ORCHESTRA Primary Outcome Analysis: Additional Tumor Debulking for Multiorgan mCRC

The phase 3, investigator-initiated ORCHESTRA trial does not support additional tumor debulking to standard first-line palliative systemic therapy to improve overall survival (OS) for patients with multiorgan metastatic colorectal cancer (mCRC).

The primary outcome analysis was presented as a late-breaking abstract at the 2024 American Society of Clinical Oncology Annual Meeting.

ORCHESTRA was conducted to prospectively evaluate OS benefit from tumor debulking in addition to standard palliative systemic therapy in these patients. Local therapy of metastatic sites is often discussed with patients as part of the treatment plan. However, evidence to support additional local therapy over systemic therapy alone is lacking.

Elske C. Gootjes, MD, PhD, and colleagues from Radboud UMC (the Netherlands) enrolled 454 patients across 28 hospitals from May 2013 to May 2023. Patients were eligible if at least 80% tumor debulking was feasible by resection, radiotherapy, and/or thermal ablative therapy at the start of first-line palliative systemic therapy. Upon clinical benefit after 3 to 4 cycles of capecitabine or 5-fluorouracil/leucovorin and oxaliplatin ± bevacizumab, 382 patients were randomized (1:1) to continuation with systemic therapy alone (standard arm) or tumor debulking followed by restart of the systemic therapy (experimental arm).

The primary end point of the study was OS, and secondary end points included progression-free survival (PFS) and treatment-related adverse events.

At the data cutoff of April 4, 2024, a total of 153 OS events were observed in the standard arm versus 155 in the experimental arm.

After a median follow-up of 32.3 months, the median OS was 27.5 months versus 30.0 months, respectively (hazard ratio [HR], 0.88; 95% CI, 0.70-1.10; P=.225), and the median PFS was 10.4 months versus 10.5 months, respectively (HR, 0.83; 95% CI, 0.67-1.02; P=.076).

“Additional tumor debulking to standard first-line palliative systemic therapy failed to improve OS for patients with multiorgan mCRC,” Dr. Gootjes and colleagues concluded. “The increasing use of local therapies for patients with mCRC needs further consideration.”