Highlights on GI cancer 1

Prof Eric Van Cutsem, a digestive oncologist at University Hospitals, Belgium, provided a comprehensive overview of key studies presented at ASCO 2024 in the session on colorectal and anal cancer. The session primarily highlighted strategic surgical studies and new treatments for metastatic colorectal cancer (CRC) and microsatellite instability-high (MSI-H) patients.

The TransMet study, a major highlight, explored liver transplantation for patients with liver-limited metastatic CRC. Strict criteria and a validation committee oversaw patient selection, comparing continued chemotherapy to liver transplantation followed by chemotherapy. Results showed significantly better long-term survival for the transplantation group, matching outcomes of liver transplants for non-cancerous conditions. This study suggests liver transplantation as a viable option for selected patients despite ethical concerns regarding liver availability and patient selection.

Dutch researchers conducted two notable studies on liver metastases from CRC, evaluating surgery versus ablation. The COLLISION study confirmed no significant difference in outcomes between surgery and ablation, validating ablation as a safe alternative. The ORCHESTRA study examined chemotherapy alone versus chemotherapy plus debulking surgery for unresectable CRC. Results showed no survival benefit from debulking surgery, indicating that palliative debulking does not improve outcomes, except in specific cases like large, painful ovarian metastases.

In MSI-H patients, the CheckMate 8HW study, presented by Heinz Lenz, compared chemotherapy to nivolumab plus ipilimumab (Nivo-Ipi) for metastatic CRC. Unlike previous studies with pembrolizumab, Nivo-Ipi showed significantly better progression-free survival, with no rapid progression observed. While Nivo-Ipi is emerging as a new standard, data from the nivolumab alone arm is awaited for definitive recommendations.

Additional studies on checkpoint inhibition in the preoperative setting included a Chinese study showing higher activity of combined PD-1 and CTLA-4 antibodies over PD-1 alone in stage 2 and 3 colon cancer. An English study demonstrated complete responses with pembrolizumab in MSI-H tumours, highlighting the efficacy of PD-1 blockade in early CRC treatment.

An intriguing phase 2 study introduced a new agent targeting adenosine triphosphate (ATP) in chemo-refractory patients. This study, involving a quadruple combination of FOLFOX, a PD antibody, bevacizumab, and Etruma, showed promising survival benefits compared to regorafenib, though further confirmation is needed. Other sessions introduced an antibody-drug conjugate targeting c-MET with a topoisomerase inhibitor payload, indicating significant advancements in treatment options for MSI-H patients. These findings underscore ongoing progress in combination therapies and novel agents for CRC, particularly in leveraging checkpoint inhibitors and antibody-drug conjugates for improved patient outcomes.