Lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma: an international, multi-centre, single-arm, phase II trial (SAKK 17/16)

Publikation

Lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma: an international, multi-centre, single-arm, phase II trial (SAKK 17/16)

Wissenschaftlicher Artikel/Review - 16.01.2020

Metaxas Y, von Moos R, Rauch D, Appenzeller Christina, Waibel C, Schmid S, Froesch P, Biaggi-Rudolf C, Perrino M, Maconi A, Schneider M, Mark M, Ceresoli G L, Zucali P A, Pless M, Grosso F, Eboulet E I, Früh Martin, Swiss Group for Clinical Cancer Research (SAKK)

Zitation

Metaxas Y, von Moos R, Rauch D, Appenzeller C, Waibel C, Schmid S, Froesch P, Biaggi-Rudolf C, Perrino M, Maconi A, Schneider M, Mark M, Ceresoli G, Zucali P, Pless M, Grosso F, Eboulet E, Früh M, Swiss Group for Clinical Cancer Research (SAKK). Lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma: an international, multi-centre, single-arm, phase II trial (SAKK 17/16). Ann Oncol 2020; 31:495-500.

Art

Wissenschaftlicher Artikel/Review (Englisch)

Zeitschrift

Ann Oncol 2020; 31

Veröffentlichungsdatum

16.01.2020

eISSN (Online)

1569-8041

Seiten

495-500

Kurzbeschreibung/Zielsetzung

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/m 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 (PFS), 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 PFS 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 PFS 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.