title: Randomized phase IIIb trial evaluating the continuation of bevacizumab beyond disease progression in patients with advanced non-squamous non-small-cell lung cancer after first-line treatment with bevacizumab plus platinum-based chemotherapy: treatment rationale and protocol dynamics of the AvaALL (MO22097) trial.
abstract: We present the treatment rationale and study design of the AvaALL (MO22097; ClinicalTrials: NCT01351415) trial, a multicenter, open-label, randomized, two-arm, phase IIIb study. Patients with advanced non-squamous non-small-cell lung cancer (NSCLC) whose disease has progressed after four to six cycles of first-line treatment with bevacizumab plus a platinum-based doublet and a minimum of two cycles of bevacizumab (monotherapy) maintenance treatment will be randomized in a 1:1 ratio to one of two study arms. Patients treated on arm A will receive bevacizumab 7.5 or 15 mg/kg intravenously (I.V.) on day 1, every 21 days plus, investigator's choice of agents indicated for use in second-line (limited to pemetrexed, docetaxel, or erlotinib) and subsequent lines of treatment. Patients treated on arm B, will receive investigator's choice of agents alone indicated for use in second-line and subsequent lines of treatment, but no further bevacizumab treatment. The primary endpoint of this study is overall survival (OS). Secondary endpoints include the 6-month, 12-month, and 18-month OS rates, progression-free survival, and time to progression at second and third progressive disease (PD), response rate, disease control rates, and duration of response at second and third PD. Additionally, efficacy in the subgroup of patients with adenocarcinoma, and the safety of bevacizumab treatment across multiple lines of treatment will be assessed. Exploratory objectives include assessment of the quality of life through multiple lines of treatment, comparison of the efficacy between Asian and non-Asian patients, and correlation of biomarkers with efficacy outcomes, disease response, and adverse events.
authors.affiliation: Division of Medical Oncology, SG Moscati Hospital, Avellino, Italy. cgridelli@libero.it
authors.forename: Cesare
authors.initials: C
authors.lastname: Gridelli
authors.forename: Jaafar
authors.initials: J
authors.lastname: Bennouna
authors.forename: Javier
authors.initials: J
authors.lastname: de Castro
authors.forename: Anne-Marie C
authors.initials: AM
authors.lastname: Dingemans
authors.forename: Frank
authors.initials: F
authors.lastname: Griesinger
authors.forename: Francesco
authors.initials: F
authors.lastname: Grossi
authors.forename: Antonio
authors.initials: A
authors.lastname: Rossi
authors.forename: Nick
authors.initials: N
authors.lastname: Thatcher
authors.forename: Elaine K
authors.initials: EK
authors.lastname: Wong
authors.forename: Corey
authors.initials: C
authors.lastname: Langer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000077143:Docetaxel; D000069347:Erlotinib Hydrochloride; D005260:Female; D005500:Follow-Up Studies; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D007390:International Agencies; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D000068437:Pemetrexed; D010984:Platinum / Q000008:administration & dosage; D011788:Quality of Life; D011799:Quinazolines / Q000008:administration & dosage; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D005971:Glutamates; D011799:Quinazolines; D043823:Taxoids; D000068437:Pemetrexed; D000077143:Docetaxel; D000068258:Bevacizumab; D010984:Platinum; D006147:Guanine; D000069347:Erlotinib Hydrochloride