1359TiP RELATIVITY-104: First-line relatlimab (RELA) + nivolumab (NIVO) with chemotherapy vs nivo with chemotherapy in stage IV or recurrent non-small cell lung cancer (NSCLC): A phase II, randomized, double-blind study

Purpose Both temozolomide (TMZ) and poly (ADP-ribose) polymerase (PARP) inhibitors are active in small-cell lung cancer (SCLC). This phase II, randomized, double-blind study evaluated whether addition of the PARP inhibitor veliparib to TMZ improves 4-month progression-free survival (PFS). Patients and Methods A total of 104 patients with recurrent SCLC were randomly assigned 1:1 to oral veliparib or placebo 40 mg twice daily, days 1 to 7, and oral TMZ 150 to 200 mg/m2/day, days 1 to 5, of a 28-day cycle until disease progression, unacceptable toxicity, or withdrawal of consent. Response was determined by imaging at weeks 4 and 8, and every 8 weeks thereafter. Improvement in PFS at 4 months was the primary end point. Secondary objectives included overall response rate (ORR), overall survival (OS), and safety and tolerability of veliparib with TMZ. Exploratory objectives included PARP-1 and SLFN11 immunohistochemical expression, MGMT promoter methylation, and circulating tumor cell quantification. Results No significant difference in 4-month PFS was noted between TMZ/veliparib (36%) and TMZ/placebo (27%; P = .19); median OS was also not improved significantly with TMZ/veliparib (8.2 months; 95% CI, 6.4 to 12.2 months; v 7.0 months; 95% CI, 5.3 to 9.5 months; P = .50). However, ORR was significantly higher in patients receiving TMZ/veliparib compared with TMZ/placebo (39% v 14%; P = .016). Grade 3/4 thrombocytopenia and neutropenia more commonly occurred with TMZ/veliparib: 50% versus 9% and 31% versus 7%, respectively. Significantly prolonged PFS (5.7 v 3.6 months; P = .009) and OS (12.2 v 7.5 months; P = .014) were observed in patients with SLFN11-positive tumors treated with TMZ/veliparib. Conclusion Four-month PFS and median OS did not differ between the two arms, whereas a significant improvement in ORR was observed with TMZ/veliparib. SLFN11 expression was associated with improved PFS and OS in patients receiving TMZ/veliparib, suggesting a promising biomarker of PARP-inhibitor sensitivity in SCLC.

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PF-06439535 (a Bevacizumab Biosimilar) Compared with Reference Bevacizumab (Avastin®), Both Plus Paclitaxel and Carboplatin, as First-Line Treatment for Advanced Non-Squamous Non-Small-Cell Lung Cancer: A Randomized, Double-Blind Study

BioDrugs ◽

10.1007/s40259-019-00363-4 ◽

2019 ◽

Vol 33 (5) ◽

pp. 555-570 ◽

Cited By ~ 7

Author(s):

Niels Reinmuth ◽

Maciej Bryl ◽

Igor Bondarenko ◽

Kostas Syrigos ◽

Vladimir Vladimirov ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Double Blind Study ◽

Line Treatment ◽

Small Cell Lung ◽

First Line ◽

Double Blind ◽

First Line Treatment

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ATLAS: Randomized, Double-Blind, Placebo-Controlled, Phase IIIB Trial Comparing Bevacizumab Therapy With or Without Erlotinib, After Completion of Chemotherapy, With Bevacizumab for First-Line Treatment of Advanced Non–Small-Cell Lung Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2012.47.3983 ◽

2013 ◽

Vol 31 (31) ◽

pp. 3926-3934 ◽

Cited By ~ 110

Author(s):

Bruce E. Johnson ◽

Fairooz Kabbinavar ◽

Louis Fehrenbacher ◽

John Hainsworth ◽

Saifuddin Kasubhai ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Stage Iv ◽

Small Cell ◽

Phase Iii ◽

Random Assignment ◽

Small Cell Lung ◽

First Line ◽

Double Blind

Purpose This phase III trial was performed to assess the potential benefit of adding maintenance erlotinib to bevacizumab after a first-line chemotherapy regimen with bevacizumab for advanced non–small-cell lung cancer (NSCLC). Patients and Methods One thousand one hundred forty-five patients with histologically or cytologically confirmed NSCLC (stage IIIB with malignant pleural effusion, stage IV, or recurrent) received four cycles of chemotherapy plus bevacizumab. Seven hundred forty-three patients without disease progression or significant toxicity were then randomly assigned (1:1) to bevacizumab (15 mg/kg, day 1, 21-day cycle) plus either placebo or erlotinib (150 mg per day). The primary end point was progression-free survival (PFS). Results Median PFS from time of random assignment was 3.7 months with bevacizumab/placebo and 4.8 months with bevacizumab/erlotinib (hazard ratio [HR], 0.71; 95% CI, 0.58 to 0.86; P < .001). Median overall survival (OS) times from random assignment were 13.3 and 14.4 months with bevacizumab/placebo and bevacizumab/erlotinib, respectively (HR, 0.92; 95% CI, 0.70 to 1.21; P = .5341). During the postchemotherapy phase, there were more adverse events (AEs) overall, more grade 3 and 4 AEs (mainly rash and diarrhea), more serious AEs, and more AEs leading to erlotinib/placebo discontinuation in the bevacizumab/erlotinib arm versus the bevacizumab/placebo arm. The incidence of AEs leading to bevacizumab discontinuation was similar in both treatment arms. Conclusion The addition of erlotinib to bevacizumab significantly improved PFS but not OS. Although generally well tolerated, the modest impact on survival and increased toxicity associated with the addition of erlotinib to bevacizumab maintenance mean that this two-drug maintenance regimen will not lead to a new postchemotherapy standard of care.

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