LBA90 - A randomized phase II study of durvalumab and tremelimumab compared to doxorubicin in patients with advanced or metastatic soft tissue sarcoma (MEDISARC, AIO-STS-0415)

Background

Doxorubicin (DOX) is the standard of care (SOC) in patients with advanced or metastatic soft tissue sarcomas (STS) who cannot receive combination therapy. We tested whether the combination of durvalumab (DUR) and tremelimumab (TRE) improved overall survival (OS) compared to single agent DOX.

Methods

Treatment-naïve patients with chemo-sensitive advanced or metastatic STS who were not candidates for curative surgery or combination therapy were eligible. Key inclusion criteria were: ECOG performance status 0-2, grade 2 or 3, adequate organ function. Patients were 1:1 randomized (stratified by ECOG) to receive DUR 1.5g i.v. q4wks and TRE 75 mg i.v. 3x q4wks and q12wks thereafter for a maximum of 12 months or doxorubicin 75 mg/m² q3wks for up to 6 doses. OS was the primary endpoint. Secondary endpoints include 2-year OS rate, PFS, ORR (mRECIST 1.1), PFS, DOR, as well as safety (CTCTAE 4.03) and health-related quality of life (EORTC QLQ-C30). All randomized and treated subjects were included in the efficacy and safety analyses.

Results

Between April 2018 and September 2020 a total of 103 patients were randomized. 55% were female. Median age was 61 (r: 23-82) years. Most frequent STS were: leiomyosarcoma (LMS; 27%), undifferentiated pleomorphic sarcoma (UPS; 19%) and liposarcoma (LPS; 18%). PFS and 6-mo. PFS for DUR-TRE vs. DOX were 2.7 (95%CI 2.4-2.9) vs. 2.8 (95%CI 2.6-4.9) mo. (P=.401) and 11.4% vs. 33.6%, respectively. OS for DUR-TRE vs. DOX was 17.4 (95%CI 9.1-23.5) vs. 12.5 (95%CI 9.6-15.6) mo., which corresponded to a HR of 0.73 (95%CI 0.54-0.99; P=.185). 2-year OS was 35.7% vs. 29.0% for DUR-TRE vs. DOX, respectively. Adverse events (AE) of any grade and AE with grade ≥3 were 90.6% vs. 89.7% and 52.8% vs. 41.0% for DUR-TRE vs. DOX, respectively.

Conclusions

DUR-TRE showed comparable clinical activity to single agent DOX in treatment-naïve patients with STS. While OS favored DUR-TRE treatment, it did not reach significance. Our study indicated the principle activity of DUR-TREM in STS and warrants further studies.

Clinical trial identification

NCT03317457; EudraCT: 2016-004750-15.

Editorial acknowledgement

Legal entity responsible for the study

AIO-Studien-gGmbH.

Funding

AstraZeneca.

Disclosure

V. Gruenwald: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, EISAI, Ipsen, Janssen-Cilag, Merck Serono, MSD, Pfizer, Roche, Novartis, Astellas; Financial Interests, Personal, Advisory Board: BMS, EISAI, Merck Serono, MSD, Nanobiotix, Pfizer, Roche, Apogepha, EUSA Pharm, Debiopharm, Oncorena, PCI Biotech; Financial Interests, Personal, Stocks/Shares: BMS, MSD, AstraZeneca, Seattle Genetics; Financial Interests, Institutional, Steering Committee Member: BMS, Novartis; Financial Interests, Institutional, Research Grant: Ipsen, MSD, Pfizer, BMS; Financial Interests, Personal and Institutional, Steering Committee Member: Eisai, Ipsen; Financial Interests, Trial Chair: PharmaMar; Non-Financial Interests, Member: ASCO, German medical Oncology and Hematology Society; Non-Financial Interests, Advisory Role: German Cancer Society; Non-Financial Interests, Leadership Role: Working Group medical oncology; Other, Travel support to ESMO 2022: Pfizer; Other, Travel support for meeting: Merck Serono.