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FDA Approvals in Bladder Cancer and NSCLC, and 2019 ELCC Highlights

Gina Columbus
Published: Friday, Apr 19, 2019



Today-

FDA approvals in bladder cancer and non–small cell lung cancer, and highlights from the European Lung Cancer Congress.

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

The FDA has granted an accelerated approval to erdafitinib, known by the trade name Balversa, for the treatment of adult patients with locally advanced or metastatic bladder cancer with an FGFR3 or FGFR2 alteration that has progressed on platinum-containing chemotherapy.

This marks the first targeted therapy approval in metastatic bladder cancer.

The decision is based on findings from the phase II BLC2001 trial, in which erdafitinib led to an overall response rate of 32.2% in patients with FGFR2/FGFR3-positive locally advanced or metastatic bladder cancer. The ORR comprised a complete response rate of 2.3% and a partial response rate of 29.9%, and responders included patients who had been unresponsive to PD-1/PD-L1 inhibition.

Moreover, the agency noted that a companion diagnostic device approved by the agency should be used in patient selection for erdafitinib. The QIAGEN therascreen FGFR RGQ Reverse-transcription-polymerase chain reaction Kit was simultaneously approved as a companion diagnostic for use with erdafitinib.

The accelerated approval of erdafitinib in bladder cancer is contingent on the results of a confirmatory trial.

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

In non–small cell lung cancer, the FDA expanded the frontline approval of single-agent pembrolizumab beyond the metastatic setting to now also include patients with stage III disease who are ineligible for surgery or definitive chemoradiation, and whose tumors do not harbor EGFR or ALK aberrations. The FDA also lowered the PD-L1 eligibility threshold to an expression level of 1% or higher.

The approval is based on findings from the phase III KEYNOTE-042 trial, which showed that frontline pembrolizumab led to a median overall survival of 16.7 months versus 12.1 months with chemotherapy in patients with advanced or metastatic NSCLC and a tumor proportion score of at least 1%. In an exploratory analysis that examined all patients with PD-L1 TPS of 1% to 49%, the median OS was 13.4 months and 12.1 months with pembrolizumab and chemotherapy, respectively.

Results showed that OS did correlate with greater levels of PD-L1 expression. While median progression-free survival with pembrolizumab was higher in patients with TPS greater than 50% at 7.1 months compared with 6.4 months with chemotherapy, it was lower in the TPS greater than 1% group, at 5.4 months with pembrolizumab and 6.5 months with chemotherapy.

Moreover, the FDA also expanded the approval of the PD-L1 IHC 22C3 pharmDX assay, allowing the test to be used as a companion diagnostic to identify more patients with stage III or metastatic NSCLC who can undergo first-line treatment with pembrolizumab.

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

The European Lung Cancer Congress took place this past week in Geneva, Switzerland, showcasing the latest clinical trials in the field of lung cancer.

For example, an exploratory analysis from the phase III IMpower150 trial that was presented showed that the 4-drug regimen of atezolizumab, bevacizumab, carboplatin, and paclitaxel, has emerged as a potential new standard of care for patients with EGFR-positive metastatic nonsquamous non–small cell lung cancer who have failed on TKI treatment.

The data showed that the regimen reduced the risk of death by 39% compared with the triplet of bevacizumab, carboplatin, and paclitaxel. The median OS was not yet reached with ABCP compared with 18.7 months with BCP.

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

Results of the CheckMate-451 trial, which evaluated nivolumab alone or in combination with ipilimumab compared with placebo as a maintenance therapy in extensive-stage small cell lung cancer, were also presented at this year’s meeting.

Data showed that there was no overall survival advantage with nivolumab monotherapy or plus ipilimumab. Moreover, only the subgroup of patients aged younger than 65 years demonstrated OS that favored the combination over placebo at 10.2 versus 8.9 months, respectively. In responding patients, the duration of response during maintenance therapy was 10 months with the combination, 11 months for nivolumab alone, and 8 months for placebo.

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

Moreover, final results from 2 phase I expansion cohorts of frontline osimertinib presented at the meeting confirmed the efficacy of the third-generation TKI in patients with EGFR-positive non¬–small cell lung cancer.

At a median follow-up of 19.1 months, the expansion cohort data from the phase I AURA trial showed that the objective response rate was 67% in patients receiving osimertinib at an 80-mg dose, and it was 87% in patients receiving an elevated dose of 160 mg of osimertinib. The ORR was 77% in the overall patient cohort with both doses.

The median best percentage change overall in target lesion size was -48%, the median change in the low-dose cohort was -46%, and the median change was -59% in the higher dose cohort. Additionally, at 78% data maturity, the median PFS in the 80 mg, 160 mg, and overall cohorts was 22.1 months, 19.3 months, and 20.5 months, respectively.

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

Finally, an exploratory analysis of the phase III MYSTIC trial showed that the initial overall survival analysis of the study of first-line durvalumab alone or in combination with tremelimumab versus platinum-based chemotherapy in patients with metastatic non–small cell lung cancer may have been confounded by high rates of post-study immunotherapy given in the control arm.

Post-study immunotherapy was administered to more patients receiving chemotherapy than durvalumab, and more patients in the chemotherapy arm also received treatment other than the study drug. As of October 4, 2018, subsequent treatment had been administered to 73 patients in the durvalumab arm compared with 95 patients in the chemotherapy arm within 2 months of discontinuing treatment.

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

This week, we sat down with Dr Steven Treon of Harvard Medical School to discuss BTK combination strategies for B-cell malignancies.

That’s all for today.

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

FDA approvals in bladder cancer and non–small cell lung cancer, and highlights from the European Lung Cancer Congress.

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

The FDA has granted an accelerated approval to erdafitinib, known by the trade name Balversa, for the treatment of adult patients with locally advanced or metastatic bladder cancer with an FGFR3 or FGFR2 alteration that has progressed on platinum-containing chemotherapy.

This marks the first targeted therapy approval in metastatic bladder cancer.

The decision is based on findings from the phase II BLC2001 trial, in which erdafitinib led to an overall response rate of 32.2% in patients with FGFR2/FGFR3-positive locally advanced or metastatic bladder cancer. The ORR comprised a complete response rate of 2.3% and a partial response rate of 29.9%, and responders included patients who had been unresponsive to PD-1/PD-L1 inhibition.

Moreover, the agency noted that a companion diagnostic device approved by the agency should be used in patient selection for erdafitinib. The QIAGEN therascreen FGFR RGQ Reverse-transcription-polymerase chain reaction Kit was simultaneously approved as a companion diagnostic for use with erdafitinib.

The accelerated approval of erdafitinib in bladder cancer is contingent on the results of a confirmatory trial.

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

In non–small cell lung cancer, the FDA expanded the frontline approval of single-agent pembrolizumab beyond the metastatic setting to now also include patients with stage III disease who are ineligible for surgery or definitive chemoradiation, and whose tumors do not harbor EGFR or ALK aberrations. The FDA also lowered the PD-L1 eligibility threshold to an expression level of 1% or higher.

The approval is based on findings from the phase III KEYNOTE-042 trial, which showed that frontline pembrolizumab led to a median overall survival of 16.7 months versus 12.1 months with chemotherapy in patients with advanced or metastatic NSCLC and a tumor proportion score of at least 1%. In an exploratory analysis that examined all patients with PD-L1 TPS of 1% to 49%, the median OS was 13.4 months and 12.1 months with pembrolizumab and chemotherapy, respectively.

Results showed that OS did correlate with greater levels of PD-L1 expression. While median progression-free survival with pembrolizumab was higher in patients with TPS greater than 50% at 7.1 months compared with 6.4 months with chemotherapy, it was lower in the TPS greater than 1% group, at 5.4 months with pembrolizumab and 6.5 months with chemotherapy.

Moreover, the FDA also expanded the approval of the PD-L1 IHC 22C3 pharmDX assay, allowing the test to be used as a companion diagnostic to identify more patients with stage III or metastatic NSCLC who can undergo first-line treatment with pembrolizumab.

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

The European Lung Cancer Congress took place this past week in Geneva, Switzerland, showcasing the latest clinical trials in the field of lung cancer.

For example, an exploratory analysis from the phase III IMpower150 trial that was presented showed that the 4-drug regimen of atezolizumab, bevacizumab, carboplatin, and paclitaxel, has emerged as a potential new standard of care for patients with EGFR-positive metastatic nonsquamous non–small cell lung cancer who have failed on TKI treatment.

The data showed that the regimen reduced the risk of death by 39% compared with the triplet of bevacizumab, carboplatin, and paclitaxel. The median OS was not yet reached with ABCP compared with 18.7 months with BCP.

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

Results of the CheckMate-451 trial, which evaluated nivolumab alone or in combination with ipilimumab compared with placebo as a maintenance therapy in extensive-stage small cell lung cancer, were also presented at this year’s meeting.

Data showed that there was no overall survival advantage with nivolumab monotherapy or plus ipilimumab. Moreover, only the subgroup of patients aged younger than 65 years demonstrated OS that favored the combination over placebo at 10.2 versus 8.9 months, respectively. In responding patients, the duration of response during maintenance therapy was 10 months with the combination, 11 months for nivolumab alone, and 8 months for placebo.

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

Moreover, final results from 2 phase I expansion cohorts of frontline osimertinib presented at the meeting confirmed the efficacy of the third-generation TKI in patients with EGFR-positive non¬–small cell lung cancer.

At a median follow-up of 19.1 months, the expansion cohort data from the phase I AURA trial showed that the objective response rate was 67% in patients receiving osimertinib at an 80-mg dose, and it was 87% in patients receiving an elevated dose of 160 mg of osimertinib. The ORR was 77% in the overall patient cohort with both doses.

The median best percentage change overall in target lesion size was -48%, the median change in the low-dose cohort was -46%, and the median change was -59% in the higher dose cohort. Additionally, at 78% data maturity, the median PFS in the 80 mg, 160 mg, and overall cohorts was 22.1 months, 19.3 months, and 20.5 months, respectively.

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

Finally, an exploratory analysis of the phase III MYSTIC trial showed that the initial overall survival analysis of the study of first-line durvalumab alone or in combination with tremelimumab versus platinum-based chemotherapy in patients with metastatic non–small cell lung cancer may have been confounded by high rates of post-study immunotherapy given in the control arm.

Post-study immunotherapy was administered to more patients receiving chemotherapy than durvalumab, and more patients in the chemotherapy arm also received treatment other than the study drug. As of October 4, 2018, subsequent treatment had been administered to 73 patients in the durvalumab arm compared with 95 patients in the chemotherapy arm within 2 months of discontinuing treatment.

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

This week, we sat down with Dr Steven Treon of Harvard Medical School to discuss BTK combination strategies for B-cell malignancies.

That’s all for today.

Thank you for watching OncLive News Network! I’m Gina Columbus.
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Community Practice Connections™: 22nd Annual International Congress on Hematologic Malignancies®: Focus on Leukemias, Lymphomas and MyelomaMay 30, 20192.0
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