Abstract 1495P
Background
This phase I/II trial aimed to investigate the safety and activity of gemcitabine and nab-paclitaxel (nab-pc) in advanced, relapsed soft tissue sarcoma (STS). (NCT03524898).
Methods
We included patients with STS who progressed after minimum of one line of standard treatment with ECOG 0-2,life expectancy of >3 months and adequate organ function. The primary endpoint in phase II was progression-free rate (PFR) at 3 months (H0: 20%, H1: 40%). A Simon’s optimal two-stage phase II design with a significance level of 0.1 and a power of 0.9 required a total sample size of 37 patients. Secondary endpoints included progression-free survival (PFS), adverse events (AEs), overall survival (OS) and patient-reported outcomes. Efficacy analysis was by intention-to-treat.
Results
We included 39 patients from 8 Swiss institutions. Six patients were treated in the phase 1 part of with nab-pc 150 mg/m2 and gemcitabine 1000mg/m2 every two weeks. No dose limiting toxicities (DLTs) occurred and this was defined as the recommended phase 2 dose (RP2D. In total, 56.4% of the patients had grade 3 STS, 77% had received one prior line of palliative systemic treatment, . At a median follow-up time of 26.4 months, the 3 months PFR (CR/PR/SD rate) was 56.4% (95% confidence interval (CI) 39.6 - 72.2%). Three-months and 6-months PFS based on Kaplan-Meier analysis were 58.4% (95% CI: 41.3 - 72.1%) and 44.6% (95% CI: 28.4 - 59.5%), respectively. Median PFS was 5.3 months (95% CI: 1.4 - 8.2) and median OS was 13.3 months (95% CI: 10.5 - 26.5). ORR according to RECIST1.1 was 10.5% (95% CI: 2.9 - 24.8%).The 3m PFSR in the LMS group was superiori to the recent EORT efficacy thershold.The most common treatment-related AE (TRAE) of grade ≥ 3 was neutropenia (grade 3 events in 15.4%, grade 4 events in 2.6%). TRAE grade 1 and grade 2 peripheral sensory neuropathy (PNP) occurred in 12.8% and 23.1%, respectively, with no–severe PNP. Patient-reported symptoms and their interferences with daily living remained stable over the first 3 months except for a significant increase in peripheral neuropathy.
Conclusions
Biweekly nab-pac and gemcitabine is an active combination in pretreated STS with manageable toxicity. This regimen should be considered for further exploration.
Clinical trial identification
NCT03524898.
Editorial acknowledgement
The authors acknowledge the support of Swiss League, Schweizerische Stiftung für klinische Krebsforschung,Celgene Corporation for this study and of the State Secretariat for Education, Research and Innovation (SERI)
Legal entity responsible for the study
SAKK Swiss Group for Clinical Cancer Research.
Funding
Swiss League, Schweizerische Stiftung für klinische Krebsforschung,Celgene Corporation for this study and of the State Secretariat for Education, Research and Innovation (SERI) Swiss League, Schweizerische Stiftung für klinische Krebsforschung,Celgene Corporation for this study and of the State Secretariat for Education, Research and Innovation (SERI) Swiss League, Schweizerische Stiftung für klinische Krebsforschung, Celgene Corporation (providing NAB-PACLITAXEL), State Secretariat for Education, Research and Innovation (SERI).
Disclosure
A. Digklia: Financial Interests, Institutional, Invited Speaker: PharmaMar; Financial Interests, Institutional, Research Grant: BMS. C. Britschgi: Financial Interests, Institutional, Advisory Board: Roche, Takeda, AstraZeneca, Pfisen, Janssen, Boehringer Ingelheim. M. Joerger: Financial Interests, Institutional, Research Grant: AstraZeneca, Basilea Pharmaceutica, Bayer, BMS, Immunophotonics, Innomedica, MSD, Novartis, Roche, Takeda; Financial Interests, Institutional, Other, Travel grant: BMS, Roche, MSD. I. Colombo: Financial Interests, Institutional, Advisory Board: AstraZeneca, GlaxoSmithKline, Novartis, Merck Sharp and Dohme; Financial Interests, Institutional, Funding: Merck Sharp and Dohme, Bayer, Oasmia; Financial Interests, Institutional, Other, Travel grant: Tesaro. All other authors have declared no conflicts of interest.