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Aldoxorubicin improves PFS in patients with relapsed soft tissue sarcoma

CHICAGO — Aldoxorubicin monotherapy appeared well tolerated and may improve outcomes compared with standard treatments for relapsed/refractory soft tissue sarcoma, according to results of a phase 3 clinical trial presented at the ASCO Annual Meeting.

Aldoxorubicin (CytRX Corporation) — a novel albumin-binding prodrug of doxorubicin — exhibited antitumor activity in several murine models and in a phase 2b study compared with doxorubicin.

Sant P. Chawla, MD, director of the Sarcoma Oncology Center in Santa Monica, California, and medical oncologist at Cedars-Sinai Comprehensive Cancer Center, and colleagues evaluated the safety and efficacy of aldoxorubicin compared with the investigator’s choice of treatment — dacarbazine, doxorubicin, pazopanib (Votrient, Novartis), ifosfamide or gemcitabine/docetaxel — among 433 patients with soft tissue sarcomas. Patients had leiomyosarcoma (42.5%), liposarcoma (15%), synovial sarcoma (9%), L-sarcomas (liposarcoma plus leiomyosarcoma, 57.5%) or other sarcoma types (33.5%). All patients had relapsed or were refractory to prior chemotherapy.

The researchers randomly assigned patients to receive 350 mg/m2 IV aldoxorubicin — equivalent to doxorubicin at 260 mg/m2 — or investigator’s choice therapy every 3 weeks. Most recruited patients derived from North America (72%), with the remainder from other parts of the world.

PFS with aldoxorubicin compared with investigator’s choice served as the primary endpoint. Secondary endpoints included tumor response, disease control rate, OS and safety.

Patients who received aldoxorubicin demonstrated longer median PFS than patients who received investigator’s choice, although this difference did not reach statistical significance (4.11 months vs. 2.96 months; HR = 0.81; 95% CI 0.64-1.03).

The PFS improvement reached significance in patients from North America (4.21 months vs. 2.96 months; HR = 0.71; 95% CI, 0.53-0.96) and patients with L-sarcomas (5.32 months vs. 2.96 months; HR = 0.62; 95% CI, 0.44-0.88).

Among the total population, patients who received aldoxorubicin achieved a higher disease control rate — which included complete response, partial response or stable disease for more than 4 months — than patients assigned investigator’s choice (30.3% vs. 20.9%; P = .028).

Patients from North America who received aldoxorubicin also had a higher disease control rate than patients assigned investigator’s choice (32.9% vs. 19.2%; P = .007).

The disease control rate among patients with L-Sarcomas was 37.5% for patients treated with aldoxorubicin and 23% for patients who received other therapies (P = .018).

Objective response rate doubled among patients assigned aldoxorubicin compared with other drugs (8.3% vs. 4.2%), Chawla said during his presentation.

More patients assigned aldoxorubicin experienced treatment-emergent grade 3 or grade 4 adverse events (61% vs. 46.4%), as well as serious adverse events (27% vs. 14%). However, more patients who experienced treatment-emergent adverse events from other treatments discontinued therapy (6.3% vs. 4.2%).

“Toxicity is expected ... [although] we were surprised patients did not lose their hair following 20 cycles of aldoxorubicin,” Chawla said.

Three deaths related to treatment occurred in the aldoxorubicin group compared with none in the investigator’s choice group.

“Taken together, [these data show] aldoxorubicin may be a superior anthracycline for treating advanced soft tissue sarcoma,” Chawla said. – by Melinda Stevens

Reference:

Chawla SP, et al. Abstract 11000. Presented at: ASCO Annual Meeting; June 2-6, 2017; Chicago.

Disclosure: Chawla reports research funding from CytRx Corporation. Please see the abstract for a list of all other researchers’ relevant financial disclosures.

CHICAGO — Aldoxorubicin monotherapy appeared well tolerated and may improve outcomes compared with standard treatments for relapsed/refractory soft tissue sarcoma, according to results of a phase 3 clinical trial presented at the ASCO Annual Meeting.

Aldoxorubicin (CytRX Corporation) — a novel albumin-binding prodrug of doxorubicin — exhibited antitumor activity in several murine models and in a phase 2b study compared with doxorubicin.

Sant P. Chawla, MD, director of the Sarcoma Oncology Center in Santa Monica, California, and medical oncologist at Cedars-Sinai Comprehensive Cancer Center, and colleagues evaluated the safety and efficacy of aldoxorubicin compared with the investigator’s choice of treatment — dacarbazine, doxorubicin, pazopanib (Votrient, Novartis), ifosfamide or gemcitabine/docetaxel — among 433 patients with soft tissue sarcomas. Patients had leiomyosarcoma (42.5%), liposarcoma (15%), synovial sarcoma (9%), L-sarcomas (liposarcoma plus leiomyosarcoma, 57.5%) or other sarcoma types (33.5%). All patients had relapsed or were refractory to prior chemotherapy.

The researchers randomly assigned patients to receive 350 mg/m2 IV aldoxorubicin — equivalent to doxorubicin at 260 mg/m2 — or investigator’s choice therapy every 3 weeks. Most recruited patients derived from North America (72%), with the remainder from other parts of the world.

PFS with aldoxorubicin compared with investigator’s choice served as the primary endpoint. Secondary endpoints included tumor response, disease control rate, OS and safety.

Patients who received aldoxorubicin demonstrated longer median PFS than patients who received investigator’s choice, although this difference did not reach statistical significance (4.11 months vs. 2.96 months; HR = 0.81; 95% CI 0.64-1.03).

The PFS improvement reached significance in patients from North America (4.21 months vs. 2.96 months; HR = 0.71; 95% CI, 0.53-0.96) and patients with L-sarcomas (5.32 months vs. 2.96 months; HR = 0.62; 95% CI, 0.44-0.88).

Among the total population, patients who received aldoxorubicin achieved a higher disease control rate — which included complete response, partial response or stable disease for more than 4 months — than patients assigned investigator’s choice (30.3% vs. 20.9%; P = .028).

Patients from North America who received aldoxorubicin also had a higher disease control rate than patients assigned investigator’s choice (32.9% vs. 19.2%; P = .007).

The disease control rate among patients with L-Sarcomas was 37.5% for patients treated with aldoxorubicin and 23% for patients who received other therapies (P = .018).

Objective response rate doubled among patients assigned aldoxorubicin compared with other drugs (8.3% vs. 4.2%), Chawla said during his presentation.

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More patients assigned aldoxorubicin experienced treatment-emergent grade 3 or grade 4 adverse events (61% vs. 46.4%), as well as serious adverse events (27% vs. 14%). However, more patients who experienced treatment-emergent adverse events from other treatments discontinued therapy (6.3% vs. 4.2%).

“Toxicity is expected ... [although] we were surprised patients did not lose their hair following 20 cycles of aldoxorubicin,” Chawla said.

Three deaths related to treatment occurred in the aldoxorubicin group compared with none in the investigator’s choice group.

“Taken together, [these data show] aldoxorubicin may be a superior anthracycline for treating advanced soft tissue sarcoma,” Chawla said. – by Melinda Stevens

Reference:

Chawla SP, et al. Abstract 11000. Presented at: ASCO Annual Meeting; June 2-6, 2017; Chicago.

Disclosure: Chawla reports research funding from CytRx Corporation. Please see the abstract for a list of all other researchers’ relevant financial disclosures.

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