Induction pemetrexed and cisplatin followed by maintenance pemetrexed versus carboplatin plus paclitaxel plus bevacizumab followed by maintenance bevacizumab: a quality of life-oriented randomized phase III study in patients with advanced non-squamous non

In advanced non-small-cell lung cancer (NSCLC), substantial similarities in terms of treatment efficacy and survival have emerged over the years between the different systemic chemotherapy regimens used. More recently, other topics such as histotype, maintenance therapy and quality of life have been explored to ameliorate this plateau. We present the treatment rationale and study design of the ERACLE (induction pEmetrexed and cisplatin followed by maintenance pemetRexed versus cArboplatin-paCLitaxel and bEvacizumab followed by maintenance bevacizumab) trial. Patients enrolled in the ERACLE trial are randomized between combination treatment arms: (A) cisplatin 75 mg/m(2) day 1 and pemetrexed 500 mg/m(2) day 1, every 3 weeks for six cycles followed (in responders or with stable disease) by pemetrexed 500 mg/m(2) day 1, every 3 weeks until progression; and (B) carboplatin AUC 6 day 1, plus paclitaxel 200 mg/m(2) day 1 and plus bevacizumab 15 mg/kg, every 3 weeks for six cycles followed (in responders or patients with stable disease) by bevacizumab 15 mg/kg every 3 weeks until progression. The primary objective of the study is to evaluate the difference in terms of quality of life between treatment arms. together with co-primary endpoints represented by the EuroQoL group (EQ-5D) questionnaire total score and the EQ-5D visual analog scale. Secondary endpoints are the evaluation of treatment activity and exploratory evaluation of treatment efficacy.

Galetta D ，Pisconti S ，Cinieri S ，Pappagallo GL ，Gebbia V ，Borsellino N ，Maiello E ，Rinaldi A ，Montrone M ，Rizzo P ，Marzano N ，Sasso N ，Febbraro A ，Colucci G ... -  《-》

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 rat

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.

Gridelli C ，Bennouna J ，de Castro J ，Dingemans AM ，Griesinger F ，Grossi F ，Rossi A ，Thatcher N ，Wong EK ，Langer C ... -  《-》

Treatment rationale and study design for the pointbreak study: a randomized, open-label phase III study of pemetrexed/carboplatin/bevacizumab followed by maintenance pemetrexed/bevacizumab versus paclitaxel/carboplatin/bevacizumab followed by maintenance

Patel JD ，Bonomi P ，Socinski MA ，Govindan R ，Hong S ，Obasaju C ，Pennella EJ ，Girvan AC ，Guba SC ... -  《-》

Cisplatin/Pemetrexed Followed by Maintenance Pemetrexed Versus Carboplatin/Paclitaxel/Bevacizumab Followed by Maintenance Bevacizumab in Advanced Nonsquamous Lung Cancer: The GOIM (Gruppo Oncologico Italia Meridionale) ERACLE Phase III Randomized Trial.

Cisplatin with pemetrexed (CP) and carboplatin with paclitaxel and bevacizumab (CbTB) are standard first-line treatments for patients with advanced nonsquamous (NS) non-small-cell lung cancer (NSCLC). Quality of life (QoL) is a key objective in the management of advanced NSCLC. Thus, effect on QoL could be an additional factor in the choice of treatment. Patients with untreated stage IIIB/IV NS-NSCLC and Eastern Cooperative Oncology Group performance status of 0 or 1 were randomized to receive first-line chemotherapy with cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2), every 3 weeks, for 6 cycles followed by maintenance pemetrexed; or carboplatin area under the curve 6, paclitaxel 200 mg/m(2), and bevacizumab 15 mg/kg, every 3 weeks, for 6 cycles followed by maintenance bevacizumab. The primary end point was the difference in QoL between the 2 treatment arms after 12 weeks of maintenance, measured using the EuroQoL 5 Dimensions-Index (EQ5D-I) and EQ5D-visual analogue scale (EQ5D-VAS). One hundred eighteen patients were randomized to CP (n = 60) or CbTB (n = 58). Baseline characteristics were well balanced. The proportion of patients evaluable for the primary end point was lower than planned. After 12 weeks of maintenance, the difference between mean changes in EQ5D-I was 0.137, favoring CP (95% confidence interval [CI], -0.02 to 0.29, Wilcoxon P = .078), although not statistically significant; and the difference between mean changes in EQ5D-VAS was 0.97 (95% CI, -9.37 to 11.31, Wilcoxon P = .41). Although the study was underpowered because of a small number of patients evaluable for the primary end point, QoL did not differ between treatment arms. Other factors such as comorbidities and schedule should be used when deciding on first-line treatment.

Galetta D ，Cinieri S ，Pisconti S ，Gebbia V ，Morabito A ，Borsellino N ，Maiello E ，Febbraro A ，Catino A ，Rizzo P ，Montrone M ，Misino A ，Logroscino A ，Rizzi D ，Di Maio M ，Colucci G ... -  《-》

Treatment rationale and study design for a randomized trial of pemetrexed/carboplatin followed by maintenance pemetrexed versus paclitaxel/carboplatin/bevacizumab followed by maintenance bevacizumab in patients with advanced non-small-cell lung cancer of

Zinner RG ，Saxman SB ，Peng G ，Monberg MJ ，Ortuzar WI ... -  《-》