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Trifluridine/tipiracil (FTD/TPI) is a novel oral formulation of two drugs with promising results in the treatment of metastatic colorectal cancer (mCRC).1 Trifluridine is a thymidine-based nucleoside analogue that, after intracellular phosphorylation, gets incorporated into DNA, causing DNA dysfunction.2 It was first identified by Callahan et al. in 1996 as an active impurity in the herbicide trifluralin, which […]

Highlights from ESMO GI 2024

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Published Online: Jul 30th 2024

The ESMO GI 2024 meeting, held this year in Munich, Germany, brought together researchers and clinicians from around the world to discuss recent developments in gastrointestinal malignancies. The conference highlighted the latest insights in the prevention, diagnosis and precision therapy of gastrointestinal cancers. These advancements aim to enhance patient care and pave the way for future research and treatment strategies. Here’s a closer look at some of the key updates from this year’s event.

Munich Germany

Significant progress in GEP-NET treatment with 177Lu-Dotatate

In what could be a major advancement for the treatment of advanced grade 2/3 well-differentiated gastroenteropancreatic neuroendocrine tumours (GEP-NETs), the phase III NETTER-2 trial has demonstrated that lutetium Lu 177 dotatate (177Lu-Dotatate) combined with octreotide significantly improves progression-free survival (PFS) compared to octreotide alone. The trial’s findings reveal a median PFS of 22.8 months for patients treated with 177Lu-Dotatate, compared to just 8.5 months for those on high-dose octreotide, representing a 72% reduction in the risk of disease progression or death.

The study, which enrolled 226 patients with advanced somatostatin receptor-positive GEP-NETs, randomly assigned participants to receive either 177Lu-Dotatate plus octreotide or high-dose octreotide alone. Results showed that patients in the 177Lu-Dotatate group experienced fewer progression events and deaths compared to the high-dose octreotide group.

177Lu-Dotatate was effective across various patient subgroups, including different ages, genders, races and tumour origins. The overall response rate was significantly higher in the 177Lu-Dotatate arm, with notable complete and partial responses.

The trial also assessed the quality of life, revealing similar times to deterioration between both treatment groups. Adverse effects were common but manageable, with nausea, diarrhoea and abdominal pain being the most frequent. Grade 3 or higher adverse effects were slightly more common in the 177Lu-Dotatate group.

These findings mark a significant step forward in the treatment of GEP-NETs, offering hope for improved outcomes in this patient population.

View the full abstract here

Could the CheckMate-8HW trial be a game-changer in metastatic colorectal cancer treatment?

The phase III CheckMate-6HW clinical trial has shown significant improvements in progression-free survival (PFS) with the use of frontline nivolumab combined with ipilimumab for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC). The trial’s interim analysis included 303 randomized patients, revealing a 79% reduction in disease progression or death risk for those on the dual immunotherapy regimen compared to chemotherapy.

At a median follow-up of 24.3 months, the PFS for the nivolumab/ipilimumab group had not been reached, vastly outperforming the chemotherapy group’s 5.9 months. This substantial benefit was consistent across various subgroups, including patients with specific genetic mutations and metastases.

Safety profiles for the combination therapy aligned with previous data, with manageable side effects and no new safety concerns. Treatment-related adverse events (TRAEs) were noted in 80% of the nivolumab/ipilimumab group compared to 94% in the chemotherapy group. Serious grade 3-4 TRAEs were less frequent in the immunotherapy arm.

If these results hold in further studies, nivolumab and ipilimumab could revolutionize the standard of care for MSI-H/dMMR metastatic colorectal cancer, offering a beacon of hope for patients battling this aggressive disease. The oncology community is watching closely as this promising treatment progresses through the clinical trial stages.

View the full abstract here

AI blood test shows promise for early detection of liver cancer

Findings from a recent study demonstrate that an artificial intelligence (AI) classifier, based on routine blood tests, can significantly improve early detection of hepatocellular carcinoma (HCC).

Early detection of HCC has long posed a challenge due to the limited sensitivity of the alpha-fetoprotein (aFP) test and the inconclusive results from ultrasonography in cirrhotic livers. Researchers utilized data from 13,703 patients, including 3,415 with HCC and 10,288 with chronic liver disease (CLD). By analyzing blood test results from up to one year before HCC diagnosis, the AI classifier was able to identify cancer with considerable accuracy. Sensitivity rates were 61.3% three months before diagnosis, gradually decreasing to 41.3% at nine to twelve months prior. Remarkably, this AI method consistently outperformed the traditional aFP test, which showed sensitivity rates below 45% at all intervals.

The study revealed that the AI approach could detect HCC an average of 167 days earlier than existing methods. Furthermore, routine blood tests were found to be five times more commonly used than aFP tests during the surveillance phase. This suggests a significant shift towards more frequent and reliable screening practices.

The findings highlight the potential of the AI-based blood test to detect HCC up to one year before clinical diagnosis in approximately 40% of patients. This advancement offers a critical window for timely early intervention, which could lead to reduced cancer mortality rates. As the medical community continues to seek improved diagnostic tools, this AI classifier represents a promising step forward in the fight against liver cancer.

Read the full abstract here

Significant improvement in quality-adjusted survival for metastatic colorectal cancer with fruquintinib

Combining fruquintinib with best supportive care has resulted in a notable improvement in quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) for patients with previously treated metastatic colorectal cancer (CRC), according to findings from the phase III FRESCO-2 trial. The trial’s post-hoc analysis revealed that patients receiving fruquintinib had a mean Q-TWiST of 6.25 months compared to 4.21 months for those given a placebo and best supportive care. This difference of 2.04 months was statistically significant.

Further, the mean time to disease progression with toxicity (TWiST) was significantly longer in the fruquintinib arm, at 4.06 months, compared to 1.92 months in the placebo group. Patients also spent more time with grade 3/4 treatment-emergent adverse effects (TEAEs) in the fruquintinib group (0.45 months) compared to the placebo group (0.21 months). Despite this, the overall duration between disease progression and death (REL) was similar between the two groups.

The trial, which included 691 patients from various regions, highlighted consistent improvements in Q-TWiST across all patient subgroups, with the exception of those with unknown primary tumour sites and right- or left-sided tumours. Sensitivity analysis confirmed a 33.0% relative improvement in Q-TWiST for those treated with fruquintinib.

These promising results supported the FDA’s approval of fruquintinib in November 2023 for metastatic CRC patients who had previously undergone treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, as well as an anti-VEGF agent. Patients with RAS wild-type disease who had received anti-EGFR therapy were also deemed eligible for fruquintinib treatment.

View the full abstract here

Disclosures: This article was created by the touchONCOLOGY team utilizing AI as an editorial tool (ChatGPT (GPT-4o) [Large language model]. https://chat.openai.com/chat.) The content was developed and edited by human editors. No funding was received in the publication of this article.

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