TY - JOUR
TI - Safety and Efficacy of Bevacizumab Plus Standard-of-Care Treatment Beyond Disease Progression in Patients With Advanced Non-Small Cell Lung Cancer: The AvaALL Randomized Clinical Trial
AU - Gridelli, C.
AU - De Castro Carpeno, J.
AU - Dingemans, A.-M.C.
AU - Griesinger, F.
AU - Grossi, F.
AU - Langer, C.
AU - Ohe, Y.
AU - Syrigos, K.
AU - Thatcher, N.
AU - Das-Gupta, A.
AU - Truman, M.
AU - Donica, M.
AU - Smoljanovic, V.
AU - Bennouna, J.
JO - JAMA Oncology
PY - 2018
VL - 4
TODO - 12
SP - null
PB - American Medical Association
SN - 2374-2437, 2374-2445
TODO - 10.1001/jamaoncol.2018.3486
TODO - antineoplastic agent;  bevacizumab;  platinum complex;  antineoplastic agent;  bevacizumab, adult;  advanced cancer;  aged;  Article;  cancer survival;  controlled study;  deep vein thrombosis;  disease course;  disease severity;  drug efficacy;  drug safety;  drug withdrawal;  female;  human;  hypertension;  kidney disease;  lung embolism;  major clinical study;  male;  middle aged;  multiple cycle treatment;  non small cell lung cancer;  open study;  overall survival;  phase 3 clinical trial;  progression free survival;  proteinuria;  randomized controlled trial;  treatment outcome;  urinary tract disease;  vascular disease;  vein thrombosis;  very elderly;  adverse event;  clinical trial;  disease exacerbation;  disease free survival;  health care quality;  lung tumor;  mortality;  multicenter study;  multimodality cancer therapy;  non small cell lung cancer;  pathology;  survival analysis, Adult;  Aged;  Aged, 80 and over;  Antineoplastic Combined Chemotherapy Protocols;  Bevacizumab;  Carcinoma, Non-Small-Cell Lung;  Combined Modality Therapy;  Disease Progression;  Disease-Free Survival;  Female;  Humans;  Lung Neoplasms;  Male;  Middle Aged;  Standard of Care;  Survival Analysis;  Treatment Outcome
TODO - Importance: Bevacizumab treatment beyond progression has been investigated in breast and metastatic colorectal cancers. Avastin in All Lines Lung (AvaALL) is the first randomized phase 3 study of bevacizumab across multiple lines of treatment beyond progression in non-small cell lung cancer (NSCLC). Objective: To assess the efficacy and safety of continuous bevacizumab treatment beyond first progression in NSCLC. Design, Setting, and Participants: AvaALL was a randomized, open-label, phase 3b trial, conducted from 2011 to 2015 in 123 centers worldwide. Patients with nonsquamous NSCLC previously treated with first-line bevacizumab plus platinum-doublet chemotherapy and at least 2 cycles of bevacizumab maintenance were randomized (1:1) at first progression to receive bevacizumab plus standard of care (SOC) or SOC alone. Interventions: Patients received bevacizumab (7.5 or 15 mg/kg intravenously every 21 days) and/or investigator's choice of SOC. For subsequent lines, patients treated with bevacizumab received SOC with or without bevacizumab; the SOC arm received SOC only. Main Outcomes and Measures: The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival from first to second (PFS2) and third progression (PFS3), time to second (TTP2) and third progression (TTP3), and safety. Results: Between June 2011 and January 2015, 485 patients (median age, 63.0 years [range, 26-84 years]; 293 [60.4%] male) were randomized. Median OS was not significantly longer with bevacizumab plus SOC vs SOC alone: 11.9 (90% CI, 10.2-13.7) vs 10.2 (90% CI, 8.6-11.9) months (hazard ratio [HR], 0.84; 90% CI, 0.71-1.00; P =.104). Median PFS2 was numerically longer with bevacizumab plus SOC vs SOC alone: 5.5 (90% CI, 4.2-5.7) vs 4.0 (90% CI, 3.4-4.3) months (HR, 0.83; 90% CI, 0.70-0.98; P =.06). Median PFS3 appeared longer with bevacizumab plus SOC vs SOC alone: 4.0 (90% CI, 2.9-4.5) vs 2.6 (90% CI, 2.3-2.9) months (HR, 0.63; 90% CI, 0.49-0.83), as did TTP2 and TTP3. Grade 3/4 adverse events were more frequent with bevacizumab plus SOC (186 [76.5%]) vs SOC alone (140 [60.3%]). No new safety signals were observed. Conclusions and Relevance: The primary end point was not met; however, OS was underpowered according to initial statistical assumptions. Continued therapy beyond first progression led to improved PFS3 (but not PFS2), TTP2, and TTP3. Although a result with P =.06 for PFS2 would conventionally be considered significant at a specified 2-sided α of.10, in the absence of adjustments for multiplicity, this result could be a chance finding. No new safety signals were identified with bevacizumab treatment beyond progression. © 2018 American Medical Association. All rights reserved.
ER -