2018 World Congress on GI Cancer Highlights

Today-

Highlights from the 2018 World Congress on Gastrointestinal Cancer.

Welcome to OncLive News Network! I'm Gina Columbus.

Results of the IMblaze370 study presented at the meeting demonstrated that atezolizumab alone or in combination with cobimetinib failed to show superior overall survival versus regorafenib for patients with chemorefractory metastatic colorectal cancer.

In the phase III trial, the median OS with the combination of atezolizumab with cobimetinib was 8.9 months versus 8.5 months with the multikinase inhibitor regorafenib. For atezolizumab monotherapy, the median OS was 7.1 months with a hazard ratio of 1.19 compared with regorafenib.

Moreover, there were no differences in progression-free survival between the arms. For the combination versus regorafenib, the hazard ratio for PFS was 1.25. For atezolizumab versus regorafenib, the hazard ratio was 1.39.

Data showed that the objective response rate was 2.7% with the combination versus 2.2% in both monotherapy groups, and there were no complete responses. The median duration of response was 11.4, 4.8, and 9.2 months for the combination, atezolizumab monotherapy, and regorafenib, respectively.

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The phase III KEYNOTE-061 trial showed that second-line treatment with pembrolizumab did not significantly improve overall survival or progression-free survival in patients with advanced or metastatic gastric or gastroesophageal junction cancer with a PD-L1 combined positive score greater than or equal to 1 versus paclitaxel.

At a median follow-up of 7.9 months and in patients with a PD-L1 CPS greater than or equal to 1, the median OS was 9.1 months with pembrolizumab and 8.3 months with paclitaxel. This was associated with an 18% reduction in the risk for death with pembrolizumab.

Additionally, the median OS for patients with PD-L1 CPS less than 1 with pembrolizumab was 4.8 months versus 8.2 months with paclitaxel. Patients with a PD-L1 CPS greater than or equal to 10 treated with pembrolizumab experienced a median OS of 10.4 months compared with 8.0 months with paclitaxel.

Researchers noted that the pembrolizumab treatment effect for OS was greater in patients with an ECOG performance status of 0, PD-L1 CPS greater than or equal to 10 tumors, and microsatellite instability-high tumors. However, these were not the primary endpoints of the study.

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In gastric cancer, TAS-102 led to a 31% reduction in the risk of death compared with placebo in patients with heavily pretreated metastatic or advanced disease, according to findings from the phase III TAGS study.

The median overall survival was 5.7 months with TAS-102 versus 3.6 months for placebo. Twelve-month OS rates were 21.2% versus 13.0% for TAS-102 and placebo, respectively. This represents a significant improvement in survival for a poor prognosis group.

Moreover, the median PFS with TAS-102 was 2.0 versus 1.8 months with placebo, representing a 43% reduction in the risk of progression or death. The 6-month PFS rates were 21% versus 13%, respectively.

As of the data cut-off, 19 patients in the TAS-102 arm and 3 in the placebo group remained on treatment. Discontinuation was due to disease progression in 76% and 87% of patients in the TAS-102 and placebo arms, respectively.

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TAS-120 demonstrated a clinically meaningful benefit with a manageable toxicity profile in patients with cholangiocarcinoma harboring FGFR2 gene fusions, including patients who had progressed on an FGFR inhibitor.

In a phase I study, the highly selective, irreversible FGFR1-4 tyrosine kinase inhibitor induced a confirmed partial response in 7 of 24 patients. An additional 15 patients achieved stable disease. Overall, 20 patients had some level of tumor shrinkage.

The most frequent all-grade adverse events were expected and manageable, including hyperphosphatemia and cutaneous and gastrointestinal toxicity. Treatment-related grade 3 AEs occurred in 51.1% of patients, with the most common including hyperphosphatemia, ALT increase, palmar-plantar erythrodysesthesia syndrome, constipation, AST increase, and diarrhea.

TAS-120 was granted orphan drug status by the FDA in May 2018 for the treatment of patients with cholangiocarcinoma.

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Finally, results from the regorafenib dose optimization study, known as ReDOS, established that the strategy of escalating regorafenib from 80 mg to 160 mg per day was superior to starting at 160 mg daily for patients with refractory metastatic colorectal cancer.

Weekly dose-escalation of regorafenib may become the new standard dosing for these patients being treated with the multikinase inhibitor.

Of the 54 patients enrolled in the dose-escalation experimental arm, 43% initiated the third cycle of therapy, versus only 24% of the 62 patients in the control arm.

These results met the primary endpoint of the study, which was proportion of patients who initiate a third cycle in the escalation arm versus the control arm. The superiority of the experimental arm over the control arm was also a prime consideration.

Overall survival was a secondary endpoint on this study. The experimental arm was superior to the control arm in terms of survival, but it was not statistically significant as an endpoint.

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That’s all for today.

Thank you for watching OncLive News Network! I'm Gina Columbus.