Lauren C Harshman1, Wanling Xie2, Raphael B Moreira1,3, Dominick Bossé1, Gustavo J Ruiz Ares1,4, Christopher J Sweeney1, Toni K Choueiri1. 1. Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. 2. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts. 3. Oncoclinic Group, Alemao Oswaldo Cruz Hospital, Sao Paulo, Brazil. 4. Department of Clinical Oncology, University Hospital 12 de Octubre, Madrid, Spain.
Abstract
BACKGROUND: Overall survival (OS) is a critical endpoint in adjuvant trials but requires long durations to events and significant patient resources. In the current study, the authors assessed whether disease-free survival (DFS) can be an early clinical surrogate for OS in the adjuvant setting for localized renal cell carcinoma (RCC). METHODS: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the authors performed a systematic literature review of PubMed and the American Society of Clinical Oncology, European Society for Medical Oncology, and ClinicalTrial.gov Web sites (1996-2016). Inclusion in the current study required randomized controlled trials (RCTs) of adjuvant systemic therapy for localized RCC after nephrectomy with ≥3 years of outcomes data. Data regarding hazard ratios (HRs) and 5-year event-free rates from Kaplan-Meier estimates were extracted. A trial-level meta-analysis correlated estimates of 5-year DFS and 5-year OS as well as treatment effects (HRs) on these endpoints, weighted by the number of DFS events. R-squared ≥ 0.7 was prespecified as being indicative of a strong correlation and the potential for surrogacy. RESULTS: Thirteen RCTs encompassing 6473 patients who were treated with a variety of systemic therapies met eligibility. Only a modest correlation was observed between 5-year DFS and 5-year OS rates (R-squared, 0.48; 95% confidence interval, 0.14-0.67) and between treatment effects as measured by DFS and OS HRs (R-squared, 0.44; 95% confidence interval, 0.00-0.69). CONCLUSIONS: Across RCTs of adjuvant systemic therapy for localized RCC, there was no strong correlation noted between 5-year DFS and 5-year OS rates or between treatment effects on these endpoints. These results highlight the need to identify alternative and more rapid clinical or biologic endpoints to hasten drug development and improve clinical outcomes. Cancer 2018;124:925-33.
BACKGROUND: Overall survival (OS) is a critical endpoint in adjuvant trials but requires long durations to events and significant patient resources. In the current study, the authors assessed whether disease-free survival (DFS) can be an early clinical surrogate for OS in the adjuvant setting for localized renal cell carcinoma (RCC). METHODS: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the authors performed a systematic literature review of PubMed and the American Society of Clinical Oncology, European Society for Medical Oncology, and ClinicalTrial.gov Web sites (1996-2016). Inclusion in the current study required randomized controlled trials (RCTs) of adjuvant systemic therapy for localized RCC after nephrectomy with ≥3 years of outcomes data. Data regarding hazard ratios (HRs) and 5-year event-free rates from Kaplan-Meier estimates were extracted. A trial-level meta-analysis correlated estimates of 5-year DFS and 5-year OS as well as treatment effects (HRs) on these endpoints, weighted by the number of DFS events. R-squared ≥ 0.7 was prespecified as being indicative of a strong correlation and the potential for surrogacy. RESULTS: Thirteen RCTs encompassing 6473 patients who were treated with a variety of systemic therapies met eligibility. Only a modest correlation was observed between 5-year DFS and 5-year OS rates (R-squared, 0.48; 95% confidence interval, 0.14-0.67) and between treatment effects as measured by DFS and OS HRs (R-squared, 0.44; 95% confidence interval, 0.00-0.69). CONCLUSIONS: Across RCTs of adjuvant systemic therapy for localized RCC, there was no strong correlation noted between 5-year DFS and 5-year OS rates or between treatment effects on these endpoints. These results highlight the need to identify alternative and more rapid clinical or biologic endpoints to hasten drug development and improve clinical outcomes. Cancer 2018;124:925-33.
Authors: Maxine Sun; Lorenzo Marconi; Tim Eisen; Bernard Escudier; Rachel H Giles; Naomi B Haas; Lauren C Harshman; David I Quinn; James Larkin; Sumanta K Pal; Thomas Powles; Christopher W Ryan; Cora N Sternberg; Robert Uzzo; Toni K Choueiri; Axel Bex Journal: Eur Urol Date: 2018-05-18 Impact factor: 20.096
Authors: Giuseppe Fallara; Alessandro Larcher; Giuseppe Rosiello; Daniele Raggi; Laura Marandino; Alberto Martini; Giuseppe Basile; Gianmarco Colandrea; Daniele Cignoli; Federico Belladelli; Chiara Re; Giacomo Musso; Francesco Cei; Roberto Bertini; Alberto Briganti; Andrea Salonia; Francesco Montorsi; Andrea Necchi; Umberto Capitanio Journal: World J Urol Date: 2022-09-20 Impact factor: 3.661
Authors: Hiten D Patel; Maneka Puligandla; Brian M Shuch; Bradley C Leibovich; Anil Kapoor; Viraj A Master; Charles G Drake; Daniel Yc Heng; Primo N Lara; Toni K Choueiri; Deborah Maskens; Eric A Singer; Scott E Eggener; Robert S Svatek; Walter M Stadler; Suzanne Cole; Sabina Signoretti; Rajan T Gupta; Marc Dror Michaelson; David F McDermott; David Cella; Lynne I Wagner; Naomi B Haas; Michael A Carducci; Lauren C Harshman; Mohamad E Allaf Journal: Future Oncol Date: 2019-04-10 Impact factor: 3.404
Authors: Florence T H Wu; Ping Xu; Annabelle Chow; Shan Man; Janna Krüger; Kabir A Khan; Marta Paez-Ribes; Elizabeth Pham; Robert S Kerbel Journal: Br J Cancer Date: 2018-11-30 Impact factor: 7.640
Authors: Brian W Labadie; Ping Liu; Riyue Bao; Michael Crist; Ricardo Fernandes; Laura Ferreira; Scott Graupner; Andrew S Poklepovic; Ignacio Duran; Saman Maleki Vareki; Arjun V Balar; Jason J Luke Journal: J Transl Med Date: 2019-11-25 Impact factor: 5.531
Authors: L C Harshman; C G Drake; N B Haas; J Manola; M Puligandla; S Signoretti; D Cella; R T Gupta; R Bhatt; E Van Allen; P Lara; T K Choueiri; A Kapoor; D Y C Heng; B Shuch; M Jewett; D George; D Michaelson; M A Carducci; D McDermott; M Allaf Journal: Kidney Cancer Date: 2017-07-26