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FDA Approvals in Urothelial Cancer and Prostate Cancer, Priority Review in CRC, and More
Today-
FDA approvals in urothelial cancer and prostate cancer, priority review designations in colorectal cancer and urothelial cancer, breakthrough designations in breast cancer and myelodysplastic syndromes, and ODAC hearing decisions in sarcoma, pancreatic cancer, and bladder cancer.
Welcome to OncLive News Network! I'm Gina Columbus.
The FDA has granted an accelerated approval to enfortumab vedotin-ejfv, known by the trade name Padcev, for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have received prior treatment with a PD-1/PD-L1 inhibitor and platinum-containing chemotherapy.
The approval is based on data from the first cohort of patients in the phase II EV-201 trial, which showed that enfortumab vedotin elicited a 44% overall response rate in patients with locally advanced or metastatic urothelial cancer, which included a 12% complete response rate and a 32% partial response rate. Responses were observed across all subgroups, regardless of response to prior PD-1/PD-L1 inhibitors or presence of liver metastases.
Additional results showed that the median overall survival was 11.7 months, the median progression-free survival was 5.8 months, and the median duration of response was 7.6 months. The approval is contingent on the results of a confirmatory trial.
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The FDA has approved enzalutamide for the treatment of patients with metastatic castration-sensitive prostate cancer.
The approval is based on findings from the phase III ARCHES trial, in which the median radiographic progression-free survival in men with this type of prostate cancer was not reached with enzalutamide plus androgen deprivation therapy and was 19.45 months with placebo and ADT, which led to a 61% reduction in the risk of radiographic progression or death with enzalutamide.
Enzalutamide plus ADT was also linked with a reduction in the risk of time to prostate-specific antigen progression by 81% and the time to initiation of new antineoplastic therapy by 72% versus ADT alone.
An interim OS analysis showed that the median OS has not been reached in either arm, and OS data were not mature at the time of the final rPFS analysis.
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In colorectal cancer, the FDA has granted a priority review designation to a supplemental new drug application for the combination of encorafenib and cetuximab as a treatment for patients with advanced BRAF V600E—mutant disease following up to 2 prior lines of therapy.
The designation is based on findings from the phase III BEACON CRC study, which evaluated encorafenib plus cetuximab with or without binimetinib in this patient population.
Patients treated with the combination of encorafenib and cetuximab demonstrated a statistically significant improvement in ORR per blinded independent central review at 20.4% versus 1.9%. The median OS was also improved with the doublet compared with the control arm at 8.4 months and 5.4 months, respectively.
The FDA will make a decision on the sNDA in April 2020.
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The FDA has granted a priority review designation to a new drug application for UGN-101, also known as mitomycin gel, for the treatment of patients with low-grade, upper tract urothelial cancer.
UGN-101 uses the RTGel technology platform and is designed to permit longer exposure of mitomycin to urinary tract tissue, which allows for the nonsurgical treatment of these tumors.
The designation is based on results from the pivotal phase III OLYMPUS trial, in which a final analysis showed that UGN-101 elicited a complete response rate of 59% in this patient population.
The FDA must make a decision on the application by April 18, 2020.
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In breast cancer, the FDA has granted tucatinib a breakthrough therapy designation for use in combination with trastuzumab and capecitabine for the treatment of patients with unresectable locally advanced or metastatic HER2-positive disease, including those with brain metastases, who had prior trastuzumab, pertuzumab, and ado-trastuzumab emtansine.
The designation is based on data from the phase II HER2CLIMB trial, results of which showed that the tucatinib triplet reduced the risk of death by 34% versus trastuzumab and capecitabine alone in this patient population.
The median overall survival was 21.9 months with the tucatinib triplet compared with 17.4 months with trastuzumab and capecitabine alone. The 1- and 2-year overall survival rates were 76% versus 62% and 45% versus 27% in the tucatinib and control arms, respectively. The OS benefit was upheld across all prespecified subgroups.
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The FDA has granted a breakthrough therapy designation to ivosidenib for the treatment of adult patients with relapsed/refractory myelodysplastic syndromes who harbor IDH1 mutations.
The designation is based on findings from an MDS substudy of a phase I trial evaluating ivosidenib in patients with advanced hematologic malignancies who have IDH1 mutations. In the MDS cohort, data showed an overall response rate of 75%, which included a 42% complete response rate with ivosidenib in this patient population. The median duration of CR had not been reached, and of patients who achieved a CR, 60% were relapse-free at 1 year.
Results of the MDS substudy also showed that single-agent ivosidenib was well tolerated and associated with durable remissions.
The FDA's Oncologic Drugs Advisory Committee voted unanimously 11 to 0 in favor of approving tazemetostat tablets as a treatment for patients with metastatic or locally advanced epithelioid sarcoma that is ineligible for curative surgery.
The purpose of the hearing was to discuss data supporting a new drug application for an accelerated approval of tazemetostat in this setting, and to determine whether the overall response rate benefit with the EZH2 inhibitor was enough to warrant an indication and that it outweighed the risks of secondary malignancies.
The FDA granted a priority review designation to the NDA for tazemetostat in July 2019 for this indication. The application is primarily based on findings from a cohort of patients with epithelioid sarcoma in an ongoing, single-arm, phase II study, which showed that the ORR was 15%, comprised of 8 partial responses and 1 complete response.
The FDA, which is not required to follow ODAC, is expected to make a decision on the approval by January 23, 2020.
In pancreatic cancer, the FDA's Oncologic Drugs Advisory Committee voted 7 to 5 in favor of olaparib tablets for an indication as a maintenance treatment of adult patients with deleterious or suspected deleterious BRCA-mutant metastatic disease whose disease has not progressed on frontline platinum-based chemotherapy.
The FDA scheduled the hearing to discuss a supplemental new drug application for olaparib in this setting, which was based on results from the phase III POLO trial. Findings showed a progression-free survival benefit with olaparib versus placebo in this patient population.
The median PFS with the PARP inhibitor was 7.4 months compared with 3.8 months with placebo. In addition, after 2 years, 22.1% of patients had no disease progression versus 9.6% of those who received placebo.
The FDA's Oncologic Drugs Advisory Committee voted 9 to 4 supporting the approval of a new drug application for pembrolizumab for the treatment of patients with Bacillus Calmette-Guerin—unresponsive, high-risk, non-muscle invasive bladder cancer with carcinoma in-situ with or without papillary tumors who are ineligible for or chose to not undergo cystectomy.
The application is based on findings from the phase II KEYNOTE-057 trial. An FDA analysis of 97 patients from the trial found that pembrolizumab elicited a 41.2% complete response rate and a median duration of CR of 16.2 months in this patient population. Nineteen of the 40 responding patients maintained their response for at least 1 year.
The panel was voting that the response efficacy data compared with the toxicity findings from the KEYNOTE-057 trial demonstrate a favorable risk/benefit profile for pembrolizumab in this setting. The FDA previously granted a priority review designation to the pembrolizumab NDA with an action date scheduled for January 2020.
This week, we sat down Dr Andrew Zhu of Massachusetts General Hospital and Dr Nikolaos Pyrsopoulos to discuss frontline immunotherapy in hepatocellular carcinoma.
That's all for today.
Thank you for watching OncLive News Network! I'm Gina Columbus.
