Online citations, reference lists, and bibliographies.
← Back to Search

Lurbinectedin As Second- Or Third-line Palliative Therapy In Malignant Pleural Mesothelioma: An International, Multi-centre, Single-arm, Phase II Trial (SAKK 17/16).

Y. Metaxas, M. Frueh, E. I. Eboulet, F. Grosso, M. Pless, P. Zucali, G. Ceresoli, M. Mark, M. Schneider, A. Maconi, M. Perrino, C. Biaggi-Rudolf, P. Froesch, S. Schmid, C. Waibel, C. Appenzeller, D. Rauch, R. von Moos
Published 2020 · Medicine

Cite This
Download PDF
Analyze on Scholarcy
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.
This paper references
Tremelimumab as second-line or third-line treatment in relapsed malignant mesothelioma (DETERMINE): a multicentre, international, randomised, double-blind, placebo-controlled phase 2b trial.
M. Maio (2017)
Second line therapy in malignant pleural mesothelioma: A systematic review.
W. Buikhuisen (2015)
Pembrolizumab as Palliative Immunotherapy in Malignant Pleural Mesothelioma
Y. Metaxas (2018)
A systematic review and meta-analysis of second-line therapies for treatment of mesothelioma.
F. Petrelli (2018)
The role of gemcitabine in the treatment of malignant mesothelioma.
H. Kindler (2002)
Prognostic Factors in the Treatment of Malignant Pleural Mesothelioma at a Large Tertiary Referral Center
R. Flores (2007)
Second-line chemotherapy in malignant pleural mesothelioma: results of a retrospective multicenter survey.
P. Zucali (2012)
Relapse pattern and second-line treatment following multimodality treatment for malignant pleural mesothelioma.
Arthur Kostron (2016)
Phase III trial of lurbinectedin versus PLD or topotecan in platinum-resistant ovarian cancer patients: Results of CORAIL trial.
S. Gaillard (2018)
Lurbinectedin reduces tumour-associated macrophages and the inflammatory tumour microenvironment in preclinical models
C. Belgiovine (2017)
Living with mesothelioma. A literature review.
S. Moore (2010)
Modified RECIST criteria for assessment of response in malignant pleural mesothelioma.
M. Byrne (2004)
Correlation of single arm versus randomised phase 2 oncology trial characteristics with phase 3 outcome.
J. Monzon (2015)
Nivolumab or nivolumab plus ipilimumab in patients with relapsed malignant pleural mesothelioma (IFCT-1501 MAPS2): a multicentre, open-label, randomised, non-comparative, phase 2 trial.
A. Scherpereel (2019)
Vinorelbine in pemetrexed-pretreated patients with malignant pleural mesothelioma.
P. Zucali (2014)
NGR-hTNF in combination with best investigator choice in previously treated malignant pleural mesothelioma (NGR015): a randomised, double-blind, placebo-controlled phase 3 trial.
V. Gregorc (2018)
Vorinostat in patients with advanced malignant pleural mesothelioma who have progressed on previous chemotherapy (VANTAGE-014): a phase 3, double-blind, randomised, placebo-controlled trial.
L. Krug (2015)
Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.
R. Stahel (2010)
Lurbinectedin (PM01183), an active compound in platinum-resistant/refractory ovarian cancer (PRROC) patients: Results of a two-stage, controlled phase II study.
A. Poveda (2014)
Phase III trial of pemetrexed plus best supportive care compared with best supportive care in previously treated patients with advanced malignant pleural mesothelioma.
J. Jassem (2008)
A design alternative for two-stage, phase II, multicenter cancer clinical trials.
J. Herndon (1998)
Vinca alkaloids in the therapeutic management of malignant pleural mesothelioma.
G. Ceresoli (2015)

This paper is referenced by
Semantic Scholar Logo Some data provided by SemanticScholar