Sanjay Popat1, Tony Mok2, James Chih-Hsin Yang3, Yi-Long Wu4, Juliane Lungershausen5, Uz Stammberger5, Ingolf Griebsch5, Tiago Fonseca6, Luis Paz-Ares7. 1. Royal Marsden Hospital, London, UK. Electronic address: sanjay.popat@rmh.nhs.uk. 2. State Key Laboratory of Southern China, Hong Kong Cancer Institute, The Chinese University of Hong Kong, Hong Kong. 3. National Taiwan University, Taipei, Taiwan. 4. Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China. 5. Boehringer Ingelheim GmbH, Ingelheim, Germany. 6. IMS Health, London, UK. 7. Instituto de Biomedicina de Sevilla - IBIS (University Hospital Virgen del Rocío, US, CSIC), Seville, Spain.
Abstract
OBJECTIVES: Epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) is a specific lung cancer subtype characterized by sensitivity to treatment with EGFR tyrosine kinase inhibitors (TKIs). Two reversible EGFR TKIs (gefitinib, erlotinib) and the irreversible ErbB family blocker afatinib are currently approved for treatment of EGFR mutation-positive NSCLC, but no head-to-head trials have been reported to date. We aimed to assess the relative efficacy of the three drugs by conducting a network meta-analysis (NMA). MATERIALS AND METHODS: A systematic literature review was conducted to identify all the available evidence. Outcomes of interest were progression-free survival (PFS) and overall survival. For PFS, results by investigator review were considered as not all trials assessed PFS independently. Results were analyzed using Bayesian methods. RESULTS: The literature search identified 246 articles that were assessed for eligibility, of which 21 studies were included in the NMA, including eight trials performed in an EGFR mutation-positive population. The estimated PFS HR (95% credible interval, CrI) for afatinib compared with gefitinib was 0.70 (0.40-1.16) and compared with erlotinib was 0.86 (0.50-1.50) in the total population. The estimated probability of being best for afatinib over all other treatments for PFS was 70% versus 27% for erlotinib and 3% for gefitinib; the estimated probability of chemotherapy being the best treatment was 0%. Estimated HR (95% CrI) in patients with common mutations was 0.73 (0.42-1.24) for afatinib compared with erlotinib and 0.60 (0.34-0.99) for afatinib compared with gefitinib. OS findings were not significantly different between treatments. CONCLUSIONS: In the absence of direct head-to-head trial data comparing efficacy between the three EGFR TKIs, our analysis suggests that afatinib is a viable treatment alternative to erlotinib or gefitinib in terms of PFS. A direct trial-based comparison of the efficacy of these agents is warranted to clarify their relative benefits.
OBJECTIVES:Epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) is a specific lung cancer subtype characterized by sensitivity to treatment with EGFR tyrosine kinase inhibitors (TKIs). Two reversible EGFR TKIs (gefitinib, erlotinib) and the irreversible ErbB family blocker afatinib are currently approved for treatment of EGFR mutation-positive NSCLC, but no head-to-head trials have been reported to date. We aimed to assess the relative efficacy of the three drugs by conducting a network meta-analysis (NMA). MATERIALS AND METHODS: A systematic literature review was conducted to identify all the available evidence. Outcomes of interest were progression-free survival (PFS) and overall survival. For PFS, results by investigator review were considered as not all trials assessed PFS independently. Results were analyzed using Bayesian methods. RESULTS: The literature search identified 246 articles that were assessed for eligibility, of which 21 studies were included in the NMA, including eight trials performed in an EGFR mutation-positive population. The estimated PFS HR (95% credible interval, CrI) for afatinib compared with gefitinib was 0.70 (0.40-1.16) and compared with erlotinib was 0.86 (0.50-1.50) in the total population. The estimated probability of being best for afatinib over all other treatments for PFS was 70% versus 27% for erlotinib and 3% for gefitinib; the estimated probability of chemotherapy being the best treatment was 0%. Estimated HR (95% CrI) in patients with common mutations was 0.73 (0.42-1.24) for afatinib compared with erlotinib and 0.60 (0.34-0.99) for afatinib compared with gefitinib. OS findings were not significantly different between treatments. CONCLUSIONS: In the absence of direct head-to-head trial data comparing efficacy between the three EGFR TKIs, our analysis suggests that afatinib is a viable treatment alternative to erlotinib or gefitinib in terms of PFS. A direct trial-based comparison of the efficacy of these agents is warranted to clarify their relative benefits.
Authors: Katharina Schremser; Wolf H Rogowski; Sigrid Adler-Reichel; Amanda L H Tufman; Rudolf M Huber; Björn Stollenwerk Journal: Pharmacoeconomics Date: 2015-11 Impact factor: 4.981
Authors: Alexandra Pender; Isaac Garcia-Murillas; Sareena Rana; Rosalind J Cutts; Gavin Kelly; Kerry Fenwick; Iwanka Kozarewa; David Gonzalez de Castro; Jaishree Bhosle; Mary O'Brien; Nicholas C Turner; Sanjay Popat; Julian Downward Journal: PLoS One Date: 2015-09-28 Impact factor: 3.240