Abstract 2935
Background
Overall survival (OS) has become the definitive endpoint in oncology clinical trials, but may be difficult to assess due to need for lengthy follow-up, factors related to trial design or impacted by study crossover. Progression free survival (PFS) is a common primary endpoint, but, differential response to subsequent therapy may affect the correlation of PFS and OS. The European Medicines Agency encourages the use of PFS2, defined as time from initial study randomization to 2nd disease progression or death from any cause. The surrogacy of PFS2 for OS has not been confirmed. This analysis used published data from solid tumor clinical studies to assess whether PFS2 and OS are correlated.
Methods
A systematic literature search identified solid tumor oncology studies that included data for PFS, PFS2, and OS. Two independent reviewers screened titles, abstracts and main-text of study reports for eligibility, and collected data on median time to PFS2, PFS or time from 1st progression to 2nd disease progression or death, and median time to OS. The correlation between PFS2 and OS was assessed and verified in two steps: (1) Kendall’s Tau (Kendall rank correlation coefficient) statistics and Pearson’s correlation coefficient in randomized controlled trials (RCTs); (2) Meta-analysis with the random effects model to compute the pooled correlation of PFS2 and OS.
Results
In total, 133 studies met the search criteria and 15 trials had complete PFS2 and OS data (28 individual treatment and control arms) in ovarian, gastric, colorectal, prostate, lung, renal and breast tumors. A positive correlation was observed between PFS2 and OS (Kendall’s Tau = 0.7 (95% CIs 0.54, 0.78) using all 15 studies. Data from the 10 RCTs showed a Pearson’s correlation coefficient = 0.86. An additional meta-analysis of 3 tumors (breast, colorectal, and lung cancer), where more than 1 study per indication was available (7 studies; 17 individual arms), identified a Spearman’s correlation coefficient = 0.84 (p = 0.0001; 95% CIs 0.71, 0.96).
Conclusions
In this retrospective analysis in solid tumors, PFS2 was positively correlated with OS. The strong correlation provides confidence in using PFS2 as a surrogate for OS before OS data are mature or when OS cannot be assessed.
Clinical trial identification
Editorial acknowledgement
Editorial assistance was provided by Ann C Sherwood, PhD with funding from Janssen Pharmaceuticals.
Legal entity responsible for the study
Janssen Pharmaceuticals.
Funding
Janssen Pharmaceuticals.
Disclosure
P.N. Mainwaring: Leadership role, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Licensing / Royalties: XING Technologies P/L; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer. L. Zhang: Shareholder / Stockholder / Stock options, Full / Part-time employment: Janssen. S.D. Mundle: Shareholder / Stockholder / Stock options, Full / Part-time employment: Janssen. K. Liu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Janssen. E. Pollozi: Shareholder / Stockholder / Stock options, Full / Part-time employment: IDEA Pharma; Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer; Advisory / Consultancy: Janssen. A. Gray: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: IDEA Pharma; Advisory / Consultancy: Janssen. M. Wildgust: Shareholder / Stockholder / Stock options, Full / Part-time employment: Janssen.
Resources from the same session
1851 - Nivolumab-induced and radiation recall pneumonitis in patients with non-small cell lung cancer: a multicenter real world analysis of 669 patients
Presenter: Nobuaki Mamesaya
Session: Poster Display session 1
Resources:
Abstract
851 - Retrospective analysis of immunotherapy prognostic scores in advanced NSCLC at Nottingham University Hospitals (UK)
Presenter: Cristina Lopez Escola
Session: Poster Display session 1
Resources:
Abstract
3639 - Applicability of lung immune prognostic index (LIPI) to predict efficacy of first-line pembrolizumab in advanced non-small-cell lung cancer (NSCLC)
Presenter: Xabier Mielgo Rubio
Session: Poster Display session 1
Resources:
Abstract
2950 - Delayed Onset Immune Related Adverse Effects (IRAEs) of Pembrolizumab in Non-Small Cell Lung Cancer
Presenter: Haixi Yan
Session: Poster Display session 1
Resources:
Abstract
3659 - Clinical implication of multiplex IHC and serologic biomarkers on Hyperprogression in NSCLC patients receiving Immune checkpoint blockers in real world.
Presenter: Joori Kim
Session: Poster Display session 1
Resources:
Abstract
4882 - Local ablative treatment and treatment beyond progression for oligo-progression in stage IV non-small cell lung cancer after tumor response to anti-PD1 treatment
Presenter: Florian Guisier
Session: Poster Display session 1
Resources:
Abstract
1358 - Atezolizumab in combination with chemotherapy for first-line treatment of advanced non-small cell lung cancer: A systematic review and meta-analysis of randomized controlled trials (RCTs)
Presenter: Francis Mogollon-Duffo
Session: Poster Display session 1
Resources:
Abstract
2170 - Prognostic Impact of Metastatic Sites for Pembrolizumab Efficacy as First-line therapy in Patients with PD-L1 tumor proportion score (TPS) ≥ 50% Advanced Non–Small Cell Lung Cancer: A Retrospective Multicenter Study
Presenter: Hayato Kawachi
Session: Poster Display session 1
Resources:
Abstract
3051 - Impact of visceral fat area as independent predictive factor in patients with advanced non-small cell lung cancer treated with nivolumab
Presenter: Yuki Sato
Session: Poster Display session 1
Resources:
Abstract
3409 - Effect and safety of immune checkpoint inhibitors for brain metastases from non-small cell lung cancer
Presenter: Toshihiko Iuchi
Session: Poster Display session 1
Resources:
Abstract