publication date: Jan. 25, 2019

FDA approves 19 new cancer drugs and biologics in 2018—and don’t forget two new endpoints and “real-time” review

By Claire Dietz and Matthew Bin Han Ong

Last year, FDA approved 19 applications for new cancer drug and biologics as well as 38 supplemental indications and four biosimilars, agency officials said. 

“These advances in anticancer therapy included a landmark approval of the first histology-agnostic, biomarker-defined new molecular entity and approvals based on real-time data review and novel end points,” Gideon Blumenthal, acting deputy director of FDA’s Office of Hematology and Oncology Products and Richard Pazdur, director of the Oncology Center of Excellence at FDA, wrote in a Jan. 22 commentary published in Nature Reviews.

Overall, in 2018, FDA approved 59 novel drugs, breaking its record of 53 drugs in 1996—with the largest share of approvals being in oncology.

In one of the highlights in cancer, in November 2018, the agency approved larotrectinib, the first ever oral tyrosine kinase inhibitor for the treatment of adult and pediatric patients with solid tumors that have a neurotrophic receptor tyrosine kinase gene fusion without a known acquired resistance mutation (The Cancer Letter, Nov. 11, 2018).

“If you look at the rank-and-file signaling stuff, all these things in the RTK pathway, the NCI intramural scientists had been a big part of that,” NCI Director Ned Sharpless said to The Cancer Letter. “Obviously, just getting back from the University of Pennsylvania and spending time with Carl June, you know, CAR-T cells, they were freaking science fiction like three years ago. It’s unbelievable.

“That’s going to change oncology and those things were certainly really heavily supported extramurally and intramurally by the NCI. It’s just remarkable and that doesn’t happen by accident and that certainly doesn’t happen solely by industry.”

Also, FDA has developed two new endpoints:

  • Metastasis-free survival, a prolonged delay in the development of metastatic disease as an objective and clinically relevant outcome (The Cancer Letter, July 20, 2018). The MFS endpoint was used to approve apalutamide and enzalutamide.

  • Minimal residual disease, for the approval of blinatumomab for B cell-precursor acute lymphoblastic leukemia (The Cancer Letter, March 9, 2018).

Blinatomumab was indicated for adult and pediatric patients “who were in first or second complete remission with minimal residual disease ≥0.1% on the basis of the MRD response rate—that is, the achievement of undetectable MRD after one cycle of treatment using a test with a sensitivity of 0.01%,” Blumenthal and Pazdur wrote.

FDA has approved several agents using Real-Time Oncology Review, a pilot review program. In November, the agency expanded the approved use of Adcetris (brentuximab vedotin) injection in combination with chemotherapy for adult patients with certain types or peripheral T-cell lymphoma (The Cancer Letter, Nov. 16, 2018).

In the commentary, Blumenthal and Pazdur listed a number of significant approvals, including many molecularly targeted therapies:

  • Novel small-molecule tropomyosin receptor kinase inhibitor larotrectinib, for treatment of pediatric/adult patients with unresectable or metastatic NTRK gene fusion-positive solid tumors, irrespective of tumor histology. In the main study, the confirmed ORR in 55 patients was at 75%, and 39% of responses lasted for at least a year

  • 12 tumor types were represented, from non-small cell lung cancer to infantile fibrosarcoma

  • Talazoparib and olaparib, for metastatic breast cancer with deleterious germline BRCA mutations

  • Lorlatinib, for metastatic, ALK-rearranged NSCLC

  • Dacomitinib, afatinib, and osimertinib, for metastatic NSCLC with EGFR aberrations

  • Encorafenib plus binimetinib, for advanced-stage BRAFV600E/K; and dabrafenib plus trametinib for the adjuvant treatment of BRAFV600E/K-mutant melanoma

  • Gilteritinib or ivosidenib monotherapy for patients with relapsed and/or refractory FLT3-mutant or IDH1-mutant AML

  • Glasdegib or venetoclax in combination with low-dose cytarabine, for patients with newly diagnosed AML 75 years and over who have co-morbidities precluding intensive chemotherapy

  • Apalutamide and enzalutamide, metastatic free survival in non-metastatic castration-resistant prostate cancer

  • Blinatumomab, for adult/pediatric patients with B cell-precursor acute lymphoblastic leukemia in first or second remission with minimal residual disease

  • ClonoSEQ, a next-generation sequencing assay, for the detection and monitoring of MRD in patients with ALL or multiple myeloma

  • Label expansion for tisagenlecleucel, a chimeric antigen receptor T cell product, to include some patients with relapsed/refractory large B cell lymphoma

  • Cemiplimab-rwlc, a PD-1 antibody, for advanced-stage cutaneous squamous cell cancer

  • Label expansions for several anti-PD-1 or anti-PD-L1 antibodies, as monotherapies or in combination with chemotherapy or anti-cytotoxic T lymphocyte antigen 4 (CTLA-4)

  • Label restrictions for pembrolizumab and atezolizumab, in the initial treatment of advanced-stage cisplatin-ineligible patients with PD-L1-positive tumors according to FDA-approved companion diagnostics or those ineligible for any platinum-containing chemotherapy (regardless of PD-L1 expression).

A list of cancer indications approved in 2018 follows.

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