April 3, 2019 - Episode 1

FDA Approval in Breast Cancer, Review Period Extended in AML, 2019 AACR Highlights, and More


An FDA approval in breast cancer, a review period extended in acute myeloid leukemia, promising findings in a urothelial carcinoma trial, a European approval in non—small cell lung cancer, and highlights from the 2019 AACR Annual Meeting.

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

The FDA has expanded the approval of palbociclib capsules in combination with endocrine therapy for male patients with hormone receptor—positive, HER2-negative advanced or metastatic breast cancer.

The approval is based on real-world data from electronic health records, which demonstrated encouraging response rates with the CDK4/6 inhibitor in combination with an aromatase inhibitor or fulvestrant in this patient population.

Results also showed that the safety profile for men who received palbociclib is consistent with the tolerability in female patients who were treated with the agent. A detailed analysis of these data will be presented at an upcoming medical meeting.

The electronic health records and postmarketing reports that the approval is based on are sourced from the IQVIA Insurance, Flatiron Health Breast Cancer, and the Pfizer global safety databases.

While some therapies are gender-neutral in their indication, others have been indicated only for women, although they are often prescribed for male patients. Current clinical practice standards state that male patients with breast cancer are treated similarly to women with the disease.


In acute myeloid leukemia, the FDA has added 3 months to the review period for a new drug application for quizartinib for the treatment of adult patients with relapsed/refractory FLT3-ITD—positive disease. This will allow the agency to review additional data provided by the manufacturer, Daiichi Sankyo.

The application was filed based on data from the phase III QuANTUM-R study, in which quizartinib reduced the risk of death by 24% versus salvage chemotherapy in patients with FLT3-ITD—positive relapsed/refractory AML after frontline treatment with or without hematopoietic stem cell transplantation.

Results showed that at a median follow-up of 23.5 months, the median OS was 6.2 months with quizartinib compared with 4.7 months with salvage chemotherapy.

The OS benefit was demonstrated across 3 prespecified sensitivity analyses: censoring for the effect of transplant, censoring for the use of other FLT3 inhibitors, and the per-protocol set of patients who were randomized and treated without significant protocol deviations. The survival benefit was also observed across several patient subgroups, such as those who had prior allogeneic HSCT and intermediate and unfavorable risk scores.

The FDA initially granted a priority review designation to the NDA in November 2018, with an action date set for May 25, 2019. Under the new timeframe, the agency is now scheduled to make a final decision on the application by August 25, 2019.


Topline results from the phase II EV-201 trial showed that enfortumab vedotin showed strong clinical activity in patients with locally advanced or metastatic urothelial carcinoma who previously received both platinum-containing chemotherapy and immune checkpoint therapy.

In the single-arm study, enfortumab vedotin induced a 44% objective response rate per independent review. The duration of response was comparable with findings from the phase I EV-101 trial, which supported the breakthrough therapy designation for enfortumab vedotin the FDA granted in March 2018 for the treatment of patients with locally advanced or metastatic urothelial cancer who progressed on a PD-1 or PD-L1 inhibitor.

Results of EV-101 showed that among 71 evaluable patients across the entire cohort, the ORR was 41%, which included 3 complete responses and 26 partial responses.

Seattle Genetics and Astellas, the manufacturers of the agent, plan to present further findings from the trial at an upcoming medical meeting. Based on the EV-201 data, the companies also intend to submit a biologics license application to the FDA by the end of 2019.


In non—small cell lung cancer, the European Commission approved dacomitinib for the frontline treatment of adult patients with locally advanced or metastatic disease with EGFR-activating mutations.

The approval was based on data from the phase III ARCHER 1050 study, which showed that dacomitinib reduced the risk of disease progression or death by more than 40% and resulted in an average 6.5-month improvement in response duration versus gefitinib as a frontline treatment for patients with advanced, EGFR-positive disease.

Results also showed that the median progression-free survival for patients who received dacomitinib was 14.7 months versus 9.2 months for participants who received gefitinib. The median duration of response was 14.8 months with dacomitinib versus 8.3 months with gefitinib.

At a median follow-up of 31.1 months, additional data presented at the 2018 ASCO Annual Meeting showed that the median overall survival was 34.1 months in patients randomized to dacomitinib versus 26.8 months in those randomized to gefitinib.

The FDA approved dacomitinib in September 2018 for the frontline treatment of patients with metastatic NSCLC with EGFR exon 19 deletion or exon 21 L858R substitution mutations, based on the ARCHER 1050 findings.


The 2019 AACR Annual Meeting took place in Atlanta this past week, highlighting therapeutic developments across a wide range of malignancies.

For example, in neuroendocrine carcinoma, results of the phase II DART trial demonstrated that the combination of nivolumab and ipilimumab induced a greater than 40% response rate and was well tolerated in patients with high-grade disease. Additionally, the 6-month progression-free survival rate and median overall survival with the immunotherapy combination were 31% and more than 11 months, respectively. Historically, these rates had been approximately 10% and 3 months, respectively.

Findings of two expansion cohorts of the TATTON trial, which evaluated the combination of osimertinib and the MEK inhibitor savolitinib in patients with EGFR-mutant, MET-amplified non—small cell lung cancer who previously received EGFR TKIs, were also presented at this year’s meeting.

Results demonstrated encouraging clinical activity and an acceptable risk-benefit profile. In the first cohort, which comprised patients who progressed on first- or second-generation EGFR TKIs, the overall response rate was 52%. In the second cohort, which include patients who progressed on a third-generation EGFR TKI, the ORR was 25%.

Finally, results of a small study presented at the conference showed that CAR T cells targeting mesothelin-expressing tumors demonstrated safety and efficacy in a preliminary clinical evaluation in patients with malignant pleural disease.

Data showed that 13 of 21 patients had persistence of CAR T cells in peripheral blood from day 1 to 38 weeks, which was associated with a greater than 50% reduction in mesothelin-related peptide and evidence of tumor regression on imaging.

Objective responses occurred in eight of 11 patients who received a combination of cyclophosphamide conditioning therapy, the CAR T cells, and at least 3 doses of an anti—PD-1 agent. There were also no on-target/off-tumor toxicity, no evidence of immunogenicity, and no severe toxicity.


This week, we sat down with Dr Dipti Gupta, of Memorial Sloan Kettering Cancer, to discuss the cardioprotective role of androgens.

That’s all for today.

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