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74: Tyrosine kinase inhibitors: Maintaining dose intensity with prophylactic antibiotic
Poster abstracts of the 15th Annual BTOG / Lung Cancer 103S1 (2017) S1–S81
73
Tyrosine kinase inhibitors (TKIs) as first-line treatment for advanced EGFR mutated non-small cell lung cancer (NSCLC): a single-centre experience
H. Buckley1, A. Ralph2, H. Liu3, D. Gilligan1, S. Harden1 Department Of Oncology, Cambridge University Hospital NHS Foundation Trust, Cambridge, United Kingdom; 2School Of Medicine, University of Cardiff, Cardiff, United Kingdom; 3Molecular Malignancy Laboratory, Haematology And Oncology Diagnostic Service, Cambridge University Hospital NHS Foundation Trust, Cambridge, United Kingdom
1
74
Tyrosine kinase inhibitors: Maintaining dose intensity with prophylactic antibiotic
C.S. Barrie, M. Mackean, T. Evans, F. Little, A. Price, S. Campbell, D. Borthwick, J. Mencnarowski Edinburgh Cancer Centre, NHS Lothian, Edinburgh, United Kingdom Introduction: Epidermal Growth Factor Receptor is overexpressed in Non-Small Cell Lung Cancer (NSCLC) and acts as an oncogenic driver (1). Physiologically it stimulates epidermal growth, inhibition of differentiation, and promotion of healing (2). Inhibition of EGFR results in an inflammatory response (2). Tyrosine Kinase Inhibitors (TKI) are known to induce a skin related toxicity, which can have an impact on patient’s quality of life and subsequent compliance (3). Reduced compliance and reduced dose intensity is likely to result in reduced efficacy of TKI’s (3). Based on the Pan Canadian Rash trial data, Edinburgh Cancer Centre adopted a prophylactic antibiotic use policy with TKI’s (4). The purpose of this audit is to quantify the effect this policy has had on the number of patients requiring a dose reduction. Methods: 136 patients identified as having an EGFR/ALK rearrangement mutation between October 2010-July 2016. Two Cohorts identified: 2010–2014 and 2015–2016 based upon the change in departmental policy on the use of prophylactic antibiotic. Number of patients commencing TKI treatment per year calculated, in addition to the number of patients requiring dose reduction. Number of patients commencing prophylactic antibiotic in each cohort collected. 30
Introduction of skin regime
Introduction: We report the outcome of EGFR-TKIs as the first-line treatment for advanced EGFR mutation-positive NSCLC. Methods: A retrospective analysis of patients who had EGFR mutation testing between July 2011-March 2015 at Addenbrooke’s Hospital was carried out. Results: 593 patients with NSCLC had EGFR mutation testing and 60 (10.1%) had an EGFR mutation. Complete follow-up data were available for 57 patients positive for EGFR mutation. The commonest mutations were exon 19 deletions (46%) and exon 21 mutations (36%). 15 patients had early stage disease at presentation (I-IIIa), 13 of whom progressed after initial radical treatment. On progression 9 patients received first-line TKI (gefitinib 7, erlotinib 1, afatanib 1) and 4 patients were managed symptomatically. 42 patients had advanced disease (IIIb-IV) at presentation. 32 received first-line TKI (27 gefitinib, 4 afatinib, 1 erlotinib), 4 patients initially received chemotherapy (3/4 switched onto TKI) and 6 patients were managed symptomatically. One stage IIIb patient had such an excellent downstaging response to gefitinib, they proceeded on to curative surgery. In total 44/55 (80%) patients with advanced disease received TKI. With a median follow up of 20.2 months, progressionfree survival (PFS) was 10.0 months (95% CI 8.0–24.4) and overall survival (OS) was 20.2 months (95% CI 16.7–32.8). There was no difference in PFS (p=0.67) and OS (p=0.62) from the start of TKI between patients progressing after initial radical treatment and patients presenting with advanced disease. Although the median PFS was longer in patients with exon 19 deletions (n=26) than exon 21 mutations (n=20), (19.3 vs. 7.0 months, p=0.023), there was no statistical difference in the median OS (20.2 vs. 5.7 months, p=0.09). Conclusion: The clinical outcomes for EGFR mutated NSCLC patients receiving first-line EGFR-TKI is similar to that of the IPASS trial. Patients with exon 19 deletions had a better PFS compared with those with exon 21 mutations. Disclosure: D. Gilligan: Speaker fees/honoraria/support to attend conferences received from Astra Zeneca, Boehringer Ingleheim and Roche. All other authors have declared no conflicts of interest.
Number of patients
25
60 50 40
20 15
30
27
20
10 15
14
13
5
10
10
% Requiring dose reduction
Guy’s Hospital. A mixture of rare mutations and deletions were identified. The age range for these 14 uncommon EGFR mutation patients was 48–85 (median 66.5). One patient was performance status(PS) 0, 12 patients (86%) PS 1 and one patient PS 2. First line gefitinib was used in 5 patients (36%), first line afatinib in 6 patients (43%), and second line erlotinib in 3 patients (21%). 9 patients (64%) responded to TKI treatment (partial response or stable disease), and 5 patients (36%) did not respond (progressive disease). Three of the five non-responders, were patients receiving erlotinib. Conclusion: A considerable number of NSCLC patients with uncommon EGFR mutations responded to first line TKI therapy. In our small study group, it was not possible to associate specific uncommon EGFR mutations with specific outcomes. Further research is required to better understand uncommon EGFR mutations, guiding therapy choices in these patients. Reference: [1] B Klughammer et al, Journal Thoracic Oncology April 2016. Disclosure: All authors have declared no conflicts of interest.
S35
0
0 2012
2013
2014
Total number starting TKI
2015
2016
% Requiring DR
Fig. 1 (abstract 74). Number of patients (EGFR mutation) starting TKI and the percentage requiring dose reduction year on year for skin toxicity.
Results: 2010–2014 cohort: 6/56 (11%) of patients had prophylactic antibiotic. 2015–2016 cohort: 23/23 (100%) of patients had prophylactic antibiotic. 2010–2015 cohort: 23/56 (41%) required a dose reduction for skin toxicity. 2015–2016 cohort: 3/23 (13%) required a dose reduction for skin toxicity. Chi-Square test between cohort and dose reduction is statistically significant at p=0.01. Conclusion: The introduction of prophylactic antibiotic has seen the number of patients requiring a dose reduction for skin toxicity reduce by approximately two-thirds (41–13%, p<0.05). This reduction in numbers has allowed clinicians to maintain maximum dose intensity in patients. Disclosure: All authors have declared no conflicts of interest.
75
EGFR-mutant non-small cell lung cancer in Aberdeen, Scotland – Treatment and outcomes
K. El-Shakankery1, E. Steven2, C. Clark3, C. Stilwell2, K. Kerr1, M. Nicolson2 1 School Of Medicine, University of Aberdeen, Aberdeen, United Kingdom; 2Department Of Oncology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom; 3Medical Genetics, Aberdeen Royal Infirmary, Aberdeen, United Kingdom
73
Tyrosine kinase inhibitors (TKIs) as first-line treatment for advanced EGFR mutated non-small cell lung cancer (NSCLC): a single-centre experience
H. Buckley1, A. Ralph2, H. Liu3, D. Gilligan1, S. Harden1 Department Of Oncology, Cambridge University Hospital NHS Foundation Trust, Cambridge, United Kingdom; 2School Of Medicine, University of Cardiff, Cardiff, United Kingdom; 3Molecular Malignancy Laboratory, Haematology And Oncology Diagnostic Service, Cambridge University Hospital NHS Foundation Trust, Cambridge, United Kingdom
1
74
Tyrosine kinase inhibitors: Maintaining dose intensity with prophylactic antibiotic
C.S. Barrie, M. Mackean, T. Evans, F. Little, A. Price, S. Campbell, D. Borthwick, J. Mencnarowski Edinburgh Cancer Centre, NHS Lothian, Edinburgh, United Kingdom Introduction: Epidermal Growth Factor Receptor is overexpressed in Non-Small Cell Lung Cancer (NSCLC) and acts as an oncogenic driver (1). Physiologically it stimulates epidermal growth, inhibition of differentiation, and promotion of healing (2). Inhibition of EGFR results in an inflammatory response (2). Tyrosine Kinase Inhibitors (TKI) are known to induce a skin related toxicity, which can have an impact on patient’s quality of life and subsequent compliance (3). Reduced compliance and reduced dose intensity is likely to result in reduced efficacy of TKI’s (3). Based on the Pan Canadian Rash trial data, Edinburgh Cancer Centre adopted a prophylactic antibiotic use policy with TKI’s (4). The purpose of this audit is to quantify the effect this policy has had on the number of patients requiring a dose reduction. Methods: 136 patients identified as having an EGFR/ALK rearrangement mutation between October 2010-July 2016. Two Cohorts identified: 2010–2014 and 2015–2016 based upon the change in departmental policy on the use of prophylactic antibiotic. Number of patients commencing TKI treatment per year calculated, in addition to the number of patients requiring dose reduction. Number of patients commencing prophylactic antibiotic in each cohort collected. 30
Introduction of skin regime
Introduction: We report the outcome of EGFR-TKIs as the first-line treatment for advanced EGFR mutation-positive NSCLC. Methods: A retrospective analysis of patients who had EGFR mutation testing between July 2011-March 2015 at Addenbrooke’s Hospital was carried out. Results: 593 patients with NSCLC had EGFR mutation testing and 60 (10.1%) had an EGFR mutation. Complete follow-up data were available for 57 patients positive for EGFR mutation. The commonest mutations were exon 19 deletions (46%) and exon 21 mutations (36%). 15 patients had early stage disease at presentation (I-IIIa), 13 of whom progressed after initial radical treatment. On progression 9 patients received first-line TKI (gefitinib 7, erlotinib 1, afatanib 1) and 4 patients were managed symptomatically. 42 patients had advanced disease (IIIb-IV) at presentation. 32 received first-line TKI (27 gefitinib, 4 afatinib, 1 erlotinib), 4 patients initially received chemotherapy (3/4 switched onto TKI) and 6 patients were managed symptomatically. One stage IIIb patient had such an excellent downstaging response to gefitinib, they proceeded on to curative surgery. In total 44/55 (80%) patients with advanced disease received TKI. With a median follow up of 20.2 months, progressionfree survival (PFS) was 10.0 months (95% CI 8.0–24.4) and overall survival (OS) was 20.2 months (95% CI 16.7–32.8). There was no difference in PFS (p=0.67) and OS (p=0.62) from the start of TKI between patients progressing after initial radical treatment and patients presenting with advanced disease. Although the median PFS was longer in patients with exon 19 deletions (n=26) than exon 21 mutations (n=20), (19.3 vs. 7.0 months, p=0.023), there was no statistical difference in the median OS (20.2 vs. 5.7 months, p=0.09). Conclusion: The clinical outcomes for EGFR mutated NSCLC patients receiving first-line EGFR-TKI is similar to that of the IPASS trial. Patients with exon 19 deletions had a better PFS compared with those with exon 21 mutations. Disclosure: D. Gilligan: Speaker fees/honoraria/support to attend conferences received from Astra Zeneca, Boehringer Ingleheim and Roche. All other authors have declared no conflicts of interest.
Number of patients
25
60 50 40
20 15
30
27
20
10 15
14
13
5
10
10
% Requiring dose reduction
Guy’s Hospital. A mixture of rare mutations and deletions were identified. The age range for these 14 uncommon EGFR mutation patients was 48–85 (median 66.5). One patient was performance status(PS) 0, 12 patients (86%) PS 1 and one patient PS 2. First line gefitinib was used in 5 patients (36%), first line afatinib in 6 patients (43%), and second line erlotinib in 3 patients (21%). 9 patients (64%) responded to TKI treatment (partial response or stable disease), and 5 patients (36%) did not respond (progressive disease). Three of the five non-responders, were patients receiving erlotinib. Conclusion: A considerable number of NSCLC patients with uncommon EGFR mutations responded to first line TKI therapy. In our small study group, it was not possible to associate specific uncommon EGFR mutations with specific outcomes. Further research is required to better understand uncommon EGFR mutations, guiding therapy choices in these patients. Reference: [1] B Klughammer et al, Journal Thoracic Oncology April 2016. Disclosure: All authors have declared no conflicts of interest.
S35
0
0 2012
2013
2014
Total number starting TKI
2015
2016
% Requiring DR
Fig. 1 (abstract 74). Number of patients (EGFR mutation) starting TKI and the percentage requiring dose reduction year on year for skin toxicity.
Results: 2010–2014 cohort: 6/56 (11%) of patients had prophylactic antibiotic. 2015–2016 cohort: 23/23 (100%) of patients had prophylactic antibiotic. 2010–2015 cohort: 23/56 (41%) required a dose reduction for skin toxicity. 2015–2016 cohort: 3/23 (13%) required a dose reduction for skin toxicity. Chi-Square test between cohort and dose reduction is statistically significant at p=0.01. Conclusion: The introduction of prophylactic antibiotic has seen the number of patients requiring a dose reduction for skin toxicity reduce by approximately two-thirds (41–13%, p<0.05). This reduction in numbers has allowed clinicians to maintain maximum dose intensity in patients. Disclosure: All authors have declared no conflicts of interest.
75
EGFR-mutant non-small cell lung cancer in Aberdeen, Scotland – Treatment and outcomes
K. El-Shakankery1, E. Steven2, C. Clark3, C. Stilwell2, K. Kerr1, M. Nicolson2 1 School Of Medicine, University of Aberdeen, Aberdeen, United Kingdom; 2Department Of Oncology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom; 3Medical Genetics, Aberdeen Royal Infirmary, Aberdeen, United Kingdom