Pei Ni Ding1, Sarah J Lord2, Val Gebski3, Matthew Links4, Victoria Bray5, Richard J Gralla6, James Chih-Hsin Yang7, Chee Khoon Lee8. 1. National Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Sydney, Australia; Department of Medical Oncology, Liverpool Hospital, Sydney, Australia. 2. National Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Sydney, Australia; School of Medicine, The University of Notre Dame, Sydney, Australia. 3. National Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Sydney, Australia. 4. Cancer Care Centre, St. George Hospital, Sydney, Australia. 5. Department of Medical Oncology, Liverpool Hospital, Sydney, Australia. 6. Albert Einstein College of Medicine, Jacobi Medical Center, New York, New York. 7. Graduate Institute of Oncology, National Taiwan University and Department of Oncology, National Taiwan University Hospital, Taipei, Republic of China. 8. National Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Sydney, Australia; Cancer Care Centre, St. George Hospital, Sydney, Australia. Electronic address: chee.lee@ctc.usyd.edu.au.
Abstract
INTRODUCTION: Gefitinib, erlotinib, and afatinib are tyrosine kinase inhibitors (TKIs) used for treatment of advanced EGFR-mutated NSCLC. Estimating differences in toxicity between these EGFR TKIs is important for personalizing treatment. METHODS: We performed a meta-analysis of randomized trials that compared EGFR TKI therapy against chemotherapy or placebo. We extracted data from the EGFR TKI arm for indirect comparisons to estimate the relative risk for toxic death, grade 3 to 4 (G3/4) adverse events (AEs), and discontinuation of treatment because of AE for each EGFR TKI. RESULTS: Sixteen trials included 2535 patients with mutated or wild-type EGFR. Toxic deaths were rare (1.7%), with pneumonitis being most frequent cause and no significant differences between EGFR TKIs. Overall, 40% of patients experienced G3/4 AEs. The risk for G3/4 AEs was lower with gefitinib (29.1%) than with erlotinib (54.1%) or afatinib (42.1%) (p < 0.01). Discontinuation of treatment because of AEs occurred in 7.7% of patients, with no significant differences between EGFR TKIs. Diarrhea (in 53.3% of cases) and rash (in 66.5%) were the most frequent AEs. The risk for rash was higher with afatinib (84.8%) than with erlotinib (62.0%) or gefitinib (62.0%) (p < 0.01). The risk for diarrhea was higher with afatinib (91.7%) than with erlotinib (42.4%) or gefitinib (44.4%) (p < 0.01). The risk for increased liver enzyme levels was higher with gefitinib (61.7%) than with erlotinib (17.8%) or afatinib (20.1%) (p < 0.01). A risk-benefit contour was used to assess the trade-off between efficacy and toxicity for different EGFR TKIs. CONCLUSIONS: EGFR TKIs are well tolerated, with less than 10% of patients discontinuing treatment because of AEs. The profile of and risk for toxicities vary between EGFR TKIs and can be used to inform the selection of treatment.
INTRODUCTION:Gefitinib, erlotinib, and afatinib are tyrosine kinase inhibitors (TKIs) used for treatment of advanced EGFR-mutated NSCLC. Estimating differences in toxicity between these EGFR TKIs is important for personalizing treatment. METHODS: We performed a meta-analysis of randomized trials that compared EGFR TKI therapy against chemotherapy or placebo. We extracted data from the EGFR TKI arm for indirect comparisons to estimate the relative risk for toxic death, grade 3 to 4 (G3/4) adverse events (AEs), and discontinuation of treatment because of AE for each EGFR TKI. RESULTS: Sixteen trials included 2535 patients with mutated or wild-type EGFR. Toxic deaths were rare (1.7%), with pneumonitis being most frequent cause and no significant differences between EGFR TKIs. Overall, 40% of patients experienced G3/4 AEs. The risk for G3/4 AEs was lower with gefitinib (29.1%) than with erlotinib (54.1%) or afatinib (42.1%) (p < 0.01). Discontinuation of treatment because of AEs occurred in 7.7% of patients, with no significant differences between EGFR TKIs. Diarrhea (in 53.3% of cases) and rash (in 66.5%) were the most frequent AEs. The risk for rash was higher with afatinib (84.8%) than with erlotinib (62.0%) or gefitinib (62.0%) (p < 0.01). The risk for diarrhea was higher with afatinib (91.7%) than with erlotinib (42.4%) or gefitinib (44.4%) (p < 0.01). The risk for increased liver enzyme levels was higher with gefitinib (61.7%) than with erlotinib (17.8%) or afatinib (20.1%) (p < 0.01). A risk-benefit contour was used to assess the trade-off between efficacy and toxicity for different EGFR TKIs. CONCLUSIONS:EGFR TKIs are well tolerated, with less than 10% of patients discontinuing treatment because of AEs. The profile of and risk for toxicities vary between EGFR TKIs and can be used to inform the selection of treatment.
Authors: René J Boosman; Jacobus A Burgers; Egbert F Smit; Neeltje Steeghs; Anthonie J van der Wekken; Jos H Beijnen; Alwin D R Huitema; Rob Ter Heine Journal: Drugs Date: 2021-12-11 Impact factor: 9.546
Authors: Xiaoran Yin; Yanan Cui; Richard S Kim; Wesley R Stiles; Seung Hun Park; Haoran Wang; Li Ma; Lin Chen; Yoonji Baek; Satoshi Kashiwagi; Kai Bao; Amy Ulumben; Takeshi Fukuda; Homan Kang; Hak Soo Choi Journal: Theranostics Date: 2022-05-13 Impact factor: 11.600
Authors: Angel Y F Kam; Sadhna O Piryani; Chang-Lung Lee; David A Rizzieri; Neil L Spector; Stefanie Sarantopoulos; Phuong L Doan Journal: Mol Cancer Res Date: 2021-01-29 Impact factor: 6.333
Authors: A S M Ashique Mahmood; Shruti Rao; Peter McGarvey; Cathy Wu; Subha Madhavan; K Vijay-Shanker Journal: PLoS One Date: 2017-12-20 Impact factor: 3.240
Authors: John Glod; Fernanda I Arnaldez; Lori Wiener; Melissa Spencer; J Keith Killian; Paul Meltzer; Eva Dombi; Claudia Derse-Anthony; Joanne Derdak; Ramaprasad Srinivasan; W Marston Linehan; Markku Miettinen; Seth M Steinberg; Lee Helman; Brigitte C Widemann Journal: Clin Cancer Res Date: 2019-08-22 Impact factor: 12.531