Highlights on GI Cancer – Gastroesophageal, Pancreatic and Hepatobiliary – 2

Dr Willem Lybaert, a medical oncologist at the VITAZ Sint-Niklaas & University Hospital Antwerp gives a nice summary of the oral abstract session on gastroesophageal, pancreatic and hepatobiliary tumours from ASCO 2024.

The ECOG-ACRIN trial on neo-adjuvant treatment for oesophageal adenocarcinoma and gastro-oesophageal junction tumours compared the CROSS regimen (carboplatin plus paclitaxel plus radiotherapy) to a modified regimen that added nivolumab. The results showed no increase in the pCR rate with the addition of nivolumab, indicating a negative outcome. Additionally, there was a high dropout rate from adjuvant treatment options after esophagectomy.

The RENAISSANCE trial on stomach cancer and gastroesophageal junction tumours with oligometastatic disease examined continuing FLOT chemotherapy (fluorouracil, leucovorin, oxaliplatin, and docetaxel) for four cycles, followed by either ongoing FLOT or surgery and then resuming FLOT. The results showed no OS benefit from surgery, attributed to surgical complications and discontinuation of FLOT. The subgroup with only retroperitoneal lymph node involvement showed a survival benefit from surgery.

The ARMANI study explored first-line treatments for gastric and gastroesophageal junction cancer with FOLFOX chemotherapy (fluorouracil, leucovorin, and oxaliplatin) for three months. Patients either continued with FOLFOX followed by 5-FU maintenance or switched to paclitaxel plus ramucirumab. The switch therapy showed an OS benefit and improved response rates, despite higher toxicity. A limitation was the lack of biomarker information, as only HER2-negative patients were studied.

The GIANT trial on elderly and vulnerable patients with metastatic pancreatic cancer compared reduced doses of gemcitabine plus abraxane versus liposomal irinotecan plus 5-FU and leucovorin. Both regimens resulted in OS <6 months, highlighting the need for careful consideration of whether to administer chemotherapy or opt for supportive care.

The PASS-01 phase 2 study in metastatic pancreatic cancer compared FOLFIRINOX to gemcitabine plus abraxane, focusing on the feasibility of in-depth molecular analyses rather than efficacy. Researchers used whole genome sequencing, RNA sequencing, and chemotherapy sensitivity profiling to guide second-line therapy based on biomarkers. This approach was feasible in 50% of cases requiring second-line therapy, emphasizing the importance of molecular analyses in treatment decisions.

The NRG Oncology/RTOG 0848 study on the resected head of pancreas carcinoma examined adjuvant chemotherapy with or without chemoradiotherapy. While the study showed no OS benefit for the entire cohort, it demonstrated a positive impact in node-negative patients. This study used gemcitabine or gemcitabine plus erlotinib, now considered outdated compared to FOLFIRINOX.

The ABC-07 study on first-line treatment for locally advanced cholangiocarcinoma compared cisplatin-gemcitabine chemotherapy with and without stereotactic body radiation therapy (SBRT). No OS benefit was observed with SBRT. Current treatments often include cisplatin plus gemcitabine with durvalumab or pembrolizumab. The study indicated that SBRT might reduce liver failure due to better local control.

In immunotherapy for HCC, a study examined regorafenib plus pembrolizumab as a second-line treatment, showing a very low response rate and concluding it was not beneficial due to lack of T-cell expansion and reduced macrophage function.

The highly anticipated CheckMate 9DW study focused on first-line treatment for HCC with nivolumab plus ipilimumab versus sorafenib or lenvatinib. The results were positive, with a median overall survival of 23 months. The Kaplan-Meier curves revealed that lenvatinib performed better in the first 12 months, while immunotherapy showed superior performance afterwards. This suggests a need for biomarkers to identify patients who may not benefit initially from nivolumab plus ipilimumab.