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FDA Approval in HCC, Breakthrough Designation in MCL, and More

Gina Columbus
Published: Saturday, Jan 19, 2019



Today-

An FDA approval in hepatocellular carcinoma, a breakthrough therapy designation in mantle cell lymphoma, encouraging data in an esophageal cancer trial, disappointing findings in a gastric cancer study, and a European approval in renal cell carcinoma.

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

The FDA has approved cabozantinib as a treatment for patients with hepatocellular carcinoma who previously received sorafenib.

The decision was based on findings from the phase III CELESTIAL trial, in which cabozantinib led to a 2.2-month improvement in overall survival versus placebo. The median OS with cabozantinib was 10.2 months versus 8.0 months for placebo, which represented a 24% reduction in the risk of death.

Additionally, the median progression-free survival was 5.2 months versus 1.9 months for placebo, which was a 56% reduction in the risk of progression or death with the multikinase inhibitor. The objective response rate was 4% with cabozantinib versus 0.4% with placebo. The disease control rate with cabozantinib was 64% compared with 33% for placebo, when including patients with stable disease.

In a subgroup analysis of those who received only prior sorafenib, the median OS was 11.3 months with cabozantinib versus 7.2 months for placebo. The median PFS in this subset was 5.5 months with cabozantinib versus 1.9 months with placebo.

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In mantle cell lymphoma, the FDA has granted the investigational BTK inhibitor zanubrutinib a breakthrough therapy designation for the treatment of adult patients with mantle cell lymphoma who have previously received at least 1 prior therapy.

The designation is based on reported activity with zanubrutinib in MCL, which includes phase II data that were presented at the 2018 ASH Annual Meeting. Results of a single-arm, open-label, multicenter Chinese trial showed that the overall response rate with the agent was 83.5% and responses appeared to be durable. The 1-year progression-free survival rate in patients who received zanubrutinib was 90% and the 2-year PFS was 82%. At a median follow-up of 35.9 weeks, the median PFS had not yet been reached.

These phase II data were also incorporated into a new drug application in China for zanubrutinib in patients with relapsed/refractory disease.

Moreover, updated data of an open-label trial of zanubrutinib in patients with numerous B-cell malignancies, including MCL, showed that the investigator-assessed ORR was 88.9%. Additionally, the median duration of response was 16.2 months and the median PFS for relapsed/refractory patients was 18.0 months.

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The PD-1 inhibitor nivolumab demonstrated a significant extension in overall survival versus chemotherapy in patients with unresectable advanced or recurrent esophageal cancer that is refractory to or intolerant of fluoropyrimidine plus platinum-based therapy, according to topline findings from the phase III ATTRACTION-3 study.

This marks the first checkpoint inhibitor to show a statistically significant extension in OS for patients with PD-L1–unselected, unresectable advanced or recurrent esophageal cancer.

Two-year findings from the open-label phase II ATTRACTION-01/ONO-4538-07 trial were presented at the 2017 ESMO Congress.

Preliminary results demonstrated that the ORR was 17.2% as of May 17, 2015. With the 2-year update, the ORR was 17.2% and the median DOR was 11.7 months. Kaplan-Meier estimates for 1-, 1.5-, and 2-year OS rates were 45.3%, 25.0%, and 17.2%, respectively. Moreover, 1-, 1.5, and 2-year PFS rates were 10.3%, 8.6%, and 8.6%, respectively.

Regarding safety, grade 3/4 adverse events were reported in 29.2% of patients. The most common events were diarrhea, decreased appetite, lung infection, and cough.

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In gastric cancer, frontline varlitinib combined with mFOLFOX6 was not found to significantly reduce tumor size after 12 weeks of therapy versus mFOLFOX6 alone in patients with HER1/HER2 co-expressing advanced or metastatic gastric cancer, missing the primary endpoint of a phase II study.

Results showed that patients who received the small molecule pan-HER inhibitor plus mFOLFOX6 had an average tumor shrinkage of 22.0% after 12 weeks versus 12.5% in those who received mFOLFOX6 alone, which did not reach statistical significance. Following review of 17 progression-free survival events to date, results did show a trend toward an improvement in PFS in the varlitinib arm.

ASLAN Pharmaceuticals, the developer of varlitinib, stated that it will continue to analyze data from this phase II study and work with study investigators to eventually publish the full findings.

The company’s multicenter phase Ib/II trial of varlitinib in combination with gemcitabine and cisplatin in the first-line setting for patients with biliary tract cancer will be presented at the 2019 Gastrointestinal Cancers Symposium.

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

The European Commission has approved the combination of nivolumab and low-dose ipilimumab as a frontline treatment for patients with intermediate- and poor-risk advanced renal cell carcinoma.

The decision was based on data from the phase III CheckMate-214 trial, which demonstrated that the immunotherapy combination led to a 37% reduction in the risk of death versus standard sunitinib in intermediate- and poor-risk patients with advanced RCC, regardless of PD-L1 expression status.

Findings showed that the median OS in intermediate- and poor-risk patients treated with the combination regimen was not yet reached versus 25.9 months for those who received sunitinib. In the overall population, the median OS was not reached with the combination versus 32.9 months with sunitinib.

Moreover, the combination was associated with an ORR of 41.6% versus 26.5% for sunitinib in the intermediate- and poor-risk patient populations. The median duration of response was not yet reached for the combination versus 18.2 months for sunitinib.

However, favorable-risk patients had a significantly higher confirmed ORR with sunitinib versus nivolumab/ipilimumab at 52% versus 29% and a significantly longer PFS. Across the full intent-to-treat population, the ORRs were 39% and 32% in the nivolumab/ipilimumab and sunitinib groups, respectively.

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This week, we sat down with Dr Joseph Sparano, MD, of Albert Einstein College of Medicine, to discuss the future impact of TAILORx on breast cancer management.

That’s all for today.

Thank you for watching OncLive News Network! I’m Gina Columbus.
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Today-

An FDA approval in hepatocellular carcinoma, a breakthrough therapy designation in mantle cell lymphoma, encouraging data in an esophageal cancer trial, disappointing findings in a gastric cancer study, and a European approval in renal cell carcinoma.

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

The FDA has approved cabozantinib as a treatment for patients with hepatocellular carcinoma who previously received sorafenib.

The decision was based on findings from the phase III CELESTIAL trial, in which cabozantinib led to a 2.2-month improvement in overall survival versus placebo. The median OS with cabozantinib was 10.2 months versus 8.0 months for placebo, which represented a 24% reduction in the risk of death.

Additionally, the median progression-free survival was 5.2 months versus 1.9 months for placebo, which was a 56% reduction in the risk of progression or death with the multikinase inhibitor. The objective response rate was 4% with cabozantinib versus 0.4% with placebo. The disease control rate with cabozantinib was 64% compared with 33% for placebo, when including patients with stable disease.

In a subgroup analysis of those who received only prior sorafenib, the median OS was 11.3 months with cabozantinib versus 7.2 months for placebo. The median PFS in this subset was 5.5 months with cabozantinib versus 1.9 months with placebo.

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

In mantle cell lymphoma, the FDA has granted the investigational BTK inhibitor zanubrutinib a breakthrough therapy designation for the treatment of adult patients with mantle cell lymphoma who have previously received at least 1 prior therapy.

The designation is based on reported activity with zanubrutinib in MCL, which includes phase II data that were presented at the 2018 ASH Annual Meeting. Results of a single-arm, open-label, multicenter Chinese trial showed that the overall response rate with the agent was 83.5% and responses appeared to be durable. The 1-year progression-free survival rate in patients who received zanubrutinib was 90% and the 2-year PFS was 82%. At a median follow-up of 35.9 weeks, the median PFS had not yet been reached.

These phase II data were also incorporated into a new drug application in China for zanubrutinib in patients with relapsed/refractory disease.

Moreover, updated data of an open-label trial of zanubrutinib in patients with numerous B-cell malignancies, including MCL, showed that the investigator-assessed ORR was 88.9%. Additionally, the median duration of response was 16.2 months and the median PFS for relapsed/refractory patients was 18.0 months.

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

The PD-1 inhibitor nivolumab demonstrated a significant extension in overall survival versus chemotherapy in patients with unresectable advanced or recurrent esophageal cancer that is refractory to or intolerant of fluoropyrimidine plus platinum-based therapy, according to topline findings from the phase III ATTRACTION-3 study.

This marks the first checkpoint inhibitor to show a statistically significant extension in OS for patients with PD-L1–unselected, unresectable advanced or recurrent esophageal cancer.

Two-year findings from the open-label phase II ATTRACTION-01/ONO-4538-07 trial were presented at the 2017 ESMO Congress.

Preliminary results demonstrated that the ORR was 17.2% as of May 17, 2015. With the 2-year update, the ORR was 17.2% and the median DOR was 11.7 months. Kaplan-Meier estimates for 1-, 1.5-, and 2-year OS rates were 45.3%, 25.0%, and 17.2%, respectively. Moreover, 1-, 1.5, and 2-year PFS rates were 10.3%, 8.6%, and 8.6%, respectively.

Regarding safety, grade 3/4 adverse events were reported in 29.2% of patients. The most common events were diarrhea, decreased appetite, lung infection, and cough.

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

In gastric cancer, frontline varlitinib combined with mFOLFOX6 was not found to significantly reduce tumor size after 12 weeks of therapy versus mFOLFOX6 alone in patients with HER1/HER2 co-expressing advanced or metastatic gastric cancer, missing the primary endpoint of a phase II study.

Results showed that patients who received the small molecule pan-HER inhibitor plus mFOLFOX6 had an average tumor shrinkage of 22.0% after 12 weeks versus 12.5% in those who received mFOLFOX6 alone, which did not reach statistical significance. Following review of 17 progression-free survival events to date, results did show a trend toward an improvement in PFS in the varlitinib arm.

ASLAN Pharmaceuticals, the developer of varlitinib, stated that it will continue to analyze data from this phase II study and work with study investigators to eventually publish the full findings.

The company’s multicenter phase Ib/II trial of varlitinib in combination with gemcitabine and cisplatin in the first-line setting for patients with biliary tract cancer will be presented at the 2019 Gastrointestinal Cancers Symposium.

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

The European Commission has approved the combination of nivolumab and low-dose ipilimumab as a frontline treatment for patients with intermediate- and poor-risk advanced renal cell carcinoma.

The decision was based on data from the phase III CheckMate-214 trial, which demonstrated that the immunotherapy combination led to a 37% reduction in the risk of death versus standard sunitinib in intermediate- and poor-risk patients with advanced RCC, regardless of PD-L1 expression status.

Findings showed that the median OS in intermediate- and poor-risk patients treated with the combination regimen was not yet reached versus 25.9 months for those who received sunitinib. In the overall population, the median OS was not reached with the combination versus 32.9 months with sunitinib.

Moreover, the combination was associated with an ORR of 41.6% versus 26.5% for sunitinib in the intermediate- and poor-risk patient populations. The median duration of response was not yet reached for the combination versus 18.2 months for sunitinib.

However, favorable-risk patients had a significantly higher confirmed ORR with sunitinib versus nivolumab/ipilimumab at 52% versus 29% and a significantly longer PFS. Across the full intent-to-treat population, the ORRs were 39% and 32% in the nivolumab/ipilimumab and sunitinib groups, respectively.

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

This week, we sat down with Dr Joseph Sparano, MD, of Albert Einstein College of Medicine, to discuss the future impact of TAILORx on breast cancer management.

That’s all for today.

Thank you for watching OncLive News Network! I’m Gina Columbus.
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Online CME Activities
TitleExpiration DateCME Credits
Archived Version of a Live Webcast: Virtual Current Trends™: European Perspectives on the Advancing Role of CAR T-Cell Therapy in Hematologic MalignanciesJun 29, 20192.0
Community Practice Connections™: Practical Application of Sequencing for EGFR-Mutant Lung Cancers: A Focus on Recent Evidence and Key Next Steps in TrialsJun 29, 20192.5
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