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No survival benefit of tumour debulking for patients with multiorgan metastatic colorectal cancer

Presented by
Dr Else Gootjes, Erasmus MC, The Netherlands
Conference
ASCO 2024
Trial
Phase 3, ORCHESTRA
Tumour debulking in addition to standard palliative combination chemotherapy provides no survival benefit for patients with multiorgan metastatic colorectal cancer, according to results from the phase 3 ORCHESTRA trial.

Standard treatment of metastatic colorectal cancer is systemic therapy (chemotherapy and targeting agents) leading to a survival of approximately 30 months [1]. In addition, local debulking strategies are increasingly used [2]. However, the clinical benefit of these debulking strategies is uncertain.

The randomised, phase 3 ORCHESTRA trial (NCT01792934) aimed to evaluate the survival benefit of adding tumour debulking to standard palliative combination chemotherapy in patients with extensive multiorgan metastatic colorectal cancer. Previously, it was shown that local treatment in this population is feasible and safe and that tumour debulking results in more treatment-related toxicity but has no effect on health-related quality of life [3,4]. At ASCO, Dr Else Gootjes (Erasmus MC, The Netherlands) presented results of overall survival, the primary endpoint of ORCESTRA [5].

A total of 382 patients who demonstrated a response on systemic therapy (3 x CAPOX [B] or FOLFOX[B]) were 1:1 randomised to continuation of systemic therapy or local treatment (surgery, radiotherapy, and/or ablation) plus continuation of systemic therapy. Tumour debulking >80% was achieved in 72% of participants in the debulking arm. Median overall survival after a median follow-up of 32 months did not differ between treatment arms: 27.5 months and 30.0 months in the standard arm and debulking arm, respectively (HR 0.88 [95% CI 0.70-1.10]; P=0.23). In addition, no difference in median progression-free survival was observed (10.4 months vs 10.5 months). Outcomes were comparable in subgroups (number of metastatic sites, peritoneal involvement, duration of response to systemic therapy, completeness of debulking).

Based on these results, Dr Gootjes concluded that ‚ÄúTumour debulking in addition to standard palliative combination chemotherapy provides no survival benefit. Therefore, the increasing use of local therapies needs further consideration.‚ÄĚ

  1. Cremolini C, et al. J Clin Oncol 2020; 38: 3314-3324.
  2. Caroni C, et al. Crit Rev Oncol Hematol. 2023:186:103990.
  3. Gootjes EC, et al. Oncologist 2020; 25: e1195-e1201.
  4. Bakkerus L, et al. Natl Compr Canc Netw. 2023; 21: 1059-1066.
  5. Gootjes EC, et al. Primary endpoint analysis of the ORCHESTRA trial. Abstract LBA3502. ASCO Annual Meeting 2024, May 31-June 4, Chicago, IL, USA.

Medical writing support was provided by Marten Dooper, PhD.

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