Randomized, Double-Blind, Phase II Study of Temozolomide in Combination With Either Veliparib or Placebo in Patients With Relapsed-Sensitive or Refractory Small-Cell Lung Cancer.
M. Catherine Pietanza,Saiama N. Waqar,Lee M. Krug,Afshin Dowlati,Christine L. Hann,Alberto Chiappori,Taofeek K. Owonikoko,Kaitlin M. Woo,Robert J. Cardnell,Junya Fujimoto,Lihong Long,Lixia Diao,Jing Wang,Yevgeniva Bensman,Brenda Hurtado,Patricia M. de Groot,Erik P. Sulman,Ignacio I. Wistuba,Alice P. Chen,Martin Fleisher,John V. Heymach,Mark G. Kris,Charles M. Rudin,Lauren Averett Byers +23 more
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TLDR
SLFN11 expression was associated with improved PFS and OS in patients receiving TMZ/veliparib, suggesting a promising biomarker of PARP-inhibitor sensitivity in SCLC.Abstract:
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.read more
Citations
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Canadian Consensus Recommendations on the Management of Extensive-Stage Small-Cell Lung Cancer
Barbara Melosky,Natasha B. Leighl,David E. Dawe,Normand Blais,Paul Wheatley-Price,Quincy Chu,Rosalyn A. Juergens,Peter M. Elias,Alexander Sun,Devin Schellenberg,Diana N. Ionescu,Parneet Cheema +11 more
TL;DR: A recent Canadian Expert Panel on Small Cell Lung Cancer (SCLC) as discussed by the authors reviewed evidence, discussed practice patterns, and reached a consensus on the treatment of extensive-stage SCLC.
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Kleinzelliges Lungenkarzinom – Etablierte Standards und neue Ansätze
Jan Weber,Martin Wermke +1 more
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Current and Emerging Treatment Options for Patients With Relapsed Small-cell Lung Carcinoma: A Systematic Literature Review.
TL;DR: In this article , the authors conducted a systematic literature review to evaluate the treatment landscape for patients with relapsed SCLC (PROSPERO number: CRD42022299759).
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Poly(Adenosine Diphosphate-Ribose) Polymerase Inhibition as Maintenance Treatment for SCLC: The Search Must Continue
Prerana Huddar,Raffaele Califano +1 more
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Therapeutic modalities in small cell lung cancer: a paradigm shift after decades of quiescence
Rola El Sayed,Haidar El Darsa +1 more
TL;DR: This review examines the main trials of SCLC treatment using chemotherapy, immunotherapy, and targeted treatment in the frontline or subsequent line settings, and concludes that no solid proof of efficacy has been established.
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Joaquin Mateo,Suzanne Carreira,Shahneen Sandhu,Susana Miranda,Helen Mossop,Raquel Perez-Lopez,Daniel Nava Rodrigues,Dan R. Robinson,Aurelius Omlin,Nina Tunariu,Gunther Boysen,Nuria Porta,Penny Flohr,Alexa Gillman,Ines Figueiredo,Claire Paulding,George Seed,Suneil Jain,Christy Ralph,Andrew Protheroe,Syed A. Hussain,Robert Jones,Tony Elliott,Ursula McGovern,Diletta Bianchini,Jane C. Goodall,Zafeiris Zafeiriou,Chris T. Williamson,Roberta Ferraldeschi,Ruth Riisnaes,Bernardette Ebbs,Gemma Fowler,Desamparados Roda,Wei Yuan,Yi-Mi Wu,Xuhong Cao,Rachel Brough,Helen Pemberton,Roger A'Hern,Amanda Swain,Lakshmi P. Kunju,Rosalind A. Eeles,Gerhardt Attard,Christopher J. Lord,Alan Ashworth,Mark A. Rubin,Karen E. Knudsen,Felix Y. Feng,Arul M. Chinnaiyan,Emma Hall,Johann S. de Bono +50 more
TL;DR: Treatment with the PARP inhibitor olaparib in patients whose prostate cancers were no longer responding to standard treatments and who had defects in DNA-repair genes led to a high response rate.
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