Safety and feasibility of adding tumor debulking to palliative chemotherapy in multi-organ metastatic colorectal cancer: The ORCHESTRA trial.

Abstract

3553 Background: For selected patients with oligometastatic colorectal cancer (mCRC), local treatment of metastases is standard of care based on retrospective reports showing long term survival rates. Local treatment of metastases is technically feasible in an increasing number of patients with multi-organ mCRC. It is unknown if patients with extensive disease will benefit from tumor debulking when added to first line palliative chemotherapy. The ORCHESTRA trial (NCT01792934) was designed to prospectively evaluate overall survival (OS) benefit from tumor debulking in patients with multi-organ mCRC. Methods: Patients with multi-organ mCRC were eligible if > 80% tumor debulking was deemed feasible by resection, radiotherapy and/or thermal ablative therapy. All patients received oxaliplatin based chemotherapy ± bevacizumab. In case of stable disease or response at first evaluation (9 weeks), patients were randomized to continuation of chemotherapy or tumor debulking followed by chemotherapy. Adverse events were reported. If patient withdrawal after randomization was < 10%, the study was deemed feasible. Study continuation was based on the interim report on safety and feasibility after inclusion of 100 (of 478) patients. Results: Patients were randomized to the standard (N = 43) or intervention arm (N = 45). No patients withdrew after randomization. In 6.8% of patients debulking was not performed due to progressive disease (N = 5) or death (N = 1) prior to local treatment. Two patients had no lesions left to treat, 37 patients underwent tumor debulking. In 15 patients (40%) 21 serious adverse events related to debulking were reported, 83.7% of patients had no SAEs or recovered within 30 days. Postoperative 90-day mortality was 2.7% (N = 1). Chemotherapy was resumed in 86.5% of patients, median time to restart was 12.7 weeks (SD 5.6) and 78.4% completed ≥24 weeks of chemotherapy. Conclusions: Tumor debulking is feasible and safe and does not prohibit administration of palliative chemotherapy in the majority of patients with multi-organ mCRC. The ORCHESTRA trial will continue accrual to determine whether the aim of > 6 months OS benefit from tumor debulking will be achieved. Clinical trial information: NCT01792934.