Exon 19 deletion association with progression-free survival compared to L858R mutation at exon 21 in treatment with first-line EGFR-TKIs: A meta-analysis of subgroup data from eight phase III randomized controlled trials.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 8107-8107 ◽  
Author(s):  
Wenhua Liang ◽  
Jin Sheng ◽  
Xuan Wu ◽  
Yaxiong Zhang ◽  
Shiyang Kang ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Controlled Trials ◽  
First Line ◽  
Free Survival ◽  
Randomized Controlled ◽  
Exon 19 Deletion ◽  
L858r Mutation ◽  
Egfr Tkis

scholarly journals Progression-free survival as a surrogate endpoint for overall survival in modern ovarian cancer trials: a meta-analysis

2018 ◽  
Vol 10 ◽  
pp. 175883591878850 ◽  
Author(s):  
Katrin M. Sjoquist ◽  
Sarah J. Lord ◽  
Michael L. Friedlander ◽  
Robert John Simes ◽  
Ian C. Marschner ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Surrogate Endpoint ◽  
Controlled Trials ◽  
First Line ◽  
Free Survival ◽  
Randomized Controlled ◽  
The Difference

Background: Progression-free survival (PFS) has been adopted as the primary endpoint in many randomized controlled trials, and can be determined much earlier than overall survival (OS). We investigated whether PFS is a good surrogate endpoint for OS in trials of first-line treatment for epithelial ovarian cancer (EOC), and whether this relationship has changed with the introduction of new treatment types. Methods: In a meta-analysis, we identified summary data [hazard ratio (HR) and median time] from published randomized controlled trials. Linear regression was used to assess the association between treatment effects on PFS and OS overall, and for subgroups defined by treatment type, postprogression survival (PPS) and established prognostic factors. Results: Correlation between HRs for PFS and OS, in 26 trials with 30 treatment comparisons comprising 24,870 patients, was modest ( r2 = 0.52, weighted by trial sample size). The correlation diminished with recency: preplatinum/paclitaxel era, r2 = 0.66; platinum/paclitaxel, r2 = 0.44; triplet combinations, r2 = 0.22; biologicals, r2 = 0.30. The median PPS increased over time for the experimental ( Ptrend = 0.03) and control arms ( Ptrend = 0.003). The difference in median PPS between treatment arms strongly correlated with the difference in median OS ( r2 = 0.83). In trials where the control therapy had median PPS of less than 18 months, correlation between PFS and OS was stronger ( r2 = 0.64) than where the median PPS was longer ( r2 = 0.48). Conclusions: In EOC, correlation in the relative treatment effect between PFS and OS in first-line platinum-based chemotherapy randomized controlled trials is moderate and has weakened with increasing availability of effective salvage therapies.

scholarly journals Efficacy and safety of first line treatments for patients with advanced epidermal growth factor receptor mutated, non-small cell lung cancer: systematic review and network meta-analysis

BMJ ◽  
2019 ◽  
pp. l5460 ◽  
Author(s):  
Yi Zhao ◽  
Jingting Liu ◽  
Xiuyu Cai ◽  
Zhenkui Pan ◽  
Jun Liu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Meta Analysis ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Combination Treatments ◽  
Exon 19 Deletion ◽  
Egfr Mutated

AbstractObjectiveTo compare the efficacy and safety of first line treatments for patients with advanced epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC).DesignSystematic review and network meta-analysis.Data sourcesPubMed, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and several international conference databases, from inception to 20 May 2019.Eligibility criteria for selecting studiesPublished and unpublished randomised controlled trials comparing two or more treatments in the first line setting for patients with advanced EGFR mutated NSCLC were included in a bayesian network meta-analysis. Eligible studies reported at least one of the following clinical outcome measures: progression free survival, overall survival, objective response rate, and adverse events of grade 3 or higher.Results18 eligible trials involved 4628 patients and 12 treatments: EGFR tyrosine kinase inhibitors (TKIs; osimertinib, dacomitinib, afatinib, erlotinib, gefitinib, and icotinib), pemetrexed based chemotherapy, pemetrexed free chemotherapy, and combination treatments (afatinib plus cetuximab, erlotinib plus bevacizumab, gefitinib plus pemetrexed based chemotherapy, and gefitinib plus pemetrexed). Consistent with gefitinib plus pemetrexed based chemotherapy (hazard ratio 0.95, 95% credible interval 0.72 to 1.24), osimertinib showed the most favourable progression free survival, with significant differences versus dacomitinib (0.74, 0.55 to 1.00), afatinib (0.52, 0.40 to 0.68), erlotinib (0.48, 0.40 to 0.57), gefitinib (0.44, 0.37 to 0.52), icotinib (0.39, 0.24 to 0.62), pemetrexed based chemotherapy (0.24, 0.17 to 0.33), pemetrexed free chemotherapy (0.16, 0.13 to 0.20), afatinib plus cetuximab (0.44, 0.28 to 0.71), and gefitinib plus pemetrexed (0.65, 0.46 to 0.92). Osimertinib and gefitinib plus pemetrexed based chemotherapy were also consistent (0.94, 0.66 to 1.35) in providing the best overall survival benefit. Combination treatments caused more toxicity in general, especially erlotinib plus bevacizumab, which caused the most adverse events of grade 3 or higher. Different toxicity spectrums were revealed for individual EGFR-TKIs. Subgroup analyses by the two most common EGFR mutation types indicated that osimertinib was associated with the best progression free survival in patients with the exon 19 deletion, and gefitinib plus pemetrexed based chemotherapy was associated with the best progression free survival in patients with the Leu858Arg mutation.ConclusionsThese results indicate that osimertinib and gefitinib plus pemetrexed based chemotherapy were associated with the best progression free survival and overall survival benefits for patients with advanced EGFR mutated NSCLC, compared with other first line treatments. The treatments resulting in the best progression free survival for patients with the exon 19 deletion and Leu858Arg mutations were osimertinib and gefitinib plus pemetrexed based chemotherapy, respectively.Systematic review registrationPROSPERO CRD42018111954.

Clinical Equipoise for Trials of Novel Biologic Therapies, Therapeutic Success Rates, and Predictors of Success: A Meta-Analysis

2017 ◽  
pp. 1-12
Author(s):  
Doah Cho ◽  
Felicia T. Roncolato ◽  
Johnathan Man ◽  
John Simes ◽  
Sarah J. Lord ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Predictors Of Success ◽  
Biologic Therapies ◽  
Therapeutic Success ◽  
Free Survival ◽  
Randomized Controlled ◽  
Phase Iii Trials

Purpose The demand for more rapid access to novel biologic therapies than randomized controlled trials can deliver is a topic of ongoing study and debate. We aimed to inform this debate by estimating therapeutic success from phase III trials comparing novel biologic therapies with standard of care and identifying predictors of success. Methods This was a meta-analysis of phase III trials evaluating novel biologic therapies in advanced breast, colorectal, lung, and prostate cancers. Therapeutic success was defined as statistically significant results for the primary end point favoring novel biologic therapies. Results Of 119 included phase III trials (76,726 patients), therapeutic success was 41%, with a statistically significant relative reduction in disease progression and death for novel biologic therapies over standard of care of 20% and 8%. Therapeutic success did not improve over time (pre-2010, 33%; 2010 to 2014, 44%; P = .2). Predictors of success were a biomarker-selected population (odds ratio, 4.74; 95% CI, 2.05 to 10.95) and progression-free survival end point compared with overall survival (odds ratio, 5.22; 95% CI, 2.41 to 11.39). Phase III trials with a biomarker-selected population showed a larger 28% progression-free survival benefit than phase III trials overall (hazard ratio, 0.72; 95% CI, 0.70 to 0.75) but similar 8% overall survival benefit (hazard ratio, 0.92; 95% CI, 0.90 to 0.94). Therapeutic success of phase III trials with and without a preceding phase II trial were 43% and 30%, respectively Conclusion Therapeutic success of novel biologic therapies in phase III trials, including therapies with a matching predictive biomarker, was modest and has not significantly improved over time. Equipoise remains and supports the ongoing ethical and scientific requirement for phase III randomized controlled trials to estimate treatment efficacy and assess the value of potential biomarkers.

scholarly journals Indirect analysis of first-line therapy for advanced non-small-cell lung cancer with activating mutations in the Japanese population

2020 ◽  
Author(s):  
Kazuhiko Nakagawa ◽  
Koichi Matsumura ◽  
Tayler Scory ◽  
Megan S Farris ◽  
Kelly A Larkin-Kaiser ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Meta Analysis ◽  
Small Cell ◽  
Controlled Trials ◽  
Small Cell Lung ◽  
First Line ◽  
Randomized Controlled ◽  
Egfr Tkis

Background: Five EGFR-tyrosine kinase inhibitors ( EGFR TKIs) are currently available in the first-line setting for non-small-cell lung cancer (NSCLC) in Japan. The aim here was to compare the relative efficacy of EGFR TKIs in the Japanese population. Materials & methods: A systematic review identified randomized controlled trials examining the efficacy of first-line EGFR TKIs. A Bayesian network meta-analysis was used to assess these EGFR TKI comparisons for progression-free survival (PFS). Results: A total of seven randomized controlled trials were identified and considered for network meta-analysis. Dacomitinib showed a trend toward improved PFS versus all comparators. Conclusion: Dacomitinib demonstrated a trend toward improved PFS and therefore, should be considered one of the standard first-line therapies for Japanese patients diagnosed with EGFR+ non-small-cell lung cancer.

Efficacy of gefitinib in patients with advanced non-small cell carcinoma of the lung harboring common, uncommon and complex EGFR mutations

2021 ◽  
Vol 08 ◽  
Author(s):  
Wang Chun Kwok ◽  
Ka Yan Chiang ◽  
James Chung Man Ho ◽  
Terence Chi Chun Tam ◽  
Mary Sau Man Ip ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Small Cell ◽  
Egfr Mutations ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
Exon 19 Deletion ◽  
L858r Mutation ◽  
First Line Treatment ◽  
Exon 19

Background: As the commonest EGFR-TKI being used in Hong Kong, gefitinib has shown to be efficacious and safe as first line treatment for L858R mutation and exon 19 deletion with less gastrointestinal and cutaneous adverse events than erlotinib and afatinib. However, the evidence for therapeutic efficacy for uncommon and complex EGFR mutations is lacking. Whether gefitinib is efficacious for uncommon and complex EGFR mutations worth studying. Objectives: To assess the therapeutic efficacy of gefitinib, as measured by progression-free survival and overall survival, among advanced stage lung cancer patients with common, uncommon and complex EGFR mutations. Methods: This is a retrospective cohort study that included 241 Chinese patients with advanced non-small cell carcinoma of lung harboring EGFR mutations and received gefitinib 250 mg daily as first-line treatment. The progression-free survival [PFS] and overall survival [OS] for patients with different EGFR mutations, namely exon 19 deletion, L858R mutation in exon 21, uncommon EGFR mutations and complex EGFR mutations were analyzed. Results: Among the 241 patients, 118 [49%] had exon 19 deletion, 104 [43%] had L858R mutation in exon 21, 6 [2.5%] had uncommon EGFR mutations, 13 [5.4%] had complex EGFR mutations. The mean age was 69. 72% of the patients were female and with 81% being non-smoker. For patients with complex EGFR mutations, regardless of the presence of exon 19 deletion and L858R mutation as the component, have better PFS and OS than patients with single common EGFR mutations [Exon 19 deletion or L858R mutation]. Patients with uncommon EGFR mutations have inferior PFS and OS than those with common EGFR mutations. Conclusion: Gefitinib is a possible option for patients with complex EGFR mutations while it may not be the preferred treatment option in patients with single uncommon EGFR mutations.

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