Progression-free survival and overall survival in phase III trials of molecular-targeted agents in advanced non-small-cell lung cancer

Hotta, Katsuyuki; Suzuki, Etsuji; Maïo, Massimo Di; Chiodini, Paolo; Fujiwara, Yoshiro; Takigawa, Nagio; Ichihara, Eiki; Reck, Martin; Manegold, Christian; Pilz, Lothar R.; Hisamoto-Sato, Akiko; Tabata, Masahiro; Tanimoto, Mitsune; Shepherd, Frances A.; Kiura, Katsuyuki

doi:10.1016/j.lungcan.2012.10.007

Cited by 37 publications

(30 citation statements)

References 31 publications

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“…Accordingly, the extent to which a 25% reduction in all-cause mortality represents an achievable outcome in IPF clinical trials is uncertain. However, as noted previously, relevant benchmarks in lung cancer and cardiovascular disease suggest that our assumption regarding the magnitude of treatment effect was comparatively large and therefore provided a conservatively small estimate of sample size (15)(16)(17)(18)(19)(20).…”

Section: Figurementioning

confidence: 80%

All-Cause Mortality Rate in Patients with Idiopathic Pulmonary Fibrosis. Implications for the Design and Execution of Clinical Trials

King

Albera

Bradford³

et al. 2014

Am J Respir Crit Care Med

147

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All-cause mortality rate in patients with idiopathic pulmonary fibrosis. Implications for the design and execution of clinical trials.King TE Jr 1 , Albera C, Bradford WZ, Costabel U, du Bois RM, Leff JA, Nathan SD, Sahn SA, Valeyre D, Noble PW. La versione definitiva è disponibile alla URL:http: //www.atsjournals.org/doi/abs/10.1164 Rationale: FVC has emerged as a standard primary endpoint in clinical trials evaluating novel therapies for patients with idiopathic pulmonary fibrosis (IPF). However, it has recently been proposed that all-cause mortality or a composite comprised of all-cause mortality and all-cause nonelective hospitalization be adopted as the standard primary endpoint for IPF clinical trials.Objectives: To conduct a comprehensive evaluation of mortality in three phase 3 clinical trials and evaluate the feasibility of mortality trials in patients with IPF. Methods:The study population included 622 patients randomized to placebo in the CAPACITY studies evaluating pirfenidone (n = 347) or the INSPIRE study evaluating interferon-γ1b (n = 275). The Kaplan-Meier estimate of 2-year survival was fit to the exponential distribution and used to calculate sample size requirements for a mortality study with 90% power to detect a 25% reduction in all-cause mortality with a two-sided α of 0.05. Modeling analyses were used to assess the effects of selected variables on sample size and study design. Measurements and Main Results:A total of 73 deaths occurred during the period of observation (mean duration of follow-up, 80.1 wk). The all-cause mortality rate was 6.6% at 1 year and 13.7% at 2 years. Based on the observed 2-year mortality rate, a total of 508 events would be required to detect a significant treatment benefit in a two-arm trial with 90% power to detect a 25% reduction in all-cause mortality. The estimated sample size for a trial enrolled over 3 years with a maximum follow-up period of 5 years is 2,582 patients. Conclusions:The all-cause mortality rate is relatively low in patients with IPF with mild to moderate impairment in lung function. Accordingly, the necessary size, duration, and cost of allcause mortality trials in this population are substantial and likely prohibitive.

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Section: Figurementioning

confidence: 80%

All-Cause Mortality Rate in Patients with Idiopathic Pulmonary Fibrosis. Implications for the Design and Execution of Clinical Trials

King

Albera

Bradford³

et al. 2014

Am J Respir Crit Care Med

147

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“…Among the six, some articles considered both published and unpublished clinical trials (15,30,40); the others analysed the extent to which bias represents a problem using Egger's regression test (13,24,41).…”

Section: ) Lack Of Rigour In Applying Methodologymentioning

confidence: 99%

“…Crossover (13,23,30,33,41) Some clinical trials allow crossover to the experimental regimen upon disease progression. This hinders the analysis of the treatment effect on OS.…”

Section: )mentioning

confidence: 99%

“…In melanoma, Flaherty, Hennig (23) suggested that correlation coefficients for the nine trials without crossover were significant and more than 7 percentage points higher than with crossover. Hotta, Suzuki (30), in studying NSCLC, suggest that for clinical trials in which the median proportion of crossover was lower than 1%, the association between the HRs of PFS and OS was strong. Kim and Prasad (56), identified by Davis, Tappenden (1), evaluated previous publications to assess the strength of the surrogate-survival correlation among cancer drugs approved.…”

Section: )mentioning

confidence: 99%

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Challenges and Methodologies in Using Progression Free Survival as a Surrogate for Overall Survival in Oncology

Hernández-Villafuerte¹,

Fischer

Latimer

2018

Int J Technol Assess Health Care

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Objectives: A primary outcome in oncology trials is overall survival (OS). However, to estimate OS accurately requires a sufficient number of patients to have died, which may take a long time. If an alternative endpoint is sufficiently highly correlated with OS, it can be used as a surrogate. Progression-free survival (PFS) is the surrogate most often used in oncology, but does not always satisfy the correlation conditions for surrogacy.We analyse the methodologies used when extrapolating from PFS to OS. Methods: A wide range of methods has been used to determine the appropriateness of surrogates.While usually adhering to reporting standards, the standard of scholarship appears sometimes to be questionable and the reporting of results often haphazard. Conclusion:Standards of analysis and reporting PFS to OS surrogate studies should be improved by increasing the rigour of statistical reporting and by agreeing to a minimum set of reporting guidelines. Moreover, the use of IPD to assess surrogacy should increase.

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“…In that study, an interim analysis of overall survival showed no significant improvement with crizotinib as compared with chemotherapy (hazard ratio for death in the crizotinib group, 1.02; 95% CI, 0.68-1.54; p=0.54). However, as a general rule, when a significant proportion of patients assigned to the control arm receives the experimental drug as crossover after disease progression, this is expected to dilute the differences in terms of overall survival between the two arms (15). This is what has been systematically observed in the trials of first-line epidermal growth factor receptor (EGFR) inhibitors vs. chemotherapy in EGFR mutated cases (16).…”

Section: Which Line Of Treatment For Crizotinib?mentioning

confidence: 99%

Diagnostic and therapeutic issues for patients with advanced non-small cell lung cancer harboring anaplastic lymphoma kinase rearrangement: European vs. US perspective (Review)

Maïo

Marinis

Hirsch

et al. 2014

International Journal of Oncology

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The recent availability of crizotinib in clinical practice, for the treatment of patients with advanced non-small cell lung cancer (NSCLC) selected by the presence of anaplastic lymphoma kinase (ALK) rearrangement, has relevant implications for both the diagnostic phase and the treatment choices. In the United States, crizotinib was approved by the Food and Drug Administration (FDA) in 2011 for patients with ALK positivity detected by FDA-approved companion diagnostic test. As of January, 2014, the only FDA-approved diagnostic test is Vysis ALK Break-Apart FISH Probe Kit. In Europe, European Medicines Agency (EMA) approved crizotinib for ALK-positive patients in 2012, without specifying the type of test used for determining the positivity. FISH remains the reference technique for ALK determination, but, if fully validated, immunohistochemistry could challenge the current ALK screening practice. Given the robust evidence of activity of crizotinib in ALK-positive patients both pretreated and chemotherapy-naïve, and the favourable tolerability profile of the drug, many oncologists would prefer to administer the drug as early as possible. This is technically feasible in the United States, where crizotinib was approved well before the availability of the results of the randomized phase III trial comparing the drug with standard second-line chemotherapy, and the use of crizotinib in ALK-positive patients is not restricted to a specific line of treatment. On the contrary, in Europe, differently from the FDA decision, crizotinib cannot be used in chemotherapy-naïve patients. In both realities, a deeper knowledge of mechanisms of resistance, the role of repeated biopsies, the treatment strategy for patients experiencing disease progression with crizotinib, the choice of the best chemotherapy regimen are challenging topics for the management of ALK-positive patients in clinical practice.

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Progression-free survival and overall survival in phase III trials of molecular-targeted agents in advanced non-small-cell lung cancer

Cited by 37 publications

References 31 publications

All-Cause Mortality Rate in Patients with Idiopathic Pulmonary Fibrosis. Implications for the Design and Execution of Clinical Trials

All-Cause Mortality Rate in Patients with Idiopathic Pulmonary Fibrosis. Implications for the Design and Execution of Clinical Trials

Challenges and Methodologies in Using Progression Free Survival as a Surrogate for Overall Survival in Oncology

Diagnostic and therapeutic issues for patients with advanced non-small cell lung cancer harboring anaplastic lymphoma kinase rearrangement: European vs. US perspective (Review)

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