Risk of Treatment-Related Toxicities from EGFR Tyrosine Kinase Inhibitors: A Meta-analysis of Clinical Trials of Gefitinib, Erlotinib, and Afatinib in Advanced EGFR -Mutated Non–Small Cell Lung Cancer

Ding, Pei Ni; Lord, Sarah J.; Gebski, Val; Links, Matthew; Bray, Victoria; Gralla, Richard J.; Yang, James Chih‐Hsin; Lee, Chee Khoon

doi:10.1016/j.jtho.2016.11.2236

Cited by 132 publications

(100 citation statements)

References 33 publications

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“…Of the nine patients that discontinued afatinib treatment, diarrhea was the cause in four (44.4%). In meta‐analyses of clinical trials, the risk of afatinib‐induced diarrhea was significantly higher with afatinib (91.7%) than with erlotinib (42.4%) or gefitinib (44.4%) . Numerous pollutant studies have focused on the relationship between afatinib dose and toxicity.…”

Section: Discussionmentioning

confidence: 99%

“…In the LUX‐Lung 7 trial, afatinib significantly improved PFS and the time to treatment failure compared to gefitinib . However, higher rates of severe adverse events (AEs), such as diarrhea, skin rash, paronychia, and stomatitis, were reported compared to first‐generation EGFR‐TKIs . Appropriate management of AEs and dose reduction of afatinib are important for EGFR ‐positive NSCLC patients.…”

Section: Introductionmentioning

confidence: 99%

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Clinical analysis of EGFR‐positive non‐small cell lung cancer patients treated with first‐line afatinib: A Nagano Lung Cancer Research Group

et al. 2019

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Background In the LUX‐Lung 3 and LUX‐Lung 6 trials, afatinib improved overall survival in previously untreated patients with EGFR 19del mutated non‐small cell lung cancer (NSCLC) compared to chemotherapy. The appropriate management of adverse events and dose reduction of afatinib are important for EGFR‐ positive NSCLC patients. We conducted a retrospective and observational study of patients treated with first‐line afatinib for EGFR‐ positive NSCLC in Nagano prefecture, Japan, focusing on efficacy and toxicities. Methods We retrospectively collected the medical records of NSCLC patients initially treated with afatinib between May 2014 and March 2018. Results A total of 62 patients with a median age of 67 years and a median body surface area (BSA) of 1.57 m 2 were included. The overall response rate was 87.7% and median progression‐free survival (PFS) was 15.7 months. The median PFS was similar between standard initial dose (40 mg) and reduced initial doses (30 and 20 mg) (15.7 vs. 14.2 months; P = 0.978). The frequency of dose reduction and the discontinuation rate in the 40 mg daily dose group was higher in patients with BSA < 1.58 m 2 (100%) compared to BSA ≥ 1.58 m 2 (68.2%) ( P = 0.014). The frequency of diarrhea was higher in patients with BSA < 1.58 m 2 (93.5%) compared to BSA ≥ 1.58 m 2 (71.0%) ( P = 0.02). Conclusion In real‐world clinical practice, first‐line afatinib was well managed and was equally as effective as in previous clinical trials of EGFR ‐positive NSCLC. BSA is considered a predictive marker for appropriate afatinib dose reduction.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical analysis of EGFR‐positive non‐small cell lung cancer patients treated with first‐line afatinib: A Nagano Lung Cancer Research Group

et al. 2019

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“…However, some patients experience AEs and do not wish to continue treatment using the same drug. For example, two studies of patients with EGFR mutation‐positive NSCLC indicated that 6.1‐7.7% of patients refused to continue EGFR‐TKI treatment because of various AEs such as ILD and hepatitis . Although there are some case reports describing successful EGFR‐TKI rechallenge after recovery from EGFR‐TKI‐induced AEs, few studies have examined switching EGFR‐TKIs because of AEs, rather than PD.…”

Section: Discussionmentioning

confidence: 99%

“…These drugs include gefitinib, erlotinib, and afatinib, which provide response rates of approximately 60‐70% and a median progression‐free survival (PFS) of approximately 12 months . However, a small proportion of patients with NSCLC and EGFR mutations discontinue EGFR‐TKI therapy because of adverse events (AEs) . In clinical practice, one approach to this development is switching from one EGFR‐TKI to another.…”

Section: Introductionmentioning

confidence: 99%

The effects of switching EGFR‐TKI treatments for non‐small cell lung cancer because of adverse events

Sakata

Kawamura

Shingu

et al. 2018

Asia-Pac J Clncl Oncology

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Background Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) are used to treat patients with non‐small cell lung cancer (NSCLC) and EGFR driver mutations. Although some patients discontinued these treatments because of adverse events, it is unclear whether switching EGFR‐TKI because of adverse events provides a benefit. Methods This retrospective study evaluated data from 22 patients with EGFR mutation‐positive NSCLC who received at least two EGFR‐TKIs that were switched because of adverse events (March 2011 to September 2017). Progression‐free survival 2 (PFS2) was defined as the time from starting of the first EGFR‐TKI treatment to disease progression during the second EGFR‐TKI treatment. Results Seventeen patients received gefitinib as the first EGFR‐TKI treatment, while four patients received afatinib and one patient received erlotinib. The median time to failure of the first EGFR‐TKI treatment was 1.6 months. The EGFR‐TKIs were switched because of hepatotoxicity (n = 16), interstitial lung disease (n = 3), and other reasons (n = 3). The median washout period was 1.1 months. Seventeen patients received erlotinib as the second EGFR‐TKI treatment, while three patients received gefitinib and two patients received afatinib. The median PFS for the second EGFR‐TKI treatment was 15.2 months. The median PFS2 was 17.7 months and the median overall survival was 32.8 months. Conclusions Switching EGFR‐TKIs because of adverse events provided a clinical benefit for patients with EGFR mutation‐positive NSCLC. Appropriate judgment regarding switching from one EGFR‐TKI to another may improve the performance status and prognosis of patients with EGFR mutation‐positive NSCLC.

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“…As regards toxicity, skin rash and diarrhea were the most common adverse events (AEs) reported with all EGFR-TKIs, with a higher percentage observed with afatinib than erlotinib or gefitinib, while the risk of elevated transaminases was higher for gefitinib compared to the other TKIs. The percentage of grade (G) 3-4 AEs was higher with erlotinib (54.1%), than afatinib (42.1%) or gefitinib (29.1%), while no differences in drug-related AEs discontinuation has been observed between the different TKIs (Ding et al, 2016). Furthermore the safety profiles of all three EGFRTKIs became similar if evaluated after an immediate and proactive management of emerging toxicities (Passaro et al, 2014).…”

Section: Indirect Comparisonsmentioning

confidence: 93%

EGFR inhibition in NSCLC: New findings…. and opened questions?

Passiglia

Listì

Castiglia

et al. 2017

Critical Reviews in Oncology/Hematology

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The targeted inhibition of epidermal growth factor receptor (EGFR) has represented a milestone in the treatment of lung cancer. Several studies convincingly and consistently demonstrated a significant superiority of EGFR-TKIs over standard platinum-chemotherapy in EGFR-mutated NSCLC patients, leading to the sequential approval of gefitinib, erlotinib and afatinib as new standard first-line clinical treatment. To date we are witnessing a second revolution in the management of EGFR-positive NSCLC thanks to the development of new treatment strategies aiming to overcome acquired resistance to TKIs and ultimately improve patients’ outcomes. In this review we summarize the most important recent findings regarding EGFR-inhibition in NSCLC, highlighting the current unsolved questions on the selection of the best TKI in first-line, which therapy can be combined with upfront EGFR-TKIs, how to overcome acquired resistance, and which are the clinical applications of liquid biopsy

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Risk of Treatment-Related Toxicities from EGFR Tyrosine Kinase Inhibitors: A Meta-analysis of Clinical Trials of Gefitinib, Erlotinib, and Afatinib in Advanced EGFR -Mutated Non–Small Cell Lung Cancer

Abstract: 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.

Cited by 132 publications

References 33 publications

Clinical analysis of EGFR‐positive non‐small cell lung cancer patients treated with first‐line afatinib: A Nagano Lung Cancer Research Group

Clinical analysis of EGFR‐positive non‐small cell lung cancer patients treated with first‐line afatinib: A Nagano Lung Cancer Research Group

The effects of switching EGFR‐TKI treatments for non‐small cell lung cancer because of adverse events

EGFR inhibition in NSCLC: New findings…. and opened questions?

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