January 17, 2018 : Episode 1

FDA Approvals in PML, NSCLC, and Breast Cancer, Priority Review in DLBCL, and More



FDA approvals in promyelocytic leukemia, lung cancer, and breast cancer, a priority review designation in diffuse large B-cell lymphoma, and encouraging phase III findings in a lung cancer trial.

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

The FDA has approved arsenic trioxide in combination with the all-trans retinoic acid agent tretinoin for the treatment of adults with newly diagnosed low-risk acute promyelocytic leukemia with the t(15;17) translocation or PML-RARA gene expression.

The decision was based on phase III findings and a review of a global safety database for arsenic trioxide. The data showed that arsenic trioxide plus ATRA led to a 2-year event-free survival rate of 97% versus 86% for ATRA plus chemotherapy, for an overall difference of 11%.

In the induction phase of the study, 100% of patients treated in the arsenic trioxide group experienced a hematologic complete remission compared with 95% of those in the comparator arm. The median time to hematologic CR was 32 versus 35 days in the arsenic trioxide and chemotherapy arms, respectively. The rates of differentiation syndrome were also similar between the two groups.

After a median follow-up of 34.4 months, the 2-year overall survival rate was 99% in the arsenic trioxide arm compared with 91% for the chemotherapy group. The 2-year disease-free survival rate was 97% with arsenic trioxide versus 90% in the control arm. The cumulative incidence of relapse at 2 years was 1% versus 6% in the investigational and control arms, respectively.


In breast cancer, the FDA approved olaparib for the treatment of patients with germline BRCA-positive, HER2-negative metastatic disease who have previously received chemotherapy. Additionally, HR-positive patients should have prior endocrine therapy or not be considered appropriate for this type of treatment.

This approval is based on findings from the phase III OlympiAD trial, which showed that the PARP inhibitor reduced the risk of disease progression or death by 42% and improved progression-free survival by 2.8 months versus standard chemotherapy in previously treated patients with BRCA-positive, HER2-negative breast cancer.

Additionally, overall survival was similar between the two groups. A blinded independent central review determined that 100 of the 167 patients who had measurable disease responded to treatment. The response rate was 59.9% in the olaparib arm compared with 28.8% in the standard-therapy group. Investigators observed complete response in 9.0% of the patients who had measurable disease in the olaparib group and in 1.5% in the standard-therapy group.

Treatment selection for olaparib is based on the BRACAnalysis CDx genetic test, which had its FDA approval expanded to include the detection of BRCA mutations in patients with breast cancer.


The FDA has expanded the frontline indication for afatinib to include the treatment of patients with metastatic non-small cell lung cancer whose tumors harbor uncommon EGFR alterations in L861Q, G719X, and/or S768I.

The approval for uncommon, non-resistance EGFR mutations was based on findings from 32 patients in the phase II LUX-Lung 2 trial and the randomized phase III trials known as LUX-Lung 3 and LUX-Lung 6. The confirmed objective response rate with afatinib in these patients was 66%. Of those responding, 52% had duration of response lasting more than 12 months and 33% had response duration of more than 18 months.

The recommended dose from the FDA was 40 mg once daily, which is also the broadly approved dose. For those with renal impairment, the label recommends starting at a dose of 30 mg daily.

Afatinib was initially approved by the FDA in 2013 for the treatment of patients with metastatic NSCLC with exon 19 deletions or exon 21 L858R substitutions. In 2016, this indication was expanded to include patients with squamous histology following progression on a platinum-based chemotherapy.


Also in non-small cell lung cancer, phase III results of the KEYNOTE-189 trial showed that the combination of pembrolizumab with chemotherapy in the frontline setting improved survival in patients with nonsquamous disease.

In the trial, in which patients received frontline pembrolizumab or placebo in combination with pemetrexed and either cisplatin or carboplatin, the study met the coprimary endpoints of improved overall survival and progression-free survival. Full data from the trial will be shared at an upcoming medical meeting.

KEYNOTE-189 is the confirmatory trial for the accelerated approval of pembrolizumab in this setting, which the FDA granted in May 2017. The frontline indication is for patients with metastatic or advanced nonsquamous NSCLC, regardless of PD-L1 expression.

The accelerated approval was based on part 2 of cohort G in the KEYNOTE-021 trial, in which the pembrolizumab triplet elicited an ORR of 55% compared with 29% with chemotherapy alone. The median PFS was 13.0 months with the addition of pembrolizumab versus 8.9 months for chemotherapy.


OncLive is hosting a live webinar focused on issues in the management of early-stage HER2-positive breast cancer on our website on 2 pm Eastern time Friday, January 26.

The broadcast will feature Drs Kimberly L. Blackwell of Duke University School of Medicine, Adam M. Brufsky of University of Pittsburgh, Hope S. Rugo of the Univeristy of California Helen Diller Family Comprehensive Cancer Center, and Lee S. Schwartzberg of West Cancer Center.

To RSVP for the broadcast, please visit onclive.com/webinars/breast2018. There will be a rebroadcast at 12:30 pm January 30, and 1:30 pm January 31, both Eastern time.


This week, we sat down with Dr Thomas Martin of University of California, San Francisco, to discuss the impact of the FDA approval of denosumab in multiple myeloma.

That's all for today.

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

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