LUME-Meso
Nintedanib in combination with pemetrexed and cisplatin for chemotherapy-naive patients with advanced malignant pleural mesothelioma (LUME-Meso): a double-blind, randomised, placebo-controlled phase 3 trial
Phase 2/3N = 458NCT01907100
- Population
- Chemotherapy-naive adults (18 years or older) with unresectable epithelioid malignant pleural mesothelioma and ECOG performance status 0-1 (phase 3 part). The phase II part enrolled chemotherapy-naive adults with unresectable non-sarcomatoid disease (epithelioid or biphasic).
- Design
- Phase II/III double-blind, randomised (1:1), placebo-controlled trial in first-line malignant pleural mesothelioma. Phase 3 part (120 centres, 27 countries; 458 randomised between 14 April 2016 and 5 January 2018): up to six 21-day cycles of pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 on day 1 with nintedanib 200 mg twice daily or matched placebo on days 2-21, then nintedanib or placebo maintenance if no progression. Primary endpoint investigator-assessed PFS by mRECIST in the ITT population. The phase II part (87 randomised, stratified by epithelioid or biphasic histology, primary endpoint PFS) was reported separately. ClinicalTrials.gov lists actual enrolment of 545 for both parts combined.
- Primary endpoint
- PFS
- Arms
- Nintedanib plus pemetrexed and cisplatin (experimental, n = 229): Pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 for up to six cycles with nintedanib 200 mg twice daily, then nintedanib maintenance
- Placebo plus pemetrexed and cisplatin (control, n = 229): Pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 for up to six cycles with matched placebo, then placebo maintenance
- People
- Scagliotti GV
PFSHR 1.01 (95% CI 0.79–1.30)Δ median PFS−0.2 monthsPFSHR 0.56 (95% CI 0.34–0.91)OSHR 0.77 (95% CI 0.46–1.29)
Show the numbers
| Endpoint | Analysis | Nintedanib plus pemetrexed and cisplatin | Placebo plus pemetrexed and cisplatin | Effect |
|---|---|---|---|---|
| PFSInvestigator-assessed progression-free survival by mRECIST, phase 3 part | primaryScagliotti 2019 | median 6.8 months (6.1–7.0) | median 7 months (6.7–7.2) | HR 1.01 (95% CI 0.79–1.30)P=0.91Phase 3 part, after 250 events. Grade 3 or worse neutropenia: 73 (32%) with nintedanib versus 54 (24%) with placebo. The authors state that the primary PFS endpoint was not met and that the phase II findings were not confirmed. The abstract prints no OS result. |
| PFSPhase II part: 87 randomised patients (analysis population not stated in the abstract)Progression-free survival, phase II part | primaryGrosso 2017 | — | — | HR 0.56 (95% CI 0.34–0.91)P=0.017Phase II part (87 randomised). The updated PFS analysis gave HR 0.54 (95% CI 0.33 to 0.87), P = .010. In the epithelioid subgroup, median PFS was 9.7 months with nintedanib versus 5.7 months with placebo (HR 0.49, 95% CI 0.30 to 0.82; P = .006). |
| OSPhase II part: 87 randomised patients (analysis population not stated in the abstract) | primaryGrosso 2017 | — | — | HR 0.77 (95% CI 0.46–1.29)P=0.319Phase II part, not a primary endpoint; the authors describe a trend. In the epithelioid subgroup, median OS was 20.6 months with nintedanib versus 15.2 months with placebo (HR 0.70, 95% CI 0.40 to 1.21; P = .197). |
| Endpoint | Analysis | Nintedanib plus pemetrexed and cisplatin | Placebo plus pemetrexed and cisplatin | Effect |
|---|---|---|---|---|
| PFSInvestigator-assessed progression-free survival by mRECIST, phase 3 part | primaryScagliotti 2019 | median 6.8 months (6.1–7.0) | median 7 months (6.7–7.2) | HR 1.01 (95% CI 0.79–1.30)P=0.91Phase 3 part, after 250 events. Grade 3 or worse neutropenia: 73 (32%) with nintedanib versus 54 (24%) with placebo. The authors state that the primary PFS endpoint was not met and that the phase II findings were not confirmed. The abstract prints no OS result. |
| PFSPhase II part: 87 randomised patients (analysis population not stated in the abstract)Progression-free survival, phase II part | primaryGrosso 2017 | — | — | HR 0.56 (95% CI 0.34–0.91)P=0.017Phase II part (87 randomised). The updated PFS analysis gave HR 0.54 (95% CI 0.33 to 0.87), P = .010. In the epithelioid subgroup, median PFS was 9.7 months with nintedanib versus 5.7 months with placebo (HR 0.49, 95% CI 0.30 to 0.82; P = .006). |
| OSPhase II part: 87 randomised patients (analysis population not stated in the abstract) | primaryGrosso 2017 | — | — | HR 0.77 (95% CI 0.46–1.29)P=0.319Phase II part, not a primary endpoint; the authors describe a trend. In the epithelioid subgroup, median OS was 20.6 months with nintedanib versus 15.2 months with placebo (HR 0.70, 95% CI 0.40 to 1.21; P = .197). |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 1.01 | 0.79–1.3 |
| PFS | 0.56 | 0.34–0.91 |
| OS | 0.77 | 0.46–1.29 |
- Nintedanib plus pemetrexed and cisplatin (experimental)
- Placebo plus pemetrexed and cisplatin (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Nintedanib plus pemetrexed and cisplatin | Placebo plus pemetrexed and cisplatin |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 4 | 66.5% | 67.3% |
| 9 | 40.0% | 41.0% |
| 13 | 26.6% | 27.6% |
| 18 | 16.0% | 16.8% |
Appears in
Sources
Scagliotti GV, Gaafar R, Nowak AK, Nakano T, van Meerbeeck J, Popat S, et al. Nintedanib in combination with pemetrexed and cisplatin for chemotherapy-naive patients with advanced malignant pleural mesothelioma (LUME-Meso): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet Respir Med. 2019;7(7):569-580.
Grosso F, Steele N, Novello S, Nowak AK, Popat S, Greillier L, et al. Nintedanib Plus Pemetrexed/Cisplatin in Patients With Malignant Pleural Mesothelioma: Phase II Results From the Randomized, Placebo-Controlled LUME-Meso Trial. J Clin Oncol. 2017;35(31):3591-3600.