouraging efficacy and acceptable safety of bevacizumab with first-line paclitaxel and carboplatin in patients with NSCLC and asymptomatic, untreated brain metastases., (©2015 American Association for Cancer Research.)