- Email: [email protected]
Utilization and Treatment Patterns Among Patients with Advanced Non-Small Cell Lung Cancer Receiving Predictive Molecular Biomarker (BMX) Tests
A400
VA L U E I N H E A LT H 2 0 ( 2 0 1 7 ) A 3 9 9 – A 8 1 1
BREAKOUT SESSION II
P2: CANCER STUDIES CN1 Use of New Therapies and Hospital Admission Near the End of Life in Castration Resistant Prostate Cancer (CRPC) in the Castration Resistant Prostate Cancer Registry (CAPRI) in the Netherlands Kuppen M1, Westgeest H1, Van den Eertwegh A2, Gerritsen W3, Uyl - de Groot C1 1Erasmus University Rotterdam, Rotterdam, The Netherlands, 2VU University Medical Centre, Amsterdam, The Netherlands, 3Radboud University Medical Center, Nijmegen, The Netherlands
Objectives: Despite the availability of new therapies for CRPC, the disease remains incurable. The start of expensive treatments in the last three months before death is controversial, since toxicity often outweighs clinical benefit at high costs. The purpose of this study is to investigate the use of new therapeutic drugs and hospital admissions in the last three months before death. Methods: CAPRI is an observational, retrospective study in 20 hospitals in the Netherlands. Patients with a known date of death before March 1st, 2015 were included for this analysis. Results: 965 of all 1,524 CRPC patients diagnosed between 2010 and 2013 were included in this analysis. Hospital admission in the months before death increased from 28.5% of patients in six to three months before death, to 55.4% in the last three months before death (p< 0.001). Admission duration differed significantly (median 7 vs 12 days). In 11.1% of patients abiraterone, enzalutamide, cabazitaxel, or radium-223 was started in the last three months before death. Patients who started any new systemic treatment were younger (median 74 years vs 78 years), had better clinical performance scores (WHO 0-1 in 30.5% vs 16.9%), and more visceral metastases (31.0% vs 24.4%), compared to untreated patients. These patients had significantly higher admissions rates than untreated patients (75.1% vs 44.8%, p< 0.001) with a longer admission duration (median 14 days vs 10 days, p< 0.001). Conclusions: Admission rate and duration in CRPC-patients in the last 3 months of life was higher in patients who started new systemic treatment. These patients were younger and in better condition, and may have had a higher need for treatment. However, this group is a minority of the CRPC population, indicating adequate assessment of life expectancy and a tendency to best supportive care in the last 3 months of life in the Netherlands.
CN2 The Greta Study: Generating Real-World Evidence about Bevacizumab Treatment of Metastatic Colorectal Cancer by Linking Cancer Registries and Healthcare Databases in Italy Franchi M1, Caputo A2, Barni S3, De Ceglie MC4, Mazzucco W5, Ricci P6, Tagliabue G7, Tumino R8, Corrao G9 1University of Milano-Bicocca, Milano, Italy, 2Roche S.p.A., Monza, Italy, 3ASST Bergamo Ovest Ospedale di Treviglio, Treviglio, Italy, 4Roche S.p.A, Monza, Italy, 5University of Palermo, Palermo, Italy, 6Health Protection Agency Mantua&Cremona, NHS Italy, Mantova, Italy, 7Fondazione IRCCS National Cancer Institute, Milano, Italy, 8Provincial Health Authority, ASP Ragusa, Ragusa, Italy, 9Università di Milano-Bicocca, Milan, Italy
Objectives: Based on the results of randomized clinical trials, bevacizumab plus chemotherapy is currently recommended as first-line treatment for metastatic colorectal cancer (mCRC). However, scant real-world data are available about effectiveness of bevacizumab-containing therapy used in patients with mCRC in Italy. The GRETA observational cohort study was designed for comparing overall survival (OS) of mCRC patients treated with first-line bevacizumab plus chemotherapy (B+CT), as compared to CT alone, in the real-world setting of Italian clinical practice, by linking cancer registries and healthcare utilization (HCU) databases. Methods: Incident mCRC patients were identified during the period 2010-2012 from five populationbased cancer registries, representing the 5.4% of the entire Italian population. Cases were linked to Regional HCU databases, in order to obtain the entire pathway of health services provided to each patient. Patients who started a first-line treatment with either B+CT or CT alone were included in the study cohort. A propensity score (PS) method was applied in order to take into account residual confounding. Results: A study cohort of 480 subjects was selected, of which 101 received first-line B+CT and 379 CT alone. The median OS was 22.5 and 14.6 months in patients treated with or without bevacizumab, respectively (p= 0.011). The corresponding adjusted hazard ratio (HR) was 0.82 (95% CI 0.62-1.08). The HR resulting from the PS matched analysis was 0.86 (95% CI 0.56-1.33). The gain in median OS was 8.3 months among patients aged less than 70 years (p= 0.087) and 4.3 months among those aged 70 years or older (p= 0.221). Conclusions: Despite not statistically significant, the addition of bevacizumab to CT showed a beneficial effect on OS, in the real-world clinical practice of mCRC patients in Italy. The gain in OS is comparable to that from the pivotal trial. CN3 Assessing the Consistency in Reporting of Adverse Events Across Data Sources for Multiple Myeloma Treatment Kish J1, Feinberg B2 1Cardinal Health Specialty Solutions, Dallas, TX, USA, 2Cardinal Health, Dublin, OH, USA
Objectives: There can be significant variability in the representation (all grades vs grade 3/4), reporting (≥ 5 vs ≥ 10% of the study population) and even frequency of adverse events (AEs) across peer-reviewed manuscripts and the package inserts (PIs) of pharmaceutical products. We aimed to collate rates of all reported AEs for multiple myeloma (MM) treatments to assess consistency in reporting. Methods: Manuscripts for registrational trials and PIs for MM therapies were reviewed including for all approved proteasome inhibitors and immunomodulatory drugs, monoclonal antibodies, and select chemotherapies. All adverse events (AEs) in Section 5, 6 and 14 of the PI and all events reported in manuscripts were abstracted. Rates of events
by grades were abstracted (or calculated) to assess variability. Results: 119 distinct AEs were reported across 10 products. Events occurring in > 30% of patients included: anemia, diarrhea, fatigue, leukopenia lymphopenia, neutropenia, pneumonia and thrombocytopenia. 41 events were found occurring in > 5% of the population. Nearly 50% (19/41) events had rates reported differently between the trial and PI with 12/19 differences in pomalidomide materials. For example, grade 3/4 pneumonia was reported in 19.6% and 28.6% of patients, respectively in the trial publication versus PI. A small but potentially clinically meaningful difference in the rate of cardiac failure was noted for cafilizomib (6.4% trial publication v 6.0% PI). Other differences, such as 17.0% v 9.3% were noted in the pomalidomide trial publication v PI for asthenia and fatigue. Conclusions: There is heterogeneity in both the criteria used and the rates reported for common and serious AEs related to MM treatment across and within published materials. Meta-analysis, budget impact models, and value calculators utilize these data, often with vague references to sources. Source material used should be clarified and investigation of these findings should be confirmed in other tumor types. CN4 Utilization and Treatment Patterns Among Patients with Advanced Non-Small Cell Lung Cancer Receiving Predictive Molecular Biomarker (BMX) Tests Kothari S1, Arunachalam A2, Tsao M3, Lee DH4, Kambartel K5, Isobe H6, Huang M7, Escosteguy Barrios CH8, Khattak A9, de Marinis F10, Cao X11, Burke T12, Lopez MA13, De Castro J14 1Merck & Co, Kenilworth, NJ, USA, 2Merck & Co., Inc., North Wales, PA, USA, 3University Health Network, Princess Margaret Cancer Centre, Toronto, ON, Canada, 4Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Korea, Republic of (South), 5Bethanien Hospital, Moers, Germany, 6KKR Sapporo Medical Center, Sapporo, Japan, 7Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan, 8PUCRS School of Medicine, Porto Alegre, Brazil, 9FIona Stanley Hospital, Murdoch, Australia, 10European Institute of Oncology, Milan, Italy, 11Merck & Co, Inc, Kenilworth, NJ, USA, 12Merck & Co., Inc., Lebanon, NJ, USA, 13MSD, Madrid, Spain, 14Hospital Universitario La Paz, MADRID, Spain
Objectives: This study characterized Bmx testing, treatment patterns and overall survival (OS) among advanced NSCLC patients. Methods: This chart review study, conducted in Italy, Spain, Germany, Australia, Japan, Korea, Taiwan, and Brazil, included 1440 newly diagnosed NSCLC patients (stage IIIB/IV) initiating systemic therapy from 01/Jan/2011-01/July/2013, with follow-up until July-2016. Treatment patterns and survival were evaluated by histology, line of therapy and receipt of a Bmx test (EGFR mutation (EGFR-m)/ ALK rearrangements (ALK-r) ever (yes/no) & by mutation status for tested patients (EGFR-m/ALK-r positive/EGFR-m/ALK-r negative/unknown). Country specific data were analyzed descriptively and presented as ranges (lowest – highest country). Overall survival (OS) from start of first line (1L) was estimated using Kaplan Meier method. Results: Overall, patients with ≥ 1 Bmx test varied from 43% (Brazil) - 85% (Taiwan). Numerically, mostly females with stage-IV non-squamous NSCLC (NSQ), Asians, never/former-smokers received a test. Testing was common in NSQ (54% (Brazil)-91% (Taiwan)). Among NSQ patients, the percentages of positive EGFR-m and ALK-r tests ranged from 17% (Brazil)–67% (Taiwan) and 0% (Brazil)-60% (Taiwan) respectively. NSQ patients with positive EGFR-m/ ALK-r status receiving a 1L targeted therapy ranged from 30% (Germany) to 89% (Japan). Platinum-based combinations (PBC) were used as 1LT for 88% (Japan) to 98% (Brazil) NSQ tested patients with negative/inconclusive test results. Among untested patients, majority in 1L received PBC 80% (Italy) - 98% (Spain) except in Taiwan, where 41% received single agents. Median OS from start of 1L ranged from 10 (Japan) to 26.7 (Taiwan) months for tested and 7.6 (Australia/Brazil) to 19.3 (Taiwan) months for untested patients. Conclusions: Results suggests that patients with advanced NSCLC were commonly tested for molecular biomarkers at the time of the study and received targeted therapy according to their mutation status. Survival outcomes of patients receiving targeted therapy were comparable to published literature.
BREAKOUTS SESSION III
P3: STUDIES ON HEALTH TECHNOLOGY ASSESSMENT AGENCIES HT1 Playing in the Same Pond - The Impact of Brexit on Clinical Trials and Access Wang GD, Macaulay R PAREXEL International, London, UK
Objectives: Patient access to potentially life-saving treatments through clinical trials (CTs) is at risk due to Brexit (March 2019). Currently, all CTs conducted in the UK require approval by the MHRA in line with EU Directive 2001/20/EC, which will be replaced by EU Regulation 536/2014 in 2019. This research aims to examine the impact on patient access to pioneering and innovative therapies through CTs in the UK. Methods: Publically available ABPI, clinicaltrials.gov, EFPIA, EMA, EudraCT, MHRA and NIHR data were screened up to 16/06/2017 for key information including the number of CTs involving the UK and EU Member States (MSs). Results: Approximately 4,000 CTs are conducted annually in the EEA, each involving on average 2 MSs. The UK is the second-ranked MS in terms of number of commercially sponsored CTs (85/year, 2010-2015) behind only Germany (90/year). Application of the new regulation will impact the number of the pan-European CTs with the UK as a MS (currently 6,585 ongoing CTs out of 30,506 in the EU). Approximately 605,000 individuals were involved in CTs in the UK in 2015/6, including 35,000 in commercially-sponsored CTs. A substantial number of those will have been enrolled in phase II/III trials - in 2015, 622/842 UK commercial CTs applications were for phase II/III trials, with only Germany having more phase II/III trials. Conclusions: Brexit could potentially deny thousands of UK patients the access to pioneering and innovative candidate treatments as UK trial sites will no longer need to align to EU CT regulations. Consequentially, results of CTs conducted outside the UK will be
VA L U E I N H E A LT H 2 0 ( 2 0 1 7 ) A 3 9 9 – A 8 1 1
BREAKOUT SESSION II
P2: CANCER STUDIES CN1 Use of New Therapies and Hospital Admission Near the End of Life in Castration Resistant Prostate Cancer (CRPC) in the Castration Resistant Prostate Cancer Registry (CAPRI) in the Netherlands Kuppen M1, Westgeest H1, Van den Eertwegh A2, Gerritsen W3, Uyl - de Groot C1 1Erasmus University Rotterdam, Rotterdam, The Netherlands, 2VU University Medical Centre, Amsterdam, The Netherlands, 3Radboud University Medical Center, Nijmegen, The Netherlands
Objectives: Despite the availability of new therapies for CRPC, the disease remains incurable. The start of expensive treatments in the last three months before death is controversial, since toxicity often outweighs clinical benefit at high costs. The purpose of this study is to investigate the use of new therapeutic drugs and hospital admissions in the last three months before death. Methods: CAPRI is an observational, retrospective study in 20 hospitals in the Netherlands. Patients with a known date of death before March 1st, 2015 were included for this analysis. Results: 965 of all 1,524 CRPC patients diagnosed between 2010 and 2013 were included in this analysis. Hospital admission in the months before death increased from 28.5% of patients in six to three months before death, to 55.4% in the last three months before death (p< 0.001). Admission duration differed significantly (median 7 vs 12 days). In 11.1% of patients abiraterone, enzalutamide, cabazitaxel, or radium-223 was started in the last three months before death. Patients who started any new systemic treatment were younger (median 74 years vs 78 years), had better clinical performance scores (WHO 0-1 in 30.5% vs 16.9%), and more visceral metastases (31.0% vs 24.4%), compared to untreated patients. These patients had significantly higher admissions rates than untreated patients (75.1% vs 44.8%, p< 0.001) with a longer admission duration (median 14 days vs 10 days, p< 0.001). Conclusions: Admission rate and duration in CRPC-patients in the last 3 months of life was higher in patients who started new systemic treatment. These patients were younger and in better condition, and may have had a higher need for treatment. However, this group is a minority of the CRPC population, indicating adequate assessment of life expectancy and a tendency to best supportive care in the last 3 months of life in the Netherlands.
CN2 The Greta Study: Generating Real-World Evidence about Bevacizumab Treatment of Metastatic Colorectal Cancer by Linking Cancer Registries and Healthcare Databases in Italy Franchi M1, Caputo A2, Barni S3, De Ceglie MC4, Mazzucco W5, Ricci P6, Tagliabue G7, Tumino R8, Corrao G9 1University of Milano-Bicocca, Milano, Italy, 2Roche S.p.A., Monza, Italy, 3ASST Bergamo Ovest Ospedale di Treviglio, Treviglio, Italy, 4Roche S.p.A, Monza, Italy, 5University of Palermo, Palermo, Italy, 6Health Protection Agency Mantua&Cremona, NHS Italy, Mantova, Italy, 7Fondazione IRCCS National Cancer Institute, Milano, Italy, 8Provincial Health Authority, ASP Ragusa, Ragusa, Italy, 9Università di Milano-Bicocca, Milan, Italy
Objectives: Based on the results of randomized clinical trials, bevacizumab plus chemotherapy is currently recommended as first-line treatment for metastatic colorectal cancer (mCRC). However, scant real-world data are available about effectiveness of bevacizumab-containing therapy used in patients with mCRC in Italy. The GRETA observational cohort study was designed for comparing overall survival (OS) of mCRC patients treated with first-line bevacizumab plus chemotherapy (B+CT), as compared to CT alone, in the real-world setting of Italian clinical practice, by linking cancer registries and healthcare utilization (HCU) databases. Methods: Incident mCRC patients were identified during the period 2010-2012 from five populationbased cancer registries, representing the 5.4% of the entire Italian population. Cases were linked to Regional HCU databases, in order to obtain the entire pathway of health services provided to each patient. Patients who started a first-line treatment with either B+CT or CT alone were included in the study cohort. A propensity score (PS) method was applied in order to take into account residual confounding. Results: A study cohort of 480 subjects was selected, of which 101 received first-line B+CT and 379 CT alone. The median OS was 22.5 and 14.6 months in patients treated with or without bevacizumab, respectively (p= 0.011). The corresponding adjusted hazard ratio (HR) was 0.82 (95% CI 0.62-1.08). The HR resulting from the PS matched analysis was 0.86 (95% CI 0.56-1.33). The gain in median OS was 8.3 months among patients aged less than 70 years (p= 0.087) and 4.3 months among those aged 70 years or older (p= 0.221). Conclusions: Despite not statistically significant, the addition of bevacizumab to CT showed a beneficial effect on OS, in the real-world clinical practice of mCRC patients in Italy. The gain in OS is comparable to that from the pivotal trial. CN3 Assessing the Consistency in Reporting of Adverse Events Across Data Sources for Multiple Myeloma Treatment Kish J1, Feinberg B2 1Cardinal Health Specialty Solutions, Dallas, TX, USA, 2Cardinal Health, Dublin, OH, USA
Objectives: There can be significant variability in the representation (all grades vs grade 3/4), reporting (≥ 5 vs ≥ 10% of the study population) and even frequency of adverse events (AEs) across peer-reviewed manuscripts and the package inserts (PIs) of pharmaceutical products. We aimed to collate rates of all reported AEs for multiple myeloma (MM) treatments to assess consistency in reporting. Methods: Manuscripts for registrational trials and PIs for MM therapies were reviewed including for all approved proteasome inhibitors and immunomodulatory drugs, monoclonal antibodies, and select chemotherapies. All adverse events (AEs) in Section 5, 6 and 14 of the PI and all events reported in manuscripts were abstracted. Rates of events
by grades were abstracted (or calculated) to assess variability. Results: 119 distinct AEs were reported across 10 products. Events occurring in > 30% of patients included: anemia, diarrhea, fatigue, leukopenia lymphopenia, neutropenia, pneumonia and thrombocytopenia. 41 events were found occurring in > 5% of the population. Nearly 50% (19/41) events had rates reported differently between the trial and PI with 12/19 differences in pomalidomide materials. For example, grade 3/4 pneumonia was reported in 19.6% and 28.6% of patients, respectively in the trial publication versus PI. A small but potentially clinically meaningful difference in the rate of cardiac failure was noted for cafilizomib (6.4% trial publication v 6.0% PI). Other differences, such as 17.0% v 9.3% were noted in the pomalidomide trial publication v PI for asthenia and fatigue. Conclusions: There is heterogeneity in both the criteria used and the rates reported for common and serious AEs related to MM treatment across and within published materials. Meta-analysis, budget impact models, and value calculators utilize these data, often with vague references to sources. Source material used should be clarified and investigation of these findings should be confirmed in other tumor types. CN4 Utilization and Treatment Patterns Among Patients with Advanced Non-Small Cell Lung Cancer Receiving Predictive Molecular Biomarker (BMX) Tests Kothari S1, Arunachalam A2, Tsao M3, Lee DH4, Kambartel K5, Isobe H6, Huang M7, Escosteguy Barrios CH8, Khattak A9, de Marinis F10, Cao X11, Burke T12, Lopez MA13, De Castro J14 1Merck & Co, Kenilworth, NJ, USA, 2Merck & Co., Inc., North Wales, PA, USA, 3University Health Network, Princess Margaret Cancer Centre, Toronto, ON, Canada, 4Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Korea, Republic of (South), 5Bethanien Hospital, Moers, Germany, 6KKR Sapporo Medical Center, Sapporo, Japan, 7Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan, 8PUCRS School of Medicine, Porto Alegre, Brazil, 9FIona Stanley Hospital, Murdoch, Australia, 10European Institute of Oncology, Milan, Italy, 11Merck & Co, Inc, Kenilworth, NJ, USA, 12Merck & Co., Inc., Lebanon, NJ, USA, 13MSD, Madrid, Spain, 14Hospital Universitario La Paz, MADRID, Spain
Objectives: This study characterized Bmx testing, treatment patterns and overall survival (OS) among advanced NSCLC patients. Methods: This chart review study, conducted in Italy, Spain, Germany, Australia, Japan, Korea, Taiwan, and Brazil, included 1440 newly diagnosed NSCLC patients (stage IIIB/IV) initiating systemic therapy from 01/Jan/2011-01/July/2013, with follow-up until July-2016. Treatment patterns and survival were evaluated by histology, line of therapy and receipt of a Bmx test (EGFR mutation (EGFR-m)/ ALK rearrangements (ALK-r) ever (yes/no) & by mutation status for tested patients (EGFR-m/ALK-r positive/EGFR-m/ALK-r negative/unknown). Country specific data were analyzed descriptively and presented as ranges (lowest – highest country). Overall survival (OS) from start of first line (1L) was estimated using Kaplan Meier method. Results: Overall, patients with ≥ 1 Bmx test varied from 43% (Brazil) - 85% (Taiwan). Numerically, mostly females with stage-IV non-squamous NSCLC (NSQ), Asians, never/former-smokers received a test. Testing was common in NSQ (54% (Brazil)-91% (Taiwan)). Among NSQ patients, the percentages of positive EGFR-m and ALK-r tests ranged from 17% (Brazil)–67% (Taiwan) and 0% (Brazil)-60% (Taiwan) respectively. NSQ patients with positive EGFR-m/ ALK-r status receiving a 1L targeted therapy ranged from 30% (Germany) to 89% (Japan). Platinum-based combinations (PBC) were used as 1LT for 88% (Japan) to 98% (Brazil) NSQ tested patients with negative/inconclusive test results. Among untested patients, majority in 1L received PBC 80% (Italy) - 98% (Spain) except in Taiwan, where 41% received single agents. Median OS from start of 1L ranged from 10 (Japan) to 26.7 (Taiwan) months for tested and 7.6 (Australia/Brazil) to 19.3 (Taiwan) months for untested patients. Conclusions: Results suggests that patients with advanced NSCLC were commonly tested for molecular biomarkers at the time of the study and received targeted therapy according to their mutation status. Survival outcomes of patients receiving targeted therapy were comparable to published literature.
BREAKOUTS SESSION III
P3: STUDIES ON HEALTH TECHNOLOGY ASSESSMENT AGENCIES HT1 Playing in the Same Pond - The Impact of Brexit on Clinical Trials and Access Wang GD, Macaulay R PAREXEL International, London, UK
Objectives: Patient access to potentially life-saving treatments through clinical trials (CTs) is at risk due to Brexit (March 2019). Currently, all CTs conducted in the UK require approval by the MHRA in line with EU Directive 2001/20/EC, which will be replaced by EU Regulation 536/2014 in 2019. This research aims to examine the impact on patient access to pioneering and innovative therapies through CTs in the UK. Methods: Publically available ABPI, clinicaltrials.gov, EFPIA, EMA, EudraCT, MHRA and NIHR data were screened up to 16/06/2017 for key information including the number of CTs involving the UK and EU Member States (MSs). Results: Approximately 4,000 CTs are conducted annually in the EEA, each involving on average 2 MSs. The UK is the second-ranked MS in terms of number of commercially sponsored CTs (85/year, 2010-2015) behind only Germany (90/year). Application of the new regulation will impact the number of the pan-European CTs with the UK as a MS (currently 6,585 ongoing CTs out of 30,506 in the EU). Approximately 605,000 individuals were involved in CTs in the UK in 2015/6, including 35,000 in commercially-sponsored CTs. A substantial number of those will have been enrolled in phase II/III trials - in 2015, 622/842 UK commercial CTs applications were for phase II/III trials, with only Germany having more phase II/III trials. Conclusions: Brexit could potentially deny thousands of UK patients the access to pioneering and innovative candidate treatments as UK trial sites will no longer need to align to EU CT regulations. Consequentially, results of CTs conducted outside the UK will be