scholarly journals Exploratory pooled analysis evaluating the effect of sequence of biological therapies on overall survival in patients with RAS wild-type metastatic colorectal carcinoma

ESMO Open ◽  
2018 ◽  
Vol 3 (2) ◽  
pp. e000297 ◽  
Author(s):  
Marc Peeters ◽  
Frédéric Forget ◽  
Meinolf Karthaus ◽  
Manuel Valladares-Ayerbes ◽  
Alberto Zaniboni ◽  
...  
Keyword(s):  
Overall Survival ◽  
Growth Factor ◽  
Colorectal Carcinoma ◽  
Growth Factor Receptor ◽  
Second Line ◽  
Wild Type ◽  
Metastatic Colorectal Carcinoma ◽  
First Line ◽  
Optimal Sequence ◽  
Link Type

BackgroundThe aim of this study was to evaluate the optimal sequence of targeted therapies (epidermal growth factor receptor inhibitors (EGFRi) and vascular endothelial growth factor inhibitors (VEGFi)), combined with chemotherapy, in patients with RAS wild-type (WT) metastatic colorectal carcinoma (mCRC). Exploratory analyses of overall survival (OS) for patients treated with either first-line panitumumab (EGFRi) and second-line VEGFi therapy, or first-line bevacizumab (VEGFi) and second-line EGFRi, were conducted.MethodsPatients from PEAK (NCT00819780), PRIME (NCT00364013) and Study 181 (NCT00339183), with RAS WT or RAS WT/BRAF WT tumours, were included in the analyses. OS data were pooled for patients receiving first-line panitumumab (PEAK and PRIME) or first-line bevacizumab (PEAK and 181), followed by second-line VEGFi or EGFRi, respectively.ResultsOverall, 104 RAS WT patients were included (n=66 panitumumab→VEGFi, n=38 bevacizumab→EGFRi). At the time of final data analysis, 63.6% versus 92.1% of patients in the panitumumab→VEGFi versus bevacizumab→EGFRi arms had died; median OS was 36.8 versus 27.8 months, respectively (HR 0.65; 95% CI 0.42 to 1.03). The OS HR for patients with RAS WT/BRAF WT mCRC overall was 0.58 (95% CI 0.36 to 0.95) and was 0.56 (95% CI 0.30 to 1.04) in those with left-sided tumours.ConclusionAlthough numbers are small, these exploratory analyses suggest a trend towards improved OS for first-line panitumumab plus chemotherapy followed by second-line VEGFi, compared with first-line bevacizumab followed by second-line EGFRi in patients with RAS WT and RAS WT/BRAF WT mCRC. Large prospective randomised trials are needed to further evaluate the optimum sequence of EGFRi/VEGFi in mCRC.

scholarly journals Chemotherapy versus erlotinib as second-line treatment in patients with advanced non-small cell lung cancer and wild-type epidermal growth factor receptor: an individual patient data (IPD) analysis

ESMO Open ◽  
2018 ◽  
Vol 3 (6) ◽  
pp. e000327
Author(s):  
Marina Chiara Garassino ◽  
Tomoya Kawaguchi ◽  
Vanesa Gregorc ◽  
Eliana Rulli ◽  
Masahiko Ando ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Individual Patient Data ◽  
Growth Factor Receptor ◽  
Line Treatment ◽  
Second Line ◽  
Wild Type ◽  
Mean Survival Time ◽  
Epidermal Growth

The efficacy of second-line treatment in patients with epidermal growth factor receptor (EGFR) wild-type tumours is still debatable. We assessed the efficacy of a standard second-line chemotherapy compared with erlotinib in an individual patient data approach for meta-analysis. The primary endpoint was overall survival (OS), and secondary endpoint was progression-free survival (PFS). Both were compared by log-rank test. The ‘restricted mean survival time’ (RMST) was estimated in each study and the difference in mean survival time up to the last available time point was calculated. The Cox proportional hazards model was used on survival analyses to provide HRs, to adjust for confounding variables and to test possible interaction with selected factors. Three randomised trials comparing chemotherapy versus erlotinib were analysed, including 587 randomised patients. Overall, 74% of patients included in the original trials were considered. 464 deaths and 570 progressions or deaths were observed. Compared with erlotinib, chemotherapy was associated to a decreased risk of progression (29%; HR: 0.71, 95% CI: 0.60 to 0.84, p< 0.0001;) but with no statistical significant reduction in OS (HR: 0.89, 95% CI: 0.74 to 1.06; p<0.20). No heterogeneity was found in both analyses. Patients treated with chemotherapy gained an absolute 1.5 and 1.6 months, respectively, in PFS and lifetime (RMST 95% CI: PFS 0.49 to 2.44; OS 95% CI: −1.04 to 4.25). These results showed that patients without a constitutively activated EGFR had better PFS with chemotherapy rather than with erlotinib while no statistical difference was observed in OS.

scholarly journals Phase III, Double-Blind, Randomized Trial That Compared Maintenance Lapatinib Versus Placebo After First-Line Chemotherapy in Patients With Human Epidermal Growth Factor Receptor 1/2–Positive Metastatic Bladder Cancer

2017 ◽  
Vol 35 (1) ◽  
pp. 48-55 ◽  
Author(s):  
Thomas Powles ◽  
Robert A. Huddart ◽  
Tony Elliott ◽  
Shah-Jalal Sarker ◽  
Charlotte Ackerman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
First Line ◽  
Her2 Positive ◽  
Epidermal Growth ◽  
Line Chemotherapy

Purpose To establish whether maintenance lapatinib after first-line chemotherapy is beneficial in human epidermal growth factor receptor (HER) 1/HER2–positive metastatic urothelial bladder cancer (UBC). Methods Patients with metastatic UBC were screened centrally for HER1/HER2 overexpression. Patients who screened positive for HER1/2 and who did not have progressive disease during chemotherapy (four to eight cycles) were randomly assigned one to one to lapatinib or placebo after completion of first-line/initial chemotherapy for metastatic disease. The primary end point was progression-free survival (PFS). Results Between 2007 and 2013, 446 patients with UBC were screened, and 232 with HER1- or HER2-positive disease were randomly assigned. The median PFS for lapatinib and placebo was 4.5 (95% CI, 2.8 to 5.4) and 5.1 (95% CI, 3.0 to 5.8) months, respectively (hazard ratio, 1.07; 95% CI, 0.81 to 1.43; P = .63). The overall survival for lapatinib and placebo was 12.6 (95% CI, 9.0 to 16.2) and 12.0 (95% CI, 10.5 to 14.9) months, respectively (hazard ratio, 0.96; 95% CI, 0.70 to 1.31; P = .80). Discontinuation due to adverse events were similar in both arms (6% lapatinib and 5% placebo). The rate of grade 3 to 4 adverse events for lapatinib and placebo was 8.6% versus 8.1% ( P = .82). Preplanned subset analysis of patients strongly positive for HER1/HER2 (3+ on immunohistochemistry; n = 111), patients positive for only HER1 (n = 102), and patients positive for only HER2 (n = 42) showed no significant benefit with lapatinib in terms of PFS and overall survival ( P > .05 for each). Conclusion This trial did not find significant improvements in outcome by the addition of maintenance lapatinib to standard of care.

scholarly journals Optimal Sequence and Second-Line Systemic Treatment of Patients with RAS Wild-Type Metastatic Colorectal Cancer: A Meta-Analysis

2021 ◽  
Vol 10 (21) ◽  
pp. 5166
Author(s):  
Chih-Chien Wu ◽  
Chao-Wen Hsu ◽  
Meng-Che Hsieh ◽  
Jui-Ho Wang ◽  
Min-Chi Chang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Meta Analysis ◽  
Second Line ◽  
Wild Type ◽  
First Line ◽  
Second Line Therapy ◽  
Optimal Sequence ◽  
First Line Therapy ◽  
Line Therapy

Although several sequential therapy options are available for treating patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC), the optimal sequence of these therapies is not well established. A systematic review and meta-analysis of 13 randomized controlled trials and 4 observational studies were performed, resulting from a search of the Cochrane Library, PubMed, and Embase databases. Overall survival (OS) did not differ significantly in patients with RAS-WT failure who were administered a second-line regimen of changed chemotherapy (CT) plus anti-epidermal growth factor receptor (EGFR) versus only changed CT, changed CT plus bevacizumab versus changed CT plus anti-EGFR, or changed CT versus maintaining CT plus anti-EGFR after first-line therapy with CT, plus bevacizumab. However, OS was significantly different with a second-line regimen that included changed CT plus bevacizumab, versus only changing CT. Analysis of first-line therapy with CT plus anti-EGFR for treatment of RAS-WT mCRC indicated that second-line therapy of changed CT plus an anti-EGFR agent resulted in better outcomes than changing CT without targeted agents. The pooled data study demonstrated that the optimal choice of second-line treatment for improved OS was an altered CT regimen with retention of bevacizumab after first-line bevacizumab failure. The best sequence for first-to-second-line therapy of patients with RAS-WT mCRC was cetuximab-based therapy, followed by a bevacizumab-based regimen.

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