Y Metaxas1, M Früh2, E I Eboulet3, F Grosso4, M Pless5, P A Zucali6, G L Ceresoli7, M Mark8, M Schneider3, A Maconi9, M Perrino6, C Biaggi-Rudolf3, P Froesch10, S Schmid11, C Waibel12, C Appenzeller11, D Rauch13, R von Moos8. 1. Department of Oncology/Haematology, Kantonsspital Graubünden, Chur, Switzerland. Electronic address: ioannis.metaxas@ksgr.ch. 2. Department of Medical Oncology and Haematology, Kantonsspital St. Gallen, St Gallen, Switzerland; University of Bern, Bern, Switzerland. 3. SAKK Coordinating Centre, Bern, Switzerland. 4. Mesothelioma Unit - Oncology, SS. Antonio and C. Arrigo Hospital, Alessandria, Italy. 5. Department of Medical Oncology and Haematology, Kantonsspital Winterthur, Winterthur, Switzerland. 6. Humanitas Cancer Centre, Humanitas Research Hospital, Rozzano, Italy. 7. Oncology Unit, Humanitas Clinic Gavazzeni, Bergamo, Italy. 8. Department of Oncology/Haematology, Kantonsspital Graubünden, Chur, Switzerland. 9. Scientific Research and Development Department, SS Antonio e Biagio e Cesare Arrigo, General Hospital, Alessandria, Italy. 10. Department of Oncology, Ospedale Regionale di Bellinzona e Valli, Bellinzona, Switzerland. 11. Department of Medical Oncology and Haematology, Kantonsspital St. Gallen, St Gallen, Switzerland. 12. Division of Haematology and Oncology, Kantonsspital Baden, Baden, Switzerland. 13. Oncology Centre, Hospital STS AG, Thun, Switzerland.
Abstract
BACKGROUND: Systemic second- and third-line therapies for malignant pleural mesothelioma (MPM) result in a median progression-free survival (mPFS) of <2 months and median overall survival (mOS) of 6-9 months. Lurbinectedin binds to the DNA of the regulatory region while inhibiting tumour-associated macrophage transcription. In early trials, encouraging outcomes occurred in patients (pts) with MPM treated with lurbinectedin. We aimed to generate lurbinectedin efficacy and safety data among pts with progressive MPM. PATIENTS AND METHODS: Pts with progressing MPM treated with first-line platinum-pemetrexed chemotherapy with or without immunotherapy received lurbinectedin monotherapy. Treatment was given intravenously at 3.2 mg/m2 dose every 3 weeks until progression or unacceptable toxicity. Using Simon's two-stage design, the primary endpoint, progression-free survival (PFS) at 12 weeks (PFS12wks), was met if achieved by ≥21 pts (p0 ≤35% versus p1 ≥55%). RESULTS: Forty-two pts from nine centres across Switzerland and Italy were recruited. Histology was epithelioid in 33 cases, sarcomatoid in 5, and biphasic in 4. Overall 10/42 (23.8%) underwent prior immunotherapy and 14/42 (33.3%) had progressed ≤6 months after first-line chemotherapy. At data cut-off PFS12wks was met by 22/42 pts (52.4%; 90% confidence interval (CI): 38.7% to 63.5%; P = 0.015) with an mPFS of 4.1 months and mOS of 11.1 months. The best response was complete and partial remission observed in one patient each and stable disease in 20 pts. The duration of disease control was 6.6 months (95% CI: 5.2-7.4). No significant difference in PFS12wks, mPFS, and mOS was recorded in epithelioid versus non-epithelioid cases and pts with prior immunotherapy versus those without. Similar mPFS but shorter mOS were observed among pts who progressed within ≤6 months after first-line chemotherapy. Lurbinectedin-related grade 3-4 toxicity was seen in 21 pts, mostly being neutropenia (23.8%) and fatigue (16.7%). CONCLUSIONS: The primary efficacy endpoint was reached with acceptable toxicity. Lurbinectedin showed promising activity regardless of histology, prior immunotherapy, or outcome on prior treatment. CLINICALTRIALS. GOV IDENTIFIER: NCT03213301.
BACKGROUND: Systemic second- and third-line therapies for malignant pleural mesothelioma (MPM) result in a median progression-free survival (mPFS) of <2 months and median overall survival (mOS) of 6-9 months. Lurbinectedin binds to the DNA of the regulatory region while inhibiting tumour-associated macrophage transcription. In early trials, encouraging outcomes occurred in patients (pts) with MPM treated with lurbinectedin. We aimed to generate lurbinectedin efficacy and safety data among pts with progressive MPM. PATIENTS AND METHODS: Pts with progressing MPM treated with first-line platinum-pemetrexed chemotherapy with or without immunotherapy received lurbinectedin monotherapy. Treatment was given intravenously at 3.2 mg/m2 dose every 3 weeks until progression or unacceptable toxicity. Using Simon's two-stage design, the primary endpoint, progression-free survival (PFS) at 12 weeks (PFS12wks), was met if achieved by ≥21 pts (p0 ≤35% versus p1 ≥55%). RESULTS: Forty-two pts from nine centres across Switzerland and Italy were recruited. Histology was epithelioid in 33 cases, sarcomatoid in 5, and biphasic in 4. Overall 10/42 (23.8%) underwent prior immunotherapy and 14/42 (33.3%) had progressed ≤6 months after first-line chemotherapy. At data cut-off PFS12wks was met by 22/42 pts (52.4%; 90% confidence interval (CI): 38.7% to 63.5%; P = 0.015) with an mPFS of 4.1 months and mOS of 11.1 months. The best response was complete and partial remission observed in one patient each and stable disease in 20 pts. The duration of disease control was 6.6 months (95% CI: 5.2-7.4). No significant difference in PFS12wks, mPFS, and mOS was recorded in epithelioid versus non-epithelioid cases and pts with prior immunotherapy versus those without. Similar mPFS but shorter mOS were observed among pts who progressed within ≤6 months after first-line chemotherapy. Lurbinectedin-related grade 3-4 toxicity was seen in 21 pts, mostly being neutropenia (23.8%) and fatigue (16.7%). CONCLUSIONS: The primary efficacy endpoint was reached with acceptable toxicity. Lurbinectedin showed promising activity regardless of histology, prior immunotherapy, or outcome on prior treatment. CLINICALTRIALS. GOV IDENTIFIER: NCT03213301.
Authors: M Mark; S Rusakiewicz; M Früh; S Hayoz; F Grosso; M Pless; P Zucali; G L Ceresoli; A Maconi; M Schneider; P Froesch; D Tarussio; F Benedetti; J Dagher; L Kandalaft; R von Moos; S Tissot-Renaud; S Schmid; Y Metaxas Journal: ESMO Open Date: 2022-04-12
Authors: Dario P Anobile; Paolo Bironzo; Francesca Picca; Marcello F Lingua; Deborah Morena; Luisella Righi; Francesca Napoli; Mauro G Papotti; Alessandra Pittaro; Federica Di Nicolantonio; Chiara Gigliotti; Federico Bussolino; Valentina Comunanza; Francesco Guerrera; Alberto Sandri; Francesco Leo; Roberta Libener; Pablo Aviles; Silvia Novello; Riccardo Taulli; Giorgio V Scagliotti; Chiara Riganti Journal: Cancers (Basel) Date: 2021-05-12 Impact factor: 6.639