- Email: [email protected]
Switch maintenance gemcitabine after first-line chemotherapy in patients with malignant mesothelioma: A multicenter open label phase II trial (NVALT19)
THORACIC MALIGNANCIES, OTHER
S. Popat1, A. Curioni-Fontecedro2, V. Polydoropoulou3, R. Shah4, M. O’Brien5, A. Pope6, P. Fisher7, J. Spicer8, A. Roy9, D. Gilligan10, O. Gautschi11, E. Nadal12, W-D. Janthur13, R. L opez Castro14, R. Garcıa Campelo15, H. Roschitzki-Voser16, B. Ruepp16, S. Rusakiewicz17, S. Peters18, R.A. Stahel2 1 Medicine, Royal Marsden Hospital, London, UK, 2Center of Hematology and Oncology, University Hospital, Zurich, Switzerland, 3Statistics, Frontier Science Foundation-Hellas, Athens, Greece, 4Medical Oncology, Kent Oncology Centre, Maidstone, UK, 5Medicine, Royal Marsden Hospital Sutton, UK, 6Medical Oncology, Clatterbridge Cancer Centre, Liverpool, UK, 7Medical Oncology, Weston Park Hospital, Sheffield, UK, 8Comprehensive Cancer Centre, King’s College London Guy’s Hospital, London, UK, 9Medical Oncology, Plymouth Hospitals NHS Trust, Plymouth, UK, 10Medical Oncology, Addenbrooke’s Hospital, Cambridge, UK, 11Medical Oncology, Cantonal Hospital Luzern and Swiss Group for Clinical Cancer Research, Luzern, Switzerland, 12Catalan Institute of Oncology, L’Hospitalet Barcelona, Barcelona, Spain, 13Medical Oncology, Cantonal Hospital Aarau and Swiss Group for Clinical Cancer Research, Aarau, Switzerland, 14 Department of Oncology, Hospital Clınico Universitario de Valladolid, Valladolid, Spain, 15Medical Oncology, Hospital Teresa Herrera, La Coru~ na, Spain, 16Coordinating Office, European Thoracic Oncology Platform (ETOP), Bern, Switzerland, 17Centre of Experimental Therapies (CTE), Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland, 18Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland Background: MPM is an aggressive malignancy of increasing prevalence and poor prognosis. At relapse after platinum-based (pb) CT, single agent CT is commonly used and single arm trials of immune checkpoint inhibitors have demonstrated encouraging activity. Methods: PROMISE-meso is an open-label 1:1 randomized phase III trial investigating the efficacy of P (200 mg/Q3W) vs institutional choice single agent CT (gemcitabine or vinorelbine) in relapsed MPM patients (pts) failing one previous line of pb CT. Pts were of PS 0-1 and unselected for PD-L1 status. P beyond progression (PD) for clinical benefit and crossover to P at PD on CT were allowed. Primary endpoint was progression-free survival (PFS, RECIST 1.1) by independent radiological review (IR). The trial was designed to detect an increase in median PFS from 3.5 months (ms) to 6ms with P (HR ¼ 0.58, 80% power, 1-sided a ¼ 0.025). 142 pts were needed to observe the required 110 events. Secondary endpoints were overall survival (OS), investigator assessed (IA) PFS, objective response rate (ORR), adverse events (AE), while efficacy by PD-L1 status was exploratory. Results: Between 09/17 and 08/18, 144 pts were randomized, 73 to P and 71 to CT. At 20/02/19 data lock, 70 pts were on follow-up (median 12ms). Pts were of median age 70 years, 82% males, 77% poor EORTC prognostic score, 50% never smokers, 89% epithelioid histology and 65% (of 102 available) TPS1%. ORRs were 22% in P, 6% in CT (p ¼ 0.004). 62 IR PFS events were observed in P vs 56 in CT, median PFS 2.5ms (95%CI 2.1-4.2) vs 3.4ms (2.2-4.3), HR ¼ 1.06 (0.73–1.53), p ¼ 0.76. Median OS was 10.7ms for P vs 11.7ms for CT, HR ¼ 1.05 (0.66-1.67), p ¼ 0.85. 45 CT pts crossed over to P. Accounting for crossover yielded similar OS results. Treatment-related AEs grade 3 were experienced by 19% P vs 24% CT pts, one fatal per arm. Most common AEs were fatigue (19%) in P vs nausea (27%) and fatigue (31%) in CT. Conclusions: This is the first randomized trial evaluating the efficacy of P vs single agent CT in MPM pts progressing after or on previous pb CT. In unselected pts, whilst associated with an improved ORR, P does not improve PFS or OS over single agent CT. Clinical trial identification: NCT02991482. Legal entity responsible for the study: European Thoracic Oncology Platform (ETOP). Funding: MSD Merck Sharp & Dohme AG. Disclosure: S. Popat: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Boehringer Ingelheim; Research grant / Funding (institution): Epizyme; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Research grant / Funding (institution): Clovis Oncology; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Research grant / Funding (institution): Lilly; Honoraria (self), Research grant / Funding (institution): Takeda; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self): Chugai Pharma; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Sharp & Dohme; Advisory / Consultancy: Guardant Health; Advisory / Consultancy: AbbVie. A. Curioni-Fontecedro: Honoraria (self), Advisory / Consultancy:
Volume 30 | Supplement 5 | October 2019
AstraZeneca; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Merck Sharp and Dohme; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Takeda. R. Shah: Advisory / Consultancy: Merck Sharp & Dohme; Advisory / Consultancy: Lilly. M. O’Brien: Advisory / Consultancy: Merck Sharp & Dohme; Advisory / Consultancy: BMS; Advisory / Consultancy: AbbVie; Advisory / Consultancy: Pierre fabre; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy, Teaching role for Roche: Roche. P. Fisher: Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Sharp & Dohme. D. Gilligan: Honoraria (self): Merck Sharp & Dohme. E. Nadal: Advisory / Consultancy: Merck Sharp & Dohme. R. L opez Castro: Honoraria (self), Travel / Accommodation / Expenses: Takeda; Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Boehringer Ingelheim; Honoraria (self), Research grant / Funding (self), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Travel / Accommodation / Expenses: Merck Serono; Honoraria (self), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy: Aristo. R. Garcıa Campelo: Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Sharp & Dohme. S. Peters: Honoraria (self): AbbVie; Honoraria (self): Amgen; Honoraria (self): AstraZeneca; Honoraria (self): Bayer; Honoraria (self): Biocartis; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Clovis; Honoraria (self): Daiichi Sankyo; Honoraria (self): Debiopharm; Honoraria (self): Lilly; Honoraria (self): Roche; Honoraria (self): Foundation Medicine; Honoraria (self): Illumina; Honoraria (self): Janssen; Honoraria (self): Merck Sharp and Dohme; Honoraria (self): Merck Serono; Honoraria (self): Merrimack; Honoraria (self): Novartis; Honoraria (self): Pharma Mar; Honoraria (self): Pfizer; Honoraria (self): Regeneron; Honoraria (self): Sanofi; Honoraria (self): Seattle Genetics ; Honoraria (self): Takeda. R.A. Stahel: Honoraria (self): AbbVie; Honoraria (self), Research grant / Funding (self): AstraZeneca; Honoraria (self), Research grant / Funding (self): Boehringer Ingelheim; Honoraria (self), Research grant / Funding (self): Merck Sharp & Dohme; Honoraria (self), Research grant / Funding (self): Pfizer; Honoraria (self), Research grant / Funding (self): Roche; Honoraria (self): Takeda; Research grant / Funding (self): BMS; Research grant / Funding (self): Genentech. All other authors have declared no conflicts of interest.
LBA92
Switch maintenance gemcitabine after first-line chemotherapy in patients with malignant mesothelioma: A multicenter open label phase II trial (NVALT19)
S.A. Burgers1, C. de Gooijer1, R. Cornelissen2, J.G. Aerts3, B. Biesma4, R.V. Heemst5, M. Youssef-El Soud6, H.J.M. Groen7, A.J. Staal-van den Brekel8, G. Bootsma9, J.H.E.M. Schijen10, P. Baas1, E. Giovannetti11, J.F. de Vries12, F.A. Hogenboom12, D.C.M. de Wit12, M.C.W. Mahn- Schaefers1, F. Lalezari13, V. van de Noort12, J. Stigt14 1 Thoracic Oncology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital (NKI-AVL), Amsterdam, Netherlands, 2Pulmonary Diseases, Erasmus University Medical Center, Rotterdam, Netherlands, 3Pulmonary Diseases, Erasmus University Medical Center, Rotterdam, Noord Brabant, Netherlands, 4Pulmonary Diseases, Jeroen Bosch Hospital, ’s-Hertogenbosch, Netherlands, 5Pulmonary Diseases, Deventer Hospital, Deventer, Netherlands, 6Pulmonary Diseases, Maxima Medisch Centrum, Eindhoven, Netherlands, 7Pulmonary Diseases, University Hospital Groningen (UMCG), Groningen, Netherlands, 8Pulmonary Diseases, ZGT Hengelo, Henglo, Netherlands, 9Pulmonary Diseases, Zuyderland Medical Center, Heerlen, Netherlands, 10Pulmonary Diseases, Elisabeth-Tweesteden Hospital, Tilburg, Netherlands, 11Medical Oncology, Vrije University Medical Centre (VUMC), Amsterdam, Netherlands, 12Biometrics, NVALT Study Centre, Amsterdam, Netherlands, 13Radiology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital (NKI-AVL), Amsterdam, Netherlands, 14Pulmonary Diseases, Isala, Zwolle, Netherlands Background: All malignant mesothelioma (MM) patients progress after first-line therapy. We examined whether switch maintenance gemcitabine in patients, who did not show progression after first-line platinum-pemetrexed, could prolong time to disease progression. Methods: NVALT19 was an open label, randomized phase II trial, conducted in The Netherlands. Main eligibility criteria were pathologically proven MM, ECOG-PS 0-2 and completion of 4-6 cycles of first-line platinum-pemetrexed without progression. Patients were randomized 1:1 between gemcitabine (1250 mg/m2 day 1 and 8 of 3 weekly schedule) or best supportive care (BSC). Gemcitabine was given until disease progression, severe toxicity or patient request for discontinuation. Primary endpoint was progression free survival (PFS) determined by local physician according to modified RECIST (mRECIST) or death in the intention-to-treat population. It was computed that 118 events would yield 90% power to detect an increase in PFS from median 3.5 months to median 6 months at 90% confidence level.
doi:10.1093/annonc/mdz394 | v931
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz394.092/5578400 by guest on 24 October 2019
A multicentre randomized phase III trial comparing pembrolizumab (P) vs single agent chemotherapy (CT) for advanced pre-treated malignant pleural mesothelioma (MPM): Results from the European Thoracic Oncology Platform (ETOP 915) PROMISE-meso trial
abstracts
v932 | Thoracic malignancies, other
Conclusions: Switch maintenance gemcitabine after first-line chemotherapy significantly improves the PFS in malignant mesothelioma, with a manageable toxicity profile. Clinical trial identification: NTR4132. Legal entity responsible for the study: Stichting NVALT studies. Funding: Dutch Cancer Society and Stichting NVALT studies. Disclosure: All authors have declared no conflicts of interest.
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz394.092/5578400 by guest on 24 October 2019
Results: Between March 2014 and February 2019, 130 patients were randomized, 65 in each arm. PFS was significantly longer with gemcitabine (median 6.2 months [range 4.6-8.7m]) than in the BSC arm (3.2 [2.8-4.2m]; hazard ratio 0.42; 95% confidence interval [CI], 0.28-0.63; p < 0.0001). The PFS probability at 12 months was 25% for Maintenance Gemcitabine (95% CI: 16.3 - 38.5%) and 3.3% for BSC (95% CI: 0.8 13%). Central revision of PFS, by a blinded radiologist, also showed significant benefit for gemcitabine (median 5.3 months [4.2-7.1m]) above BSC (2.8 [2.5-3.3m]; hazard ratio 0.42; 95% CI 0.28 to 0.62; p < 0.0001). Grade 3-4 adverse events (AE) occurred more in the gemcitabine arm (57% of patients) vs 13% in the BSC-arm. Neutropenia (22%), nausea (6%) and lung infection (5%) were most common treatment related grade III AE’s. Three patients (5%) experienced grade IV neutropenia. One patient died in the gemcitabine arm due to treatment related sepsis. Data on dose intensity will follow at ESMO 2019.
Annals of Oncology
Volume 30 | Supplement 5 | October 2019
S. Popat1, A. Curioni-Fontecedro2, V. Polydoropoulou3, R. Shah4, M. O’Brien5, A. Pope6, P. Fisher7, J. Spicer8, A. Roy9, D. Gilligan10, O. Gautschi11, E. Nadal12, W-D. Janthur13, R. L opez Castro14, R. Garcıa Campelo15, H. Roschitzki-Voser16, B. Ruepp16, S. Rusakiewicz17, S. Peters18, R.A. Stahel2 1 Medicine, Royal Marsden Hospital, London, UK, 2Center of Hematology and Oncology, University Hospital, Zurich, Switzerland, 3Statistics, Frontier Science Foundation-Hellas, Athens, Greece, 4Medical Oncology, Kent Oncology Centre, Maidstone, UK, 5Medicine, Royal Marsden Hospital Sutton, UK, 6Medical Oncology, Clatterbridge Cancer Centre, Liverpool, UK, 7Medical Oncology, Weston Park Hospital, Sheffield, UK, 8Comprehensive Cancer Centre, King’s College London Guy’s Hospital, London, UK, 9Medical Oncology, Plymouth Hospitals NHS Trust, Plymouth, UK, 10Medical Oncology, Addenbrooke’s Hospital, Cambridge, UK, 11Medical Oncology, Cantonal Hospital Luzern and Swiss Group for Clinical Cancer Research, Luzern, Switzerland, 12Catalan Institute of Oncology, L’Hospitalet Barcelona, Barcelona, Spain, 13Medical Oncology, Cantonal Hospital Aarau and Swiss Group for Clinical Cancer Research, Aarau, Switzerland, 14 Department of Oncology, Hospital Clınico Universitario de Valladolid, Valladolid, Spain, 15Medical Oncology, Hospital Teresa Herrera, La Coru~ na, Spain, 16Coordinating Office, European Thoracic Oncology Platform (ETOP), Bern, Switzerland, 17Centre of Experimental Therapies (CTE), Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland, 18Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland Background: MPM is an aggressive malignancy of increasing prevalence and poor prognosis. At relapse after platinum-based (pb) CT, single agent CT is commonly used and single arm trials of immune checkpoint inhibitors have demonstrated encouraging activity. Methods: PROMISE-meso is an open-label 1:1 randomized phase III trial investigating the efficacy of P (200 mg/Q3W) vs institutional choice single agent CT (gemcitabine or vinorelbine) in relapsed MPM patients (pts) failing one previous line of pb CT. Pts were of PS 0-1 and unselected for PD-L1 status. P beyond progression (PD) for clinical benefit and crossover to P at PD on CT were allowed. Primary endpoint was progression-free survival (PFS, RECIST 1.1) by independent radiological review (IR). The trial was designed to detect an increase in median PFS from 3.5 months (ms) to 6ms with P (HR ¼ 0.58, 80% power, 1-sided a ¼ 0.025). 142 pts were needed to observe the required 110 events. Secondary endpoints were overall survival (OS), investigator assessed (IA) PFS, objective response rate (ORR), adverse events (AE), while efficacy by PD-L1 status was exploratory. Results: Between 09/17 and 08/18, 144 pts were randomized, 73 to P and 71 to CT. At 20/02/19 data lock, 70 pts were on follow-up (median 12ms). Pts were of median age 70 years, 82% males, 77% poor EORTC prognostic score, 50% never smokers, 89% epithelioid histology and 65% (of 102 available) TPS1%. ORRs were 22% in P, 6% in CT (p ¼ 0.004). 62 IR PFS events were observed in P vs 56 in CT, median PFS 2.5ms (95%CI 2.1-4.2) vs 3.4ms (2.2-4.3), HR ¼ 1.06 (0.73–1.53), p ¼ 0.76. Median OS was 10.7ms for P vs 11.7ms for CT, HR ¼ 1.05 (0.66-1.67), p ¼ 0.85. 45 CT pts crossed over to P. Accounting for crossover yielded similar OS results. Treatment-related AEs grade 3 were experienced by 19% P vs 24% CT pts, one fatal per arm. Most common AEs were fatigue (19%) in P vs nausea (27%) and fatigue (31%) in CT. Conclusions: This is the first randomized trial evaluating the efficacy of P vs single agent CT in MPM pts progressing after or on previous pb CT. In unselected pts, whilst associated with an improved ORR, P does not improve PFS or OS over single agent CT. Clinical trial identification: NCT02991482. Legal entity responsible for the study: European Thoracic Oncology Platform (ETOP). Funding: MSD Merck Sharp & Dohme AG. Disclosure: S. Popat: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Boehringer Ingelheim; Research grant / Funding (institution): Epizyme; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Research grant / Funding (institution): Clovis Oncology; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Research grant / Funding (institution): Lilly; Honoraria (self), Research grant / Funding (institution): Takeda; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self): Chugai Pharma; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Sharp & Dohme; Advisory / Consultancy: Guardant Health; Advisory / Consultancy: AbbVie. A. Curioni-Fontecedro: Honoraria (self), Advisory / Consultancy:
Volume 30 | Supplement 5 | October 2019
AstraZeneca; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Merck Sharp and Dohme; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Takeda. R. Shah: Advisory / Consultancy: Merck Sharp & Dohme; Advisory / Consultancy: Lilly. M. O’Brien: Advisory / Consultancy: Merck Sharp & Dohme; Advisory / Consultancy: BMS; Advisory / Consultancy: AbbVie; Advisory / Consultancy: Pierre fabre; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy, Teaching role for Roche: Roche. P. Fisher: Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Sharp & Dohme. D. Gilligan: Honoraria (self): Merck Sharp & Dohme. E. Nadal: Advisory / Consultancy: Merck Sharp & Dohme. R. L opez Castro: Honoraria (self), Travel / Accommodation / Expenses: Takeda; Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Boehringer Ingelheim; Honoraria (self), Research grant / Funding (self), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Travel / Accommodation / Expenses: Merck Serono; Honoraria (self), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy: Aristo. R. Garcıa Campelo: Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Sharp & Dohme. S. Peters: Honoraria (self): AbbVie; Honoraria (self): Amgen; Honoraria (self): AstraZeneca; Honoraria (self): Bayer; Honoraria (self): Biocartis; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Clovis; Honoraria (self): Daiichi Sankyo; Honoraria (self): Debiopharm; Honoraria (self): Lilly; Honoraria (self): Roche; Honoraria (self): Foundation Medicine; Honoraria (self): Illumina; Honoraria (self): Janssen; Honoraria (self): Merck Sharp and Dohme; Honoraria (self): Merck Serono; Honoraria (self): Merrimack; Honoraria (self): Novartis; Honoraria (self): Pharma Mar; Honoraria (self): Pfizer; Honoraria (self): Regeneron; Honoraria (self): Sanofi; Honoraria (self): Seattle Genetics ; Honoraria (self): Takeda. R.A. Stahel: Honoraria (self): AbbVie; Honoraria (self), Research grant / Funding (self): AstraZeneca; Honoraria (self), Research grant / Funding (self): Boehringer Ingelheim; Honoraria (self), Research grant / Funding (self): Merck Sharp & Dohme; Honoraria (self), Research grant / Funding (self): Pfizer; Honoraria (self), Research grant / Funding (self): Roche; Honoraria (self): Takeda; Research grant / Funding (self): BMS; Research grant / Funding (self): Genentech. All other authors have declared no conflicts of interest.
LBA92
Switch maintenance gemcitabine after first-line chemotherapy in patients with malignant mesothelioma: A multicenter open label phase II trial (NVALT19)
S.A. Burgers1, C. de Gooijer1, R. Cornelissen2, J.G. Aerts3, B. Biesma4, R.V. Heemst5, M. Youssef-El Soud6, H.J.M. Groen7, A.J. Staal-van den Brekel8, G. Bootsma9, J.H.E.M. Schijen10, P. Baas1, E. Giovannetti11, J.F. de Vries12, F.A. Hogenboom12, D.C.M. de Wit12, M.C.W. Mahn- Schaefers1, F. Lalezari13, V. van de Noort12, J. Stigt14 1 Thoracic Oncology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital (NKI-AVL), Amsterdam, Netherlands, 2Pulmonary Diseases, Erasmus University Medical Center, Rotterdam, Netherlands, 3Pulmonary Diseases, Erasmus University Medical Center, Rotterdam, Noord Brabant, Netherlands, 4Pulmonary Diseases, Jeroen Bosch Hospital, ’s-Hertogenbosch, Netherlands, 5Pulmonary Diseases, Deventer Hospital, Deventer, Netherlands, 6Pulmonary Diseases, Maxima Medisch Centrum, Eindhoven, Netherlands, 7Pulmonary Diseases, University Hospital Groningen (UMCG), Groningen, Netherlands, 8Pulmonary Diseases, ZGT Hengelo, Henglo, Netherlands, 9Pulmonary Diseases, Zuyderland Medical Center, Heerlen, Netherlands, 10Pulmonary Diseases, Elisabeth-Tweesteden Hospital, Tilburg, Netherlands, 11Medical Oncology, Vrije University Medical Centre (VUMC), Amsterdam, Netherlands, 12Biometrics, NVALT Study Centre, Amsterdam, Netherlands, 13Radiology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital (NKI-AVL), Amsterdam, Netherlands, 14Pulmonary Diseases, Isala, Zwolle, Netherlands Background: All malignant mesothelioma (MM) patients progress after first-line therapy. We examined whether switch maintenance gemcitabine in patients, who did not show progression after first-line platinum-pemetrexed, could prolong time to disease progression. Methods: NVALT19 was an open label, randomized phase II trial, conducted in The Netherlands. Main eligibility criteria were pathologically proven MM, ECOG-PS 0-2 and completion of 4-6 cycles of first-line platinum-pemetrexed without progression. Patients were randomized 1:1 between gemcitabine (1250 mg/m2 day 1 and 8 of 3 weekly schedule) or best supportive care (BSC). Gemcitabine was given until disease progression, severe toxicity or patient request for discontinuation. Primary endpoint was progression free survival (PFS) determined by local physician according to modified RECIST (mRECIST) or death in the intention-to-treat population. It was computed that 118 events would yield 90% power to detect an increase in PFS from median 3.5 months to median 6 months at 90% confidence level.
doi:10.1093/annonc/mdz394 | v931
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz394.092/5578400 by guest on 24 October 2019
A multicentre randomized phase III trial comparing pembrolizumab (P) vs single agent chemotherapy (CT) for advanced pre-treated malignant pleural mesothelioma (MPM): Results from the European Thoracic Oncology Platform (ETOP 915) PROMISE-meso trial
abstracts
v932 | Thoracic malignancies, other
Conclusions: Switch maintenance gemcitabine after first-line chemotherapy significantly improves the PFS in malignant mesothelioma, with a manageable toxicity profile. Clinical trial identification: NTR4132. Legal entity responsible for the study: Stichting NVALT studies. Funding: Dutch Cancer Society and Stichting NVALT studies. Disclosure: All authors have declared no conflicts of interest.
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz394.092/5578400 by guest on 24 October 2019
Results: Between March 2014 and February 2019, 130 patients were randomized, 65 in each arm. PFS was significantly longer with gemcitabine (median 6.2 months [range 4.6-8.7m]) than in the BSC arm (3.2 [2.8-4.2m]; hazard ratio 0.42; 95% confidence interval [CI], 0.28-0.63; p < 0.0001). The PFS probability at 12 months was 25% for Maintenance Gemcitabine (95% CI: 16.3 - 38.5%) and 3.3% for BSC (95% CI: 0.8 13%). Central revision of PFS, by a blinded radiologist, also showed significant benefit for gemcitabine (median 5.3 months [4.2-7.1m]) above BSC (2.8 [2.5-3.3m]; hazard ratio 0.42; 95% CI 0.28 to 0.62; p < 0.0001). Grade 3-4 adverse events (AE) occurred more in the gemcitabine arm (57% of patients) vs 13% in the BSC-arm. Neutropenia (22%), nausea (6%) and lung infection (5%) were most common treatment related grade III AE’s. Three patients (5%) experienced grade IV neutropenia. One patient died in the gemcitabine arm due to treatment related sepsis. Data on dose intensity will follow at ESMO 2019.
Annals of Oncology
Volume 30 | Supplement 5 | October 2019