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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

3327 - Evaluation of Progression-Free Survival (PFS) and One-Year (1y) Survival as Surrogate Endpoints (SE) in Previously Treated Advanced Non-Small Cell Lung Cancer (adNSCLC) in the Era of Immuno-Oncology (IO)

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Topics

Targeted Therapy;  Immunotherapy

Tumour Site

Presenters

Shen Zhao

Citation

Annals of Oncology (2018) 29 (suppl_8): viii493-viii547. 10.1093/annonc/mdy292

Authors

S. Zhao, Z. Zhang, T. Zhou, Y. Zhang, L. Zhang

Author affiliations

  • Medical Oncology, Sun Yat-sen University Cancer Center, 510060 - Guangzhou/CN
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Resources

Abstract 3327

Background

The advent of IO has led to greater availability of effective subsequent treatments and extended survival of patients, increasingly complicating the evaluation of overall survival (OS) in adNSCLC trials. To expedite drug developments and allow timely approvals of potentially effective agents for previously treated adNSCLC, we assessed the validity of PFS and 1y survival as SE in 2nd-line adNSCLC trials, especially in those containing immunotherapies.

Methods

We conducted a systemic literature search of 2nd-line adNSCLC trials. A weighted linear regression analysis between post 2nd-line treatments and OS was performed to establish the necessity of SE in 2nd-line trials. Adopting Buyse’s criteria for surrogacy, a two-stage meta-analytic validation model was used to assess associations between SE and OS at patient-level and trial-level. The strength of association was quantified by the coefficient of determination (R2). R2 >0.6 was defined a priori as clinically relevant. Results were validated with leave-one-out cross validation methods.

Results

Of 1680 studies identified, 85 trials with 146 arms and 25,698 patients were included. Data of 22,804 patients from 50 trials (103 arms) were used for surrogacy assessment. A significant correlation between percentages of post 2nd-line treatments and OS improvements was identified (R2 [95% confidence interval] =0.347 [0.345-0.351], PPearson <0.0001, PSpearman <0.0001). PFS showed weak patient-level (0.100 [0.098-0.101]) and trial-level (0.064 [0.059-0.069]) associations with OS, while 1y survival strongly correlated with OS at both levels (R2patient=0.707 [0.704-0.708]; R2trial=0.829 [0.828-0.831]). Subgroup analysis of IO trials yielded similar results (PFS: R2patient=0.177 [0.128-0.200], R2trial=0.835 [0.791-0.918]; 1y survival: R2patient=0.965 [0.960-0.968], R2trial=0.778 [0.734-0.856]).

Conclusions

A valid SE is needed in 2nd-line adNSCLC trials in the era of IO. PFS poorly correlated with OS at both patient-level and trial-level, while 1y survival showed the potential of being a valid SE in future 2nd-line adNSCLC trials.

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Editorial Acknowledgement

Not applicable.

Disclosure

All authors have declared no conflicts of interest.

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