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FDA Approval in Hairy Cell Leukemia, NDA in Urothelial Carcinoma, and 2018 ILCA Conference Highlights

Gina Columbus
Published: Friday, Sep 21, 2018



Today-

An FDA approval in hairy cell leukemia, a new drug application in urothelial carcinoma, and updates from the 2018 International Liver Cancer Association Annual Conference.

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

The FDA has approved the CD22-directed recombinant immunotoxin moxetumomab pasudotox, known by the trade name Lumoxiti, for the treatment of adult patients with relapsed or refractory hairy cell leukemia who have received at least 2 prior lines of therapy. This includes treatment with a purine nucleoside analog.

The decision was based on findings from a single-arm, open-label study that included 80 patients with HCL. Data showed that moxetumomab pasudotox induced a complete remission lasting for over 180 days for 30% of patients. Moreover, the objective response rate was 75%.

Overall, 50 patients completed a full 6 cycles of treatment, and patients most commonly discontinued due to CR with minimal residual disease negativity at 15% and adverse events, also at 15%.

The agent was approved with a boxed warning regarding the potential for grade 3/4 capillary leak syndrome and hemolytic uremic syndrome, which occurred in 2.5% and 5% of patients, respectively.

********************************* In urothelial carcinoma, a new drug application has been submitted to the FDA for erdafitinib as a treatment for patients with locally advanced or metastatic disease and FGFR genetic alterations whose tumors progressed following chemotherapy. The application is based on the phase II BLC2001 study in which the oral pan-FGFR tyrosine kinase inhibitor induced a 42% overall response rate in 59 patients with FGFR-positive relapsed/refractory metastatic urothelial carcinoma.

The global trial evaluated ORR in patients with pretreated metastatic or unresectable FGFR alteration–positive urothelial carcinoma who received 1 of 3 doses of erdafitinib. Across all regimens, the ORR was 35% and the confirmed disease control rate was 76%. Median progression-free survival across all dosing cohorts was 5.1 months.

The highest rate of response occurred with continuous dosing of erdafitinib at 8 mg/day, with uptitration to 9 mg/day allowed. In this group of 59 patients, the ORR was 42%, with a complete response in 5% of patients and a partial response in 37%.

Moreover, the DCR in this group was 81%, and the median duration of response was 5.4 months; many responses were ongoing at the time of the analysis. Fifty-seven percent of patients who received 8 mg/day continuous dosing were still alive at 1 year.

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

The 2018 International Liver Cancer Association Annual Conference took place in London last weekend, highlighting the most recent advancements and emerging strategies in hepatocellular carcinoma.

For example, preliminary data of the phase Ib GO30140 study showed that the combination of atezolizumab and bevacizumab demonstrated strong signals of efficacy with a tolerable safety profile as first-line therapy for patients with unresectable or metastatic HCC.

Results showed that the objective response rate was 61% by investigator assessment and 65% by independent review among 23 evaluable patients treated with the combination. All investigator-assessed responses were partial, while there was 1 complete response by independent review.

Responses were also found to be durable, as 10 responses were ongoing for greater than 6 months, including 3 that have continued for more than 1 year after a median follow-up of 10.3 months.

These data follow a breakthrough therapy designation granted by the FDA for this regimen in this patient population in July 2018.

Now, researchers are conducting an expansion phase of the study, in which patients will be randomized to the combination or atezolizumab monotherapy, as well as the phase III IMbrave150 study comparing atezolizumab/bevacizumab with sorafenib in the frontline setting.

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

Also presented at the ILCA meeting was an independent assessment as part of the phase III REFLECT trial, which compared lenvatinib with sorafenib as a first-line therapy for patients with hepatocellular carcinoma.

The initial REFLECT data were the basis for the August 2018 FDA approval of lenvatinib in the frontline setting, as it demonstrated noninferiority to sorafenib.

In the independent assessment, a blinded central panel of about 25 radiology experts assessed the scans according to mRECIST and RECIST v1.1 criteria. These findings showed that progression-free survival and time to progression data produced similar Kaplan-Meier curves for conclusions that clinical investigators reached using mRECIST and that independent imaging review investigators developed using mRECIST and RECIST v1.1 criteria.

However, results diverged when it came to objective response rates, which were 24.1% for lenvatinib and 9.2% for sorafenib per mRECIST. The independent imaging review investigators assessed the ORRs at 40.6% and 12.4% for lenvatinib and sorafenib, respectively, by mRECIST and at 18.8% and 6.5%, respectively, by RECIST v1.1.

Moreover, the major differences in the assessments were in classifying partial responses. Clinical investigators reported PR rates of 23% and 9% for the lenvatinib and sorafenib arms, respectively, by mRECIST. By contrast, independent imaging review investigators found PRs of 38% and 12% for lenvatinib and sorafenib, respectively, by mRECIST, and 18% and 6% by RECIST v1.1.

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

Finally, a 2-year updated analysis of the RESORCE, trial presented at the ILCA conference, demonstrated that regorafenib maintained a prolonged overall survival benefit as second-line therapy for patients with advanced hepatocellular carcinoma.

In the follow-up data, the multikinase inhibitor improved the median OS to 10.7 months compared with 7.9 months with placebo. This translated into a 38% reduction in the risk of death.

Those results were highly similar to findings from the primary analysis, which led to the April 2017 FDA to approval of regorafenib for patients with HCC who have been previously treated with sorafenib.

The updated findings support the validity of analyzing outcomes by patterns of progression. The new data show that patients who developed new extrahepatic lesions during sorafenib therapy had a longer probability of postprogression survival with second-line regorafenib than with placebo.

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

This week, we sat down with Dr Manish Shah, of Weill Cornell Medicine, to discuss improving management in gastric and gastroesophageal junction cancer.

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 hairy cell leukemia, a new drug application in urothelial carcinoma, and updates from the 2018 International Liver Cancer Association Annual Conference.

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

The FDA has approved the CD22-directed recombinant immunotoxin moxetumomab pasudotox, known by the trade name Lumoxiti, for the treatment of adult patients with relapsed or refractory hairy cell leukemia who have received at least 2 prior lines of therapy. This includes treatment with a purine nucleoside analog.

The decision was based on findings from a single-arm, open-label study that included 80 patients with HCL. Data showed that moxetumomab pasudotox induced a complete remission lasting for over 180 days for 30% of patients. Moreover, the objective response rate was 75%.

Overall, 50 patients completed a full 6 cycles of treatment, and patients most commonly discontinued due to CR with minimal residual disease negativity at 15% and adverse events, also at 15%.

The agent was approved with a boxed warning regarding the potential for grade 3/4 capillary leak syndrome and hemolytic uremic syndrome, which occurred in 2.5% and 5% of patients, respectively.

********************************* In urothelial carcinoma, a new drug application has been submitted to the FDA for erdafitinib as a treatment for patients with locally advanced or metastatic disease and FGFR genetic alterations whose tumors progressed following chemotherapy. The application is based on the phase II BLC2001 study in which the oral pan-FGFR tyrosine kinase inhibitor induced a 42% overall response rate in 59 patients with FGFR-positive relapsed/refractory metastatic urothelial carcinoma.

The global trial evaluated ORR in patients with pretreated metastatic or unresectable FGFR alteration–positive urothelial carcinoma who received 1 of 3 doses of erdafitinib. Across all regimens, the ORR was 35% and the confirmed disease control rate was 76%. Median progression-free survival across all dosing cohorts was 5.1 months.

The highest rate of response occurred with continuous dosing of erdafitinib at 8 mg/day, with uptitration to 9 mg/day allowed. In this group of 59 patients, the ORR was 42%, with a complete response in 5% of patients and a partial response in 37%.

Moreover, the DCR in this group was 81%, and the median duration of response was 5.4 months; many responses were ongoing at the time of the analysis. Fifty-seven percent of patients who received 8 mg/day continuous dosing were still alive at 1 year.

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

The 2018 International Liver Cancer Association Annual Conference took place in London last weekend, highlighting the most recent advancements and emerging strategies in hepatocellular carcinoma.

For example, preliminary data of the phase Ib GO30140 study showed that the combination of atezolizumab and bevacizumab demonstrated strong signals of efficacy with a tolerable safety profile as first-line therapy for patients with unresectable or metastatic HCC.

Results showed that the objective response rate was 61% by investigator assessment and 65% by independent review among 23 evaluable patients treated with the combination. All investigator-assessed responses were partial, while there was 1 complete response by independent review.

Responses were also found to be durable, as 10 responses were ongoing for greater than 6 months, including 3 that have continued for more than 1 year after a median follow-up of 10.3 months.

These data follow a breakthrough therapy designation granted by the FDA for this regimen in this patient population in July 2018.

Now, researchers are conducting an expansion phase of the study, in which patients will be randomized to the combination or atezolizumab monotherapy, as well as the phase III IMbrave150 study comparing atezolizumab/bevacizumab with sorafenib in the frontline setting.

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

Also presented at the ILCA meeting was an independent assessment as part of the phase III REFLECT trial, which compared lenvatinib with sorafenib as a first-line therapy for patients with hepatocellular carcinoma.

The initial REFLECT data were the basis for the August 2018 FDA approval of lenvatinib in the frontline setting, as it demonstrated noninferiority to sorafenib.

In the independent assessment, a blinded central panel of about 25 radiology experts assessed the scans according to mRECIST and RECIST v1.1 criteria. These findings showed that progression-free survival and time to progression data produced similar Kaplan-Meier curves for conclusions that clinical investigators reached using mRECIST and that independent imaging review investigators developed using mRECIST and RECIST v1.1 criteria.

However, results diverged when it came to objective response rates, which were 24.1% for lenvatinib and 9.2% for sorafenib per mRECIST. The independent imaging review investigators assessed the ORRs at 40.6% and 12.4% for lenvatinib and sorafenib, respectively, by mRECIST and at 18.8% and 6.5%, respectively, by RECIST v1.1.

Moreover, the major differences in the assessments were in classifying partial responses. Clinical investigators reported PR rates of 23% and 9% for the lenvatinib and sorafenib arms, respectively, by mRECIST. By contrast, independent imaging review investigators found PRs of 38% and 12% for lenvatinib and sorafenib, respectively, by mRECIST, and 18% and 6% by RECIST v1.1.

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

Finally, a 2-year updated analysis of the RESORCE, trial presented at the ILCA conference, demonstrated that regorafenib maintained a prolonged overall survival benefit as second-line therapy for patients with advanced hepatocellular carcinoma.

In the follow-up data, the multikinase inhibitor improved the median OS to 10.7 months compared with 7.9 months with placebo. This translated into a 38% reduction in the risk of death.

Those results were highly similar to findings from the primary analysis, which led to the April 2017 FDA to approval of regorafenib for patients with HCC who have been previously treated with sorafenib.

The updated findings support the validity of analyzing outcomes by patterns of progression. The new data show that patients who developed new extrahepatic lesions during sorafenib therapy had a longer probability of postprogression survival with second-line regorafenib than with placebo.

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

This week, we sat down with Dr Manish Shah, of Weill Cornell Medicine, to discuss improving management in gastric and gastroesophageal junction cancer.

That’s all for today.

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