Real-world multicentre experience of first-line afatinib in patients with EGFR-mutant advanced non-small cell lung cancer
Background : Afatinib is an irreversible, second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) that has been shown to be more potent than platinum doublet chemotherapy as well as the firstgeneration EGFR-TKI in patients with EGFR-mutant advanced non-small cell lu...
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my.iium.irep.862312021-04-20T04:08:30Z http://irep.iium.edu.my/86231/ Real-world multicentre experience of first-line afatinib in patients with EGFR-mutant advanced non-small cell lung cancer Liam, Chong Kin Chai, Chee Shee Ho, Gwo Fuang Alip, Adlinda Abdul Wahid, Mohd Ibrahim Abdullah, Matin Melor Foo, Yoke Ching How, Soon Hin Zaatar, Adel Lam, Kai Seng Leong, Kin Wah Seng Hoi, John Low Md Yusof, Mastura R Medicine (General) RC731 Specialties of Internal Medicine-Diseases of The Respiratory System Background : Afatinib is an irreversible, second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) that has been shown to be more potent than platinum doublet chemotherapy as well as the firstgeneration EGFR-TKI in patients with EGFR-mutant advanced non-small cell lung cancer (NSCLC). This study aimed to evaluate the efficacy, side-effects and resistance mechanisms of first-line afatinib in a real-world setting. Method : This is a multicentre observational study of Malaysian patients with EGFR-mutant advanced NSCLC started on first-line afatinib from 1st October 2014 to 30th April 2018. Results : The demographic and clinical characteristics of 85 patients who met the study criteria are shown in Table 1. EGFR mutations harboured by the tumours included exon 19 deletion in 80.0%, exon 21 L858R point mutation in 12.9%, and rare or complex EGFR mutations in 7.1%. Of the patients. 18.8% of the patients had an ECOG performance status of 2-4, 29.4% had baseline symptomatic brain metastases and 17.6% had abnormal organ function. Table 2 shows the starting dose, dose adjustment and optimal dose of afatinib. Afatinib 40 mg or 30 mg once daily were the most common starting and maintenance doses. Treatment outcome (Tables 3, 4 and 5; Figures 1 and 2) Response to afatinib The objective response rate (ORR) was 76.5% while the disease control rate (DCR) was 95.3% on first-line afatinib (Table 3). Two (2.4%) patients had complete response. Patients without baseline brain metastases had a significantly higher ORR than those with baseline brain metastases (Table 4). There was a trend for patients in whom the dose of afatinib was reduced to experience higher ORR than those without dose adjustment. On multivariate subgroup analyses involving covariates shown in Table 4, patients without symptomatic brain metastases had significantly higher ORR than that of those with symptomatic brain metastases (81.7% versus 56.0%; OR, 4.51; 95% CI, 1.45–14.00; p = 0.009); while patients with afatinib dose reduction had significantly higher ORR than that of those without dose adjustment (88.5% versus 65.3%; OR, 5.53; 95% CI, 1.32–23.24; p = 0.019). Progression-free survival 56 (65.9%) patients had PD at the time of analysis with a mPFS of 14.2 (95% CI, 11.85 – 16.55) months (Figure 1) Conclusion : Afatinib is an effective first-line treatment for patients with EGFR-mutant advanced NSCLC with good response and disease control rates as well as long PFS even in patients with unfavourable clinical characteristics. The side-effects of afatinib were manageable and acquired T790M mutation was the acquired resistance mechanism in 42% of patients with PD who underwent rebiopsy 2019-09-09 Conference or Workshop Item PeerReviewed application/pdf en http://irep.iium.edu.my/86231/1/WCLC2019%20poster_Real%20World%20Multicenter%20Experience%20of%20First-line%20Afatinib_25Aug2019.pdf application/pdf en http://irep.iium.edu.my/86231/7/WCLC2019-Abstract-Book_web-friendly.pdf Liam, Chong Kin and Chai, Chee Shee and Ho, Gwo Fuang and Alip, Adlinda and Abdul Wahid, Mohd Ibrahim and Abdullah, Matin Melor and Foo, Yoke Ching and How, Soon Hin and Zaatar, Adel and Lam, Kai Seng and Leong, Kin Wah and Seng Hoi, John Low and Md Yusof, Mastura (2019) Real-world multicentre experience of first-line afatinib in patients with EGFR-mutant advanced non-small cell lung cancer. In: IASLC World Conference on Lung Cancer 2019, 7-10 September 2019, Barcelona, Spain. (Unpublished) |
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R Medicine (General) RC731 Specialties of Internal Medicine-Diseases of The Respiratory System Liam, Chong Kin Chai, Chee Shee Ho, Gwo Fuang Alip, Adlinda Abdul Wahid, Mohd Ibrahim Abdullah, Matin Melor Foo, Yoke Ching How, Soon Hin Zaatar, Adel Lam, Kai Seng Leong, Kin Wah Seng Hoi, John Low Md Yusof, Mastura Real-world multicentre experience of first-line afatinib in patients with EGFR-mutant advanced non-small cell lung cancer |
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Background : Afatinib is an irreversible, second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) that has been shown to be more potent than platinum doublet chemotherapy as well as the firstgeneration EGFR-TKI in patients with EGFR-mutant advanced non-small cell lung cancer (NSCLC). This study aimed to evaluate the efficacy, side-effects and resistance mechanisms of first-line afatinib in a real-world setting.
Method : This is a multicentre observational study of Malaysian patients with EGFR-mutant advanced NSCLC started on first-line afatinib from 1st October 2014 to 30th April 2018.
Results : The demographic and clinical characteristics of 85 patients who met the study criteria are shown in Table 1. EGFR mutations harboured by the tumours included exon 19 deletion in 80.0%, exon 21 L858R point mutation in 12.9%, and rare or complex EGFR mutations in 7.1%. Of the patients. 18.8% of the patients had an ECOG performance status of 2-4, 29.4% had baseline symptomatic brain metastases and 17.6% had abnormal organ function. Table 2 shows the starting dose, dose adjustment and optimal dose of afatinib. Afatinib 40 mg or 30 mg once daily were the most common starting and maintenance doses. Treatment outcome (Tables 3, 4 and 5; Figures 1 and 2) Response to afatinib The objective response rate (ORR) was 76.5% while the disease control rate (DCR) was 95.3% on first-line afatinib (Table 3). Two (2.4%) patients had complete response. Patients without baseline brain metastases had a significantly higher ORR than those with baseline brain metastases (Table 4). There was a trend for patients in whom the dose of afatinib was reduced to experience higher ORR than those without dose adjustment. On multivariate subgroup analyses involving covariates shown in Table 4, patients without symptomatic brain metastases had significantly higher ORR than that of those with symptomatic brain metastases (81.7% versus 56.0%; OR, 4.51; 95% CI, 1.45–14.00; p = 0.009); while patients with afatinib dose reduction had significantly higher ORR than that of those without dose adjustment (88.5% versus 65.3%; OR, 5.53; 95% CI, 1.32–23.24; p = 0.019). Progression-free survival 56 (65.9%) patients had PD at the time of analysis with a mPFS of 14.2 (95% CI, 11.85 – 16.55) months (Figure 1)
Conclusion : Afatinib is an effective first-line treatment for patients with EGFR-mutant advanced NSCLC with good response and disease control rates as well as long PFS even in patients with unfavourable clinical characteristics. The side-effects of afatinib were manageable and acquired T790M mutation was the acquired resistance mechanism in 42% of patients with PD who underwent rebiopsy |
format |
Conference or Workshop Item |
author |
Liam, Chong Kin Chai, Chee Shee Ho, Gwo Fuang Alip, Adlinda Abdul Wahid, Mohd Ibrahim Abdullah, Matin Melor Foo, Yoke Ching How, Soon Hin Zaatar, Adel Lam, Kai Seng Leong, Kin Wah Seng Hoi, John Low Md Yusof, Mastura |
author_facet |
Liam, Chong Kin Chai, Chee Shee Ho, Gwo Fuang Alip, Adlinda Abdul Wahid, Mohd Ibrahim Abdullah, Matin Melor Foo, Yoke Ching How, Soon Hin Zaatar, Adel Lam, Kai Seng Leong, Kin Wah Seng Hoi, John Low Md Yusof, Mastura |
author_sort |
Liam, Chong Kin |
title |
Real-world multicentre experience of first-line afatinib in patients with EGFR-mutant advanced non-small cell lung cancer |
title_short |
Real-world multicentre experience of first-line afatinib in patients with EGFR-mutant advanced non-small cell lung cancer |
title_full |
Real-world multicentre experience of first-line afatinib in patients with EGFR-mutant advanced non-small cell lung cancer |
title_fullStr |
Real-world multicentre experience of first-line afatinib in patients with EGFR-mutant advanced non-small cell lung cancer |
title_full_unstemmed |
Real-world multicentre experience of first-line afatinib in patients with EGFR-mutant advanced non-small cell lung cancer |
title_sort |
real-world multicentre experience of first-line afatinib in patients with egfr-mutant advanced non-small cell lung cancer |
publishDate |
2019 |
url |
http://irep.iium.edu.my/86231/1/WCLC2019%20poster_Real%20World%20Multicenter%20Experience%20of%20First-line%20Afatinib_25Aug2019.pdf http://irep.iium.edu.my/86231/7/WCLC2019-Abstract-Book_web-friendly.pdf http://irep.iium.edu.my/86231/ |
_version_ |
1698696740306157568 |
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13.160551 |