Reported by Prof Timon Vandamme, UZA Antwerpen
Two clinical trials were conducted to assess the role of radiotherapy in the treatment of locally advanced rectal cancer. In the CONVERT trial, neoadjuvant chemotherapy (nCT) with CAPOX alone was compared with neoadjuvant chemoradiotherapy (nCRT). The primary endpoint, complete pathological response (pCR), was achieved. The key parameter of interest, disease-free survival (DFS), will be reported after a 3-year follow-up.
The UNION trial compared short-course radiotherapy (SCRT) with CAPOX and camrelizumab to long-course radiotherapy (LCRT) with only CAPOX as perioperative treatment in locally advanced rectal cancer (LARC). However, SCRT did not prove to be non-inferior to LCRT, suggesting that LCRT still plays a significant role. This unexpected outcome could be attributed to the excellent performance of the control arm, contradicting recently published prospective data.
Regarding proximal rectal cancer, the ESMO2023 conference did not yield significant results for clinical practice.
The KRYSTAL-1 study investigated the efficacy of adagrasib, a KRAS-inhibitor, with or without cetuximab, an EGFR inhibitor, in KRAS G12C mutated colon cancer. Tumour biomarkers and genomic alterations were analyzed, but due to the small sample size and incomplete data collection, determining the optimal treatment for KRAS G12C-resistant patients remains challenging. The field of KRAS G12C inhibitors is expanding, with novel compounds undergoing trials.
The MOUNTAINEER study demonstrated the clinical benefits and good tolerance of the combination of tucatinib and trastuzumab. Molecular analysis revealed that HER2 is the disease driver, as no co-molecular alterations significantly impacted overall survival (OS) or progression-free survival (PFS). There is ongoing debate about the role of neoadjuvant treatment in colon cancer.
The FOxTROT trial investigated adding panitumumab to neoadjuvant FOLFOX treatment in stage 3 colon cancer, but the results were negative. RAS/BRAF wild-type patients with high EREG/AREG expression seemed to benefit, but the sample size was limited.
The CAIRO5 study evaluated neoadjuvant strategies for patients with liver metastasis from colon or colorectal cancer, distinguishing between right-sided tumours and/or RAS/BRAF mutant tumours and left-sided tumours or RAS-BRAF wild-type tumours. Despite better median PFS, overall response rates (ORR), and R0/1 resection rates in the first group and a better ORR in the second group, there was no difference in OS outcomes between the groups.
The PEGASUS trial explored a ctDNA-guided strategy in stage 2/ stage 3 patients post-resection to establish chemotherapy treatment and escalation or de-escalation strategies. While ctDNA showed promise, false-positive and false-negative results hindered its usability, necessitating further evaluation.
Robust evidence supports aspirin in colorectal cancer prevention, but the ASCOLT study did not demonstrate the benefit of a daily dose of 200 mg of aspirin in established colon cancer after surgery and completed chemotherapy. Further analysis from ongoing trials and meta-analyses may clarify aspirin’s value in the adjuvant setting for colon cancer.
References
Lin Z. – Neoadjuvant short-course radiotherapy followed by camrelizumab plus chemotherapy versus long-course chemoradiotherapy followed by chemotherapy in locally advanced rectal cancer: a randomized phase III trial (UNION). ESMO 2023 – LBA25
Ding P.-R. – Neoadjuvant Chemotherapy with CAPOX versus Chemoradiation for Locally Advanced Rectal Cancer with Uninvolved Mesorectal Fascia (CONVERT): Final Results of a Phase III Trial. ESMO 2023 – LBA26
Pelster M. S. – Adagrasib With or Without Cetuximab in Patients With KRASG12C-Mutated Colorectal Cancer (CRC): Analysis of Tumor Biomarkers and Genomic Alterations. ESMO 2023 -549O
Xu r-H. – Safety and efficacy of D-1553 in combination with cetuximab in KRAS G12C mutated colorectal cancer (CRC): a phase II study. ESMO 2023 – 550O
Strickler J.H. – Impact of baseline molecular alterations on the efficacy of tucatinib (TUC) plus trastuzumab (Tras) for HER2+, RAS WT metastatic CRC (mCRC) in MOUNTAINEER. ESMO2023 – 551O
Seligmann J. – FOxTROT: results of embedded phase II evaluating the addition of panitumumab (pan) to neo-adjuvant FOLFOX for patients (pts) with KRAS-wt colon cancer (CC) with extended biomarker panel. ESMO2023 – 552O
Punt C. – First-line systemic treatment in patients with initially unresectable colorectal cancer liver metastases (CRLM): overall survival of the phase III CAIRO5 study of the Dutch Colorectal Cancer Group. ESMO2023 – LBA27
Lonardi S. – The PEGASUS trial: post-surgical liquid biopsy-guided treatment of stage III and high-risk stage II colon cancer patients. ESMO2023 – LBA28
Chia J. – Aspirin After Standard Adjuvant Therapy for Colorectal Cancers (ASCOLT) – An International, Phase III, Randomised, Placebo-controlled Trial. ESMO2023 – LBA29
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