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2018 Gastrointestinal Cancers Symposium Highlights

Gina Columbus
Published: Monday, Jan 29, 2018



Today, highlights from the 2018 Gastrointestinal Cancers Symposium.

Hello and welcome to OncLive News Network. I'm Gina Columbus.

In hepatocellular carcinoma, phase III findings of the CELESTIAL trial presented during the meeting showed that treatment with cabozantinib improved median overall survival by 2.2 months versus placebo for patients with previously treated advanced disease.

In the double-blind trial, median OS with cabozantinib was 10.2 months versus 8.0 months with placebo, representing a 24% reduction in the risk of death. The median progression-free survival with cabozantinib was 5.2 months versus 1.9 months for placebo. This led to a 56% reduction in the risk of progression or death with the targeted therapy.

Based on these results, Exelixis, the company developing the multikinase inhibitor, plans to submit a supplemental new drug application to the FDA before the end of the first quarter. The agent is already approved as a treatment for patients with renal cell carcinoma and medullary thyroid cancer.

*****************************************

Also presented during the meeting were the phase II results of the ReDOS trial, a dose optimization study of regorafenib in metastatic colorectal cancer.

The findings showed that a weekly dose-escalation strategy of regorafenib beginning at 80 mg and ending at 160 mg was found to be superior than the previously standard starting dose of 160 mg in patients with mCRC.

Results showed that median overall survival was improved in the dose-escalation arm versus the standard arm, at 9 months versus 5.9 months, respectively. Additionally, the median progression-free survival was 2.5 months and 2.0 months for the dose-escalation and standard arms, respectively. Investigators noted that toxicity was more favorable in the dose-escalation arm, and quality of life parameters were improved as well.

*****************************************

In patients with heavily pretreated gastrointestinal stromal tumors, nivolumab alone and in combination with ipilimumab induced responses, according to interim data.

In the study, patients with advanced/metastatic GIST and an ECOG performance status of 0 or 1 who progressed on imatinib were randomized to either nivolumab alone or nivolumab plus ipilimumab for up to 2 years. The primary endpoint was the objective response rate by RECIST 1.1 criteria.

The first 14 patients enrolled in the randomized phase II study showed stable disease as best response in 3 of 7 patients treated with nivolumab monotherapy and 1 partial response and 2 patients with stable disease among those receiving both nivolumab and ipilimumab. The responses have been durable.

Additionally, the median progression-free survival was 8.6 weeks in the nivolumab arm and 9.86 weeks in the nivolumab plus ipilimumab arm. Fatigue, arthralgia, pruritus, and rash have been the main treatment-related adverse events.

*****************************************

Phase Ia/b findings presented at the meeting showed that the combination of ramucirumab plus durvalumab elicited antitumor activity in patients with previously treated advanced gastric or gastroesophageal junction adenocarcinoma.

Preclinical evidence suggests blocking VEGFR-2 and the PD-1/PD-L1 pathway induces synergistic antitumor effects. This promotes access of cytotoxic T cells to tumors, while avoiding the exhaustion of T cells.

In the ongoing, multi-cohort study of 29 patients receiving the combination, results showed that 17% achieved a confirmed partial response. Additionally, the overall response rate ws 36% for patients with PD-L1 expression greater than 25%, and median progression-free survival was 2.6 months.

Treatment-emergent adverse events occurred in all 29 patients, with 21 patients experiencing events that were grade 3/4. Although treatment-related adverse events occurred in 24 patients, no one discontinued treatment.

******************************

Finally, treatment with pembrolizumab was found to elicit promising progression-free survival and overall survival results in patients with advanced hepatocellular carcinoma who received previous treatment with sorafenib, according to phase II findings of the KEYNOTE-224 study.

Of 105 patients enrolled in the single-arm, open-label trial, the objective response rate with pembrolizumab was 16.3%, with 1 complete response. The median PFS was 4.8 months and the median OS has not been reached. The 6-month PFS and OS rates were 43.1% and 77.9%, respectively. Treatment remained ongoing in 23 patients.

In addition, the disease control rate was 61.5%. Best overall response was a partial response in 15.4%, CR in 1%, and stable disease in 45.2%. In the responders, the median time to response was 2.1 months. Ninety-four percent of responders were estimated to have a response duration of more than 6 months, and the median duration of response was 8.2 months.

The phase III KEYNOTE-240 is currently assessing pembrolizumab for pretreated patients with HCC, with a primary endpoint of OS.

That's all for today! Thank you for watching OncLive News Network. I'm Gina Columbus.

******************************
 
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Today, highlights from the 2018 Gastrointestinal Cancers Symposium.

Hello and welcome to OncLive News Network. I'm Gina Columbus.

In hepatocellular carcinoma, phase III findings of the CELESTIAL trial presented during the meeting showed that treatment with cabozantinib improved median overall survival by 2.2 months versus placebo for patients with previously treated advanced disease.

In the double-blind trial, median OS with cabozantinib was 10.2 months versus 8.0 months with placebo, representing a 24% reduction in the risk of death. The median progression-free survival with cabozantinib was 5.2 months versus 1.9 months for placebo. This led to a 56% reduction in the risk of progression or death with the targeted therapy.

Based on these results, Exelixis, the company developing the multikinase inhibitor, plans to submit a supplemental new drug application to the FDA before the end of the first quarter. The agent is already approved as a treatment for patients with renal cell carcinoma and medullary thyroid cancer.

*****************************************

Also presented during the meeting were the phase II results of the ReDOS trial, a dose optimization study of regorafenib in metastatic colorectal cancer.

The findings showed that a weekly dose-escalation strategy of regorafenib beginning at 80 mg and ending at 160 mg was found to be superior than the previously standard starting dose of 160 mg in patients with mCRC.

Results showed that median overall survival was improved in the dose-escalation arm versus the standard arm, at 9 months versus 5.9 months, respectively. Additionally, the median progression-free survival was 2.5 months and 2.0 months for the dose-escalation and standard arms, respectively. Investigators noted that toxicity was more favorable in the dose-escalation arm, and quality of life parameters were improved as well.

*****************************************

In patients with heavily pretreated gastrointestinal stromal tumors, nivolumab alone and in combination with ipilimumab induced responses, according to interim data.

In the study, patients with advanced/metastatic GIST and an ECOG performance status of 0 or 1 who progressed on imatinib were randomized to either nivolumab alone or nivolumab plus ipilimumab for up to 2 years. The primary endpoint was the objective response rate by RECIST 1.1 criteria.

The first 14 patients enrolled in the randomized phase II study showed stable disease as best response in 3 of 7 patients treated with nivolumab monotherapy and 1 partial response and 2 patients with stable disease among those receiving both nivolumab and ipilimumab. The responses have been durable.

Additionally, the median progression-free survival was 8.6 weeks in the nivolumab arm and 9.86 weeks in the nivolumab plus ipilimumab arm. Fatigue, arthralgia, pruritus, and rash have been the main treatment-related adverse events.

*****************************************

Phase Ia/b findings presented at the meeting showed that the combination of ramucirumab plus durvalumab elicited antitumor activity in patients with previously treated advanced gastric or gastroesophageal junction adenocarcinoma.

Preclinical evidence suggests blocking VEGFR-2 and the PD-1/PD-L1 pathway induces synergistic antitumor effects. This promotes access of cytotoxic T cells to tumors, while avoiding the exhaustion of T cells.

In the ongoing, multi-cohort study of 29 patients receiving the combination, results showed that 17% achieved a confirmed partial response. Additionally, the overall response rate ws 36% for patients with PD-L1 expression greater than 25%, and median progression-free survival was 2.6 months.

Treatment-emergent adverse events occurred in all 29 patients, with 21 patients experiencing events that were grade 3/4. Although treatment-related adverse events occurred in 24 patients, no one discontinued treatment.

******************************

Finally, treatment with pembrolizumab was found to elicit promising progression-free survival and overall survival results in patients with advanced hepatocellular carcinoma who received previous treatment with sorafenib, according to phase II findings of the KEYNOTE-224 study.

Of 105 patients enrolled in the single-arm, open-label trial, the objective response rate with pembrolizumab was 16.3%, with 1 complete response. The median PFS was 4.8 months and the median OS has not been reached. The 6-month PFS and OS rates were 43.1% and 77.9%, respectively. Treatment remained ongoing in 23 patients.

In addition, the disease control rate was 61.5%. Best overall response was a partial response in 15.4%, CR in 1%, and stable disease in 45.2%. In the responders, the median time to response was 2.1 months. Ninety-four percent of responders were estimated to have a response duration of more than 6 months, and the median duration of response was 8.2 months.

The phase III KEYNOTE-240 is currently assessing pembrolizumab for pretreated patients with HCC, with a primary endpoint of OS.

That's all for today! Thank you for watching OncLive News Network. I'm Gina Columbus.

******************************
 
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