Chemotherapy or Targeted Therapy as Second-Line Treatment of Advanced Gastric Cancer. A Systematic Review and Meta-Analysis of Published Studies

Abstract

Chemotherapy is a cornerstone in treatments of gastric cancer, but despite its benefit, less than 60% of patients receive salvage therapy in clinical practice. We performed a systematic review and meta-analysis based on trial data on the role of second-line treatment of advanced gastric cancer. MEDLINE/PubMed and Cochrane Library were searched for randomized phase III trials that compared active therapy to best supportive care in advanced gastric cancer. Data extraction was conducted according to the PRISMA statement. Summary HR for OS was calculated using a hierarchical Bayesian model and subgroup analysis was performed based on baseline Eastern Cooperative Oncology Group Performance Status (ECOG) performance status (0 vs. 1 or more). A total of 1,407 patients were evaluable for efficacy, 908 were treated in the experimental arms, with chemotherapy (231 pts) or with targeted therapies (677 pts). The risk of death was decreased by 18% (HR = 0.82; 95% CI, 0.79–0.85; posterior probability HR≥1: <0.00001) with active therapies. Chemotherapy and ramucirumab were able to decrease this risk by 27% and 22%, respectively. No differences were found between chemotherapy and ramucirumab. In patients with ECOG = 0 a greater benefit was found for chemotherapy with a reduction of the risk of death by 43% and no benefits were found for ramucirumab or everolimus. In patients with ECOG = 1 or more a significant reduction of the risk of death by 32% was reported in patients treated with ramucirumab, even if no significant difference was reported between chemotherapy and ramucirumab. This analysis reports that active and available therapies are able to prolong survival in patients with advanced gastric cancer with a different outcome based on initial patient’s performance status. New trials based on a better patient stratification are awaited.

Real-world treatment patterns among patients with advanced gastric cancer in South Korea.

“…Performance status was reported to be a predictor of response to chemotherapy [17]. A recent metaanalysis suggests that patients with PS 0 have better survival after chemotherapy than those with PS 1 [18]. Among patients who received second-line therapy in the present study, 61.6% discontinued treatment because of disease progression and 46 patients (23.2%) received third-line treatment, highlighting the need for more clinical trials in advanced gastric cancer.…”

“…Other recent studies have reported a survival advantage associated with treatment with a second-line taxane such as docetaxel, or with irinotecan for cancers refractory to fluoropyrimidine and platinum treatment when compared to BSC [13,14]. In addition, no single agent option has been shown to be better than another in the second-line setting [18,23]. In our data, there appeared to be a trend in the increased use of taxanes as second-line therapy in 2012 relative to earlier years of the study (2009-2011); however, taxanes were prescribed to less than 20% of patients.…”

A systematic review and meta-analysis of randomized trials on the role of targeted therapy in the management of advanced gastric cancer: Evidence does not translate?

“…10,[16][17][18] Concerning the second-line treatment, available data on the safety and efficacy of therapy are limited. 19 In particular COUGAR-02, a phase III randomized clinical trial, reported a significant OS improvement for docetaxel versus best supportive care (BSC) with a median advantage of 1.5 months. 20 Regarding subsequent lines of treatment, BSC or recruitment in clinical trials (fit patients only) is considered as the best choice.…”

“…27 At least one data-comparison in terms of survival, RR, or toxicity was reported in all selected RCTs, which were therefore deemed eligible for the end-point analysis. Summarizing the 22 trials included in final analyses: 19 were eligible for OS analysis (among them, we underlined, that: 9 were included in antiangiogenic analysis; 4 studies were included in anti-EGFR analysis; 3 studies were included in anti-HER2 analysis; single trials respectively investigating a MET inhibitor, mTOR inhibitor and a PARP inhibitor), 19 were eligible for PFS analysis (among them, we underlined, that: 10 were included in anti-angiogenic analysis; 4 studies were included in anti-EGFR analysis; 2 studies were included in anti-HER2 analysis; single trials respectively investigating a MET inhibitor, mTOR inhibitor and a PARP inhibitor), and 19 were evaluable for RR analysis (among them, we underlined, that: 9 were included in anti-angiogenic analysis; 4 studies were included in anti-EGFR analysis; 3 studies were included in anti-HER2 analysis; single trials respectively investigating a Hedgehog inhibitor, a mTOR inhibitor and a PARP inhibitor). Twenty studies were evaluable for toxicity.…”

Results of the use of ramucirumab in combination with paclitaxel or ramucirumab monotherapy as the second line treatment in patients with disseminated HER2-negative gastric or cardioesophageal junction adenocarcinoma: experience of N.N. Blokhin russian cancer research center of the ministry of health of Russia

“…Число больных, которым назначают вторую линию лечения, варьирует в широком диапазоне. Если в исследовании REAL-2 доля пациентов, получивших вто-рую линию лечения, составила 14% [3], то в исследовании SPIRITS -75% [4], в повседневной практике эта цифра колеблется около 45% [5].…”