Early-phase studies presented at the 2024 ESMO Congress highlight promising new therapeutic strategies for sarcoma, offering potential improvements in outcomes for this challenging group of cancers. Experts shared insights on trials involving novel combinations and maintenance therapies.
Palbociclib and Retifanlimab in Dedifferentiated Liposarcoma
A phase 2 trial (NCT04438824) evaluated the combination of palbociclib, a CDK4/6 inhibitor, and retifanlimab, an anti-PD-1 therapy, in patients with unresectable or metastatic dedifferentiated liposarcoma. The study showed a confirmed objective response rate (ORR) of 14.3% (95% CI, 4.7%-33.6%) among 28 patients who had received prior lines of therapy. The disease control rate was 50% (95% CI, 32.6%-67.4%). The median duration of response (DOR) was not reached (95% CI, 9.4-NR), the median progression-free survival (PFS) was 2.2 months (95% CI, 1.8-NR), and the median overall survival (OS) was 24.8 months (95% CI, 24.8-NR).
Dr. John Andrew Livingston from The University of Texas MD Anderson Cancer Center noted the efficacy signals warrant further investigation, with an ongoing randomized phase 2 study (NCT05694871) exploring palbociclib alone versus palbociclib plus cemiplimab in this patient population.
Regorafenib Maintenance in Soft Tissue Sarcomas
The phase 2 EREMISS trial (NCT03793361) investigated regorafenib maintenance therapy following initial doxorubicin-based chemotherapy in patients with non-adipocytic soft tissue sarcomas. Patients who achieved stable disease (SD) or partial response (PR) after 6 cycles of chemotherapy were randomized to receive regorafenib (n = 65) or placebo (n = 62).
The median PFS per blinded central review was 5.6 months (95% CI, 3.9-8.2) with regorafenib vs 3.5 months (95% CI, 1.8-3.6) with placebo (adjusted HR, 0.53; 95% CI, 0.36-0.78; P = .001). While the median OS was 27.6 months (95% CI, 19.9-33.0) with regorafenib vs 20.5 months (15.8-25.1) with placebo, this difference was not statistically significant (adjusted HR, 0.78; 95% CI, 0.50-1.22; P = .28).
Dr. Elise F. Nassif Haddad, also from MD Anderson Cancer Center, highlighted that this approach introduces a new concept of maintenance therapy in sarcoma, showing a trend for better OS and a significant benefit in PFS. This aligns with findings from the LMS04 trial, which demonstrated that trabectedin maintenance prolongs OS in leiomyosarcoma.
Botensilimab and Balstilimab in Metastatic Sarcoma
A phase 1 trial (NCT03860272) evaluated the combination of botensilimab, an anti-CTLA-4 antibody, and balstilimab, an anti-PD-1 antibody, in patients with relapsed/refractory metastatic sarcoma. Among efficacy-evaluable patients (n = 52), the ORR was 23% (95% CI, 13%-37%), and the median DOR was 21.7 months (95% CI, 3.4-NR). In patients with cutaneous or visceral angiosarcoma (n = 18), the ORR was 39% (95% CI, 17%-64%), with a median DOR of 21.7 months (95% CI, 1.9-NR).
Dr. Javier Martín-Broto from the University Hospital Fundacion Jimenez Diaz in Madrid, Spain, noted the striking ORR and DOR in the angiosarcoma subset, suggesting the combination's promise in this regard.
