Highlights on GI cancer 2

Prof Alain Hendlisz, a digestive oncologist at the Institut Jules Bordet in Brussels, Belgium, provided a comprehensive overview of key studies presented at ASCO 2024 in the rapid oral abstract session on gastroesophageal, pancreatic, and hepatobiliary cancer.

The first abstract to discuss is from Zhang and colleagues in China, focusing on second-line treatment for gastric cancer after chemoimmunotherapy. This phase 2 randomised trial involved 59 patients treated with cadonilimab, a PD-1/CTLA-4 bispecific antibody, combined with pulocimab, an anti-VEGFR-2 mAb, and paclitaxel. The results were promising, showing an overall response rate of 50% in the cadonilimab-pulocimab arm compared to 36% in the standard arm. Additionally, the median PFS was 7 months in the cadonilimab-pulocimab arm versus 4.9 months in the standard arm, with median overall survival not yet reached. The significance of these results is tempered by the fact that there is no true standard arm in this study since pulocimab is not yet on the market. Typically, the standard treatment would be paclitaxel plus ramucirumab. Despite this, the data are promising, and a phase 3 trial is currently underway.

The second abstract is a Japanese study on borderline resectable pancreatic cancer, exploring neoadjuvant treatments. The study was based on the known benefit of gemcitabine plus radiotherapy for this cancer type. Two treatments were compared: gemcitabine plus nab-paclitaxel versus concurrent chemoradiotherapy with S-1 on irradiation days. Less than 50% of patients completed the preoperative treatment. Both OS and PFS were similar between the two arms, and the R0 resection rate was also comparable at 60% for each arm. This indicates that both strategies are equally effective, with no clear advantage for either. Notably, the standard arm did not include gemcitabine plus radiotherapy, deviating from typical standard protocols.

CAR T cells targeting GPC3 seem to offer a promising option for advanced unresectable hepatocellular cancer treatment. C-CAR031 is an autologous GPC3-directed CAR-T armoured with dominant negative TGF-b receptor II. A Chinese study reported the safety and preliminary efficacy of C-CAR031 in advanced HCC patients. 22 pts were evaluable for efficacy. Tumour reductions were observed in 90.9% of patients, not only in intrahepatic lesions but also in extrahepatic ones, with a median reduction of 44.0%. The disease control rate was 91%. The study showed a manageable safety profile and encouraging anti-tumour activity of C-CAR031 in heavily treated advanced HCC patients.

The final topic is a study presented by Jonathan Strosberg, which evaluated the safety, tolerability, and efficacy of ²¹²Pb-DOTAMTATE as a targeted alpha therapy for patients with unresectable or metastatic somatostatin receptor-expressing gastroenteropancreatic neuroendocrine tumours (SSTR+ GEP-NETs). The results were impressive, with an overall response rate of 55.6%. In cohort one, 36 patients were treated, showing a remarkable 17-month duration of response. Both PFS and median OS were not reached, indicating sustained efficacy. The toxicity profile was consistent with expectations for this type of therapy, suggesting that ²¹²Pb-DOTAMTATE could represent the future of peptide receptor radionuclide therapy.