Background: We evaluated the relationship between PFSR and OS in the Phase II part of LUME-Meso, a double-blind, placebo-controlled study that showed improved PFS (primary endpoint; hazard ratio [HR] = 0.56; 95% confidence interval [CI]: 0.34–0.91; p = 0.017), for N vs P; for OS HR = 0.77; 95% CI 0.46–1.29. Methods: Pts with unresectable MPM (ECOG PS 0–1), stratified by histology (epithelioid/biphasic), were randomized 1:1 to receive ≤6 cycles PEM (500 mg/m²)/CIS (75 mg/m²) on Day 1 + N or P (200 mg bid on Days 2–21), followed by N or P monotherapy maintenance. PFSR was defined as the proportion of pts who did not meet criteria for progressive disease (PD) at the specified time point (a ‘landmark analysis’). PFSR was assessed at 6 (PFSR6) and 8 (PFSR8) months. The association with OS was then evaluated based on the progression status at the landmark. Pts who died prior to the landmark were excluded from analysis. Results: 87 pts were randomized (N: 44; P: 43). The PFSR6 analysis included 71 pts (28 with PD and 43 without PD); subsequently there were 52 deaths. The PFSR8 analysis included 63 pts (32 with PD and 31 without PD); subsequently there were 45 deaths. There were more pts treated with N vs P who had not progressed at 6 (63% vs 37%) and 8 (71% vs 29%) months. Both PFSR6 and PFSR8 predicted OS (HR for PFSR6: 0.19; 95% CI: 0.11–0.35; HR for PFSR8: 0.18; 95% CI: 0.09–0.37). In the PFSR6 analysis, median OS was 22.8 months (95% CI: 15.6–28.4) in pts without PD prior to the landmark vs 6.1 months (95% CI: 3.3–7.0) in pts with PD prior to the landmark. In the PFSR8 analysis, median OS was 23.9 months (95% CI: 15.6–28.4) in pts without PD prior to the landmark vs 5.0 months (95% CI: 3.9–11.6) in pts with PD prior to the landmark. PFSR also predicted OS in pts with epithelioid histology at 6 months (n = 63; HR = 0.19; 95% CI: 0.10–0.36) and at 8 months (n = 57; HR = 0.20; 95% CI: 0.09–0.40). Conclusions: In our study in pts with MPM, landmark PFSR at 6 and 8 months predicts OS. These data are consistent with previously published findings. Phase III of LUME-Meso is ongoing (NCT01907100). Clinical trial information: NCT01907100