Olaratumab in combination with doxorubicin plus ifosfamide
Olaratumab at 15 mg/kg has been shown to be safe in combination with doxorubicin plus ifosfamide in a Phase 1b study (NCT03283696), reported Sebastian Bauer, MD, of the West German Cancer Center, University of Duisburg-Essen, Essen, Germany, and his colleagues.
Given that 8 of 10 evaluable patients have completed the drug-limiting toxicity period without drug-limiting toxicities at the 15 mg/kg dose level of olaratumab, the study has proceeded to the next cohort. In those patients, an olaratumab loading dose of 20 mg/kg will be evaluated in cycle 1, followed by 15 mg/kg of olaratumab in subsequent cycles with the same doses of doxorubicin plus ifosfamide, the researchers wrote in their abstract.
The phase 1 trial enrolled 16 patients with advanced or metastatic soft tissue sarcomas and no prior lines of systemic therapy and ECOG performance status 0-1. Adequate follow up data was available for 10 patients.
Olaratumab, (Lartruvo), which binds platelet-derived growth factor receptor alpha (PDGFRα), was given at 15 mg/kg in combination with doxorubicin (75 mg/m2 on days 1-3) and ifosfamide (10 g/m2 on days 1-4) followed by mandatory granulocyte-colony-stimulating factor therapy in cycles 1-6 on a 21-day cycle. Doxorubicin was allowed to be administered by continuous infusion or bolus administration and with cardiac protection. Mesna dosing was at least 60% of the ifosfamide dose.
Two of the 10 patients had dose-limiting toxicities; one had Grade 4 febrile neutropenia and the other had Grade 3 febrile neutropenia and Grade 3 mucositis. Common related adverse events occurring in over 30% of patients included fatigue, anemia, neutropenia, thrombocytopenia, constipation, and nausea. One patient discontinued study treatment due to progressive disease, and all others were on study treatment as of data cutoff. Among 7 patients evaluated for tumor response assessment, 3 patients had a partial response according to RECIST and 3 further patients had stabilized disease as best overall response for a disease control rate of 86%.
Anthracycline-based regimen excels in FIGO-1 uterine leiomyosarcoma
Future trials to assess the efficacy of adjuvant chemotherapy in uterine leiomyosarcoma should incorporate anthracyclines, according to Roberta Sanfilippo, MD, of Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy, and her colleagues.
Disease-free survival was extended in patients with uterine leiomyosarcomas treated with anthracycline-based regimens as compared to gemcitabine and docetaxel, based on a retrospective analysis reported at the meeting by Dr. Sanfilippo.
They reviewed all patients with FIGO stage I uterine leiomyosarcomas who underwent hysterectomy with or without oophorectomy and were treated with adjuvant chemotherapy with either anthracycline-based or gemcitabine-based chemotherapy at two Italian centers.
Of 145 patients, 97 were treated with an anthracycline-based regimen and 48 with gemcitabine and docetaxel. The median number of cycles of anthracycline based regimen received was 4 (range 2-6) and with gemcitabine and docetaxel was 5 (range 3-7). Disease free survival was 31 months in patients treated with anthracycline-based chemotherapy and 19 months in patients treated with gemcitabine and docetaxel.
Trabectedin and low-dose radiotherapy
Trabectedin concurrent with low-dose radiotherapy is being examined as an option for patients with pulmonary metastatic soft tissue sarcoma (NCT02275286).