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Nivolumab (Opdivo) given in combination with sunitinib (Sutent) was active in patients with advanced bone sarcoma, according to findings from the phase 1b/2 IMMUNOSARC study (NCT03277924) published in Cancer.
Data from the study demonstrated that the 6-month progression-free survival (PFS) rate in evaluable patients who received the combination (n = 38) was 42% (95% CI, 27%-58%) per centralized radiologic assessment, meeting the primary end point of the trial. The 6-month PFS rate was 32% (95% CI, 18%-47%) per local radiologic assessment and at a median follow-up of 39.8 months (95% CI, 37.9-41.7), the median PFS per centralized and local assessment was 3.8 months (95% CI, 2.7-4.8) and 3.7 months (95% CI, 2.7-4.7), respectively.
Additionally, the overall response rate (ORR) per RECIST 1.1 criteria was 5%, which was comprised of all partial responses (PRs), and 50% of patients achieved stable disease. The median duration of response for PRs was 29 months (range, 8-51) and the duration of response for stable disease was 7 months (range, 1-51). The PRs occurred in a patient with dedifferentiated chondrosarcoma and a patient with chondroblastic osteosarcoma.
“These results are consistent with second and further‐line treatment regimens with drugs considered active in bone sarcoma and the primary end point was met,” the study authors wrote. “Despite those outcomes, this was a hypothesis‐generating trial, aiming to explore signals of activity of this combination that could eventually be integrated into future trials.”
Diving into the IMMUNOSARC Trial Design
IMMUNOSARC was a multicenter study that enrolled patients who were 18 to 80 years old with metastatic/advanced bone sarcomas in Spain and Italy. Eligible patients also needed to have experienced disease progression within 6 months prior to enrollment; measurable disease per RECIST 1.1 criteria; an ECOG performance status of 0 or 1; adequate laboratory values; a left ventricular ejection fraction of at least 50% by echocardiogram or MUGA scan; and adequate hepatic, renal, cardiac, and hematologic function.
Patients received 37.5 mg of sunitinib orally on days 1 through 14 and the agent was subsequently given at a dose of 25 mg. Intravenous nivolumab was administered at a dose of 3 mg/kg every 2 weeks starting at day 15.
The primary end point for phase 2 of the study was 6-month PFS rate per central radiology review. Secondary end points included PFS, overall survival (OS), ORR per RECIST 1.1 criteria, safety, and the collection of tissue samples for translational research.
At baseline, the median age in the overall population (n = 40) was 47 years (range, 21-74). Disease histologies consisted of osteosarcoma (42%), chondrosarcoma (25%), Ewing sarcoma (20%), dedifferentiated chondrosarcoma (10%), and undifferentiated pleomorphic sarcoma (2%). Most patients were male (67%), had metastatic disease (90%), had an ECOG performance status of 1 (72%), did not have resectable disease (95%), and received 1 to 2 prior lines of therapy (72%).
Exploring Additional Efficacy Findings and Safety Data
Additional findings showed that the median OS was 11.9 months (95% CI, 5.6-18.2); the 6-, 12-, and 18-month OS rates were 73% (95% CI, 59%-87%), 47% (95% CI, 30%-65%), and 37% (95% CI, 20%-54%), respectively. The centrally assessed median PFS among patients with osteosarcoma, conventional chondrosarcoma, Ewing sarcoma, and dedifferentiated chondrosarcoma was 3.5 months (95% CI, 1.1-6.0), 9.5 months (95% CI, 0.0-19.3), 5.4 months (95% CI, 0.4-10.5), and 1.8 months (95% CI, not applicable), respectively.
The study authors noted that the toxicity profile of nivolumab plus sunitinib was relevant; 17% of patients discontinued treatment due to toxicity and there was 1 instance of grade 5 pneumonitis. The most common any-grade treatment-related hematologic adverse effects (AEs) included leukopenia (37.5%), neutropenia (37.5%), thrombocytopenia (37.5%), and anemia (35.0%). The most common nonhematological AEs were hypertension (62.5%), fatigue (62.5%), and diarrhea (45.0%). Grade 3 or higher AEs included neutropenia (15.0%), hypertension (15.0%), and anemia (12.5%), among others.
“Overall, further research is needed to better understand the potential benefits of immunotherapy in bone sarcoma and identify biomarkers of response to these treatments,” the study authors wrote in their conclusion. “Based on this phase 1/2 trial finding, a correlative study with the NanoString PanCancer immune profiling panel in pre‐ and posttreatment biopsies is ongoing. An international expansion phase 2 trial [NCT03277924] in patients with selected sarcoma histotypes, dedifferentiated chondrosarcoma among bone sarcoma, is currently enrolling.”
Reference
Palmerini E, Lopez Pousa A, Grignani G, et al. Nivolumab and sunitinib in patients with advanced bone sarcomas: a multicenter, single-arm, phase 2 trial. Cancer. 2025;131(1):e35628. doi:10.1002/cncr.35628