Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Apr 22:8:921-8.
doi: 10.2147/OTT.S82365. eCollection 2015.

Progression-free survival as a surrogate endpoint for overall survival in patients with third-line or later-line chemotherapy for advanced gastric cancer

Liya Liu  1 , Hao Yu  1 , Lihong Huang  1 , Fang Shao  1 , Jianling Bai  1 , Donghua Lou  1 , Feng Chen  1
Affiliations

Progression-free survival as a surrogate endpoint for overall survival in patients with third-line or later-line chemotherapy for advanced gastric cancer

Liya Liu et al. Onco Targets Ther. .

Abstract

Background: The correlation between overall survival (OS) and progression-free survival (PFS) has been evaluated in patients with metastatic or advanced gastric cancer who have received first-line and/or second-line chemotherapy. However, no corresponding analysis has been done for patients who have undergone third-line or later-line chemotherapy.

Methods: A total of 303 patients from the Phase II/III studies of apatinib were pooled (the Phase II study as a training data set, the Phase III study as a testing data set). Landmark analyses of PFS at 2 months from randomization were performed to minimize lead time bias. The Cox proportional hazard model was used to test for the significance effect of PFS rate at 2 months in predicting OS. Additionally, the PFS/OS correlations were evaluated by the normal induced copula (National Institute for Health and Care Excellence) estimation model.

Results: The median OS was 3.37 months (95% confidence interval 2.63-3.80) in patients who experienced progression at 2 months and 5.67 months in patients who did not (95% confidence interval 4.83-6.67; P<0.0001). Compared with patients who did not progress at 2 months, the adjusted hazard ratio for death was 3.39 (95% confidence interval 1.79-6.41; P<0.0001) for patients who experienced progression at 2 months. Moreover, the correlation of PFS/OS was 0.84 (95% confidence interval 0.74-0.90). Similar results were found in the testing data set.

Conclusion: These results indicate that PFS correlates strongly with OS, suggesting PFS may be a useful early endpoint for patients with advanced gastric cancer who have undergone third-line or later-line chemotherapy. These observations require prospective validation.

Keywords: gastric cancer; overall survival; progression-free survival; surrogate endpoint.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Kaplan–Meier survival curves by PFS at 2 months in the training data set (A) and in the testing data set (B). Abbreviation: PFS, progression-free survival.
See this image and copyright information in PMC

References

    1. Stewart BW, Wild CP. World Cancer Report 2014. International Agency for Research on Cancer; 2014. [Accessed March 25, 2015]. Available from: http://www.iarc.fr/en/publications/pdfs-online/wcr/ - PubMed
    1. Kang YK, Kang WK, Shin DB, et al. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009;20:666–673. - PubMed
    1. Koizumi W, Narahara H, Hara T, et al. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008;9:215–221. - PubMed
    1. Ajani JA, Buyse M, Lichinitser M, et al. Combination of cisplatin/S-1 in the treatment of patients with advanced gastric or gastroesophageal adenocarcinoma: results of noninferiority and safety analyses compared with cisplatin/5-fluorouracil in the First-Line Advanced Gastric Cancer Study. Eur J Cancer. 2013;49:3616–3624. - PubMed
    1. Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687–697. - PubMed