(P 309) PHASE II TRIAL OF GEMCITABINE AND NAB-PACLITAXEL IN PATIENTS WITH RECURRENT SOFT TISSUE SARCOMA: A REPORT FROM THE NATIONAL PEDIATRIC CANCER FOUNDATION

Objective: The combination of gemcitabine and docetaxel is commonly used to treat patients with recurrent soft tissue sarcoma. Nab-paclitaxel is a taxane modified to improve drug exposure by increasing intratumoral accumulation, and it has additive preclinical activity with gemcitabine against sarcoma models. This combination is approved for pancreatic cancer, and using the dose and schedule for that disease we performed a phase II trial to assess the response rate of gemcitabine and nab-paclitaxel in pediatric, adolescent, and young adult patients with recurrent soft tissue sarcoma and measurable disease.

Methods: A Simon’s two-stage design was used to identify a response rate of ≥ 35%. Patients received nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) on days 1, 8, and 15 of a 28-day cycle. After some initial patients experienced myelosuppression, planned pegfilgrastim was added for subsequent patients. If myelosuppression persisted and patients had stable or responsive disease, a modified schedule was used consisting of nab-paclitaxel (100 mg/m2) and gemcitabine (675 mg/m2) on days 1 and 8 of a 21-day cycle. Cross-sectional imaging was performed at the completion of every two cycles with response assessed by RECIST 1.1. Progression-free survival (PFS) at six months was a secondary outcome measure.

Results: Twenty-eight eligible patients (13 male) with soft tissue sarcoma enrolled; the median age was 18 years (range 8-30 years). Ten patients had non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), and 18 had rhabdomyosarcoma (RMS), including 11 with FOXO1 fusions. Myelosuppression was common even with planned pegfilgrastim, and five patients received the modified 21-day schedule, which was well-tolerated and allowed continued treatment. Four of the total 28 patients were removed from study due to toxicity (cardiac, renal, neuropathic, and hematologic). For the patients with NRSTS (four with synovial sarcoma, three with desmoplastic small round cell tumor, and three with other diagnoses), the median number of cycles completed was 1.5 (range 0-4), and no patient responded. In contrast, for the patients with RMS, the median number of cycles completed was 2 (range 0-12), six (33%) received four or more cycles, and three, all with fusion-positive disease, had a confirmed response, for a response rate of 17%. The PFS at 6 months for patients with RMS was 28%, and only patients with fusion-positive RMS were progression-free at this time point. Table 1 presents the details of patients with RMS.

Conclusion: Although the response rate of 17% for patients with RMS fell below our established threshold, over one-fourth of the 11 patients with recurrent, fusion-positive disease experienced confirmed objective responses and PFS at 6 months. The use of pegfilgrastim and a modified 21-day schedule was successful in allowing for continued treatment despite myelosuppression.