Cancer Chemotherapy and Pharmacology (2018) 81:981–989
Survival impact of post-progression chemotherapy in advanced
gastric cancer: systematic review and meta-analysis
· Atsuo Takashima
· Kentaro Sakamaki
· Satoshi Morita
· Narikazu Boku
Received: 27 December 2017 / Accepted: 22 March 2018 / Published online: 29 March 2018
© Springer-Verlag GmbH Germany, part of Springer Nature 2018
Purpose We conducted a systematic review and meta-analysis on survival impact of post-progression chemotherapy (post-
Cx) after ﬁrst-line chemotherapy (1st-Cx) and after second-line chemotherapy (2nd-Cx), and survival beneﬁt of third-line
chemotherapy (3rd-Cx) for advanced gastric cancer (AGC).
Methods Phase III trials of systemic chemotherapy for AGC published in English between 2005 and 2015 or presented at
annual meetings of ASCO or ESMO between 2013 and 2015 were searched. Numbers of patients, types of chemotherapy,
patient baseline, proportion of patients receiving post-Cx (post-Cx%), median progression-free survival (mPFS), and median
overall survival (mOS) of each treatment arm were surveyed; trials not reporting these parameters were excluded. Median
post-progression survival (mPPS) was calculated as the diﬀerence between mOS and mPFS. Weighted Spearman’s cor-
relation coeﬃcients between post-Cx% and survival outcomes (mOS and mPPS) were calculated. The eﬀect of post-Cx%
on survival outcomes adjusted for the types of chemotherapy and patient characteristics was evaluated by meta-regression.
Results Overall, 25 phase III trials of AGC were selected: 15 trials with 31 arms for 1st-Cx, and 10 trials with 16 arms
for 2nd-Cx. Weighted Spearman’s correlation coeﬃcients for post-Cx% and mOS/mPPS were 0.520/0.739 for 1st-Cx, and
0.767/0.823 for 2nd-Cx. Meta-regression analyses adjusting for types of chemotherapy, age, and PS showed that a 10%
increase in post-Cx% was associated with prolongation of mOS by 1.033 months for 1st-Cx and 0.344 months for 2nd-Cx.
Conclusions Post-Cx% both after 1st-Cx and 2nd-Cx were correlated with mOS/mPPS, suggesting a survival beneﬁt of
3rd-Cx in addition to that of 2nd-Cx for AGC.
Keywords Gastric cancer · Post-progression survival · First-line chemotherapy · Second-line chemotherapy · Third-line
Gastric cancer is one of the most common malignant dis-
eases in the world and caused 951,000 cases and 723,000
deaths worldwide in 2012 . Despite recent progress in the
treatment, advanced gastric cancer (AGC) remains incur-
able, and its standard treatment is palliative chemotherapy.
A systematic review showed survival beneﬁts of ﬁrst-line
chemotherapy over best supportive care (BSC) . As for
second-line chemotherapy, several phase III trials demon-
strated a survival beneﬁt of monotherapy with docetaxel and
irinotecan over BSC [3–5]. In addition, eﬃcacy of ramu-
cirumab with or without paclitaxel in second-line chemo-
therapy was demonstrated in phase III trials (RAINBOW
 and REGARD , respectively).
In addition to the first- and second-line chemother-
apy, some studies have suggested a beneﬁt of third-line
Electronic supplementary material The online version of this
article (https ://doi.org/10.1007/s0028 0-018-3569-9) contains
supplementary material, which is available to authorized users.
* Atsuo Takashima
Department of Gastrointestinal Medical Oncology,
National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku,
Tokyo 104-0045, Japan
Department of Medicine, Keio University Graduate School
of Medicine, Tokyo, Japan
Department of Biostatistics and Bioinformatics, University
of Tokyo Graduate School of Medicine, Tokyo, Japan
Department of Biomedical Statistics and Bioinformatics,
Kyoto University Graduate School of Medicine, Kyoto, Japan