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FDA Actions & Updates

The latest approvals, designations, and new indications from the U.S. Food and Drug Administration for oncology drugs.

Monday, January 27, 2020

The FDA granted accelerated approval to tazemetostat for adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection.

Efficacy was investigated in a single-arm cohort (Cohort 5) of a multi-center trial (Study EZH-202, NCT02601950) in patients with histologically confirmed, metastatic or locally advanced epithelioid sarcoma. Patients were required to have INI1 loss, detected using local tests, and an Eastern Cooperative Oncology Group performance status of 0-2. Patients received tazemetostat 800 mg orally twice daily until disease progression or unacceptable toxicity. The major efficacy outcome measures were confirmed overall response rate (ORR) according to RECIST v1.1 (assessed by blinded independent central review) and duration of response.

The ORR for the 62 patients in Cohort 5 was 15 percent (95% CI: 7%, 26%), with 1.6 percent having complete responses and 13 percent partial responses; 67 percent of those responding had responses lasting 6 months or longer.

The most common adverse reactions (incidence ≥20%) were pain, fatigue. nausea, decreased appetite, vomiting and constipation.

The recommended tazemetostat dose is 800 mg taken orally twice daily with or without food.


Friday, January 10, 2020

The FDA approved avapritinib for adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including D842V mutations.

Avapritinib is the first therapy approved for patients with GIST harboring a PDGFRA exon 18 mutation.

Efficacy was investigated in NAVIGATOR (NCT02508532), a multi-center, single-arm, open-label trial enrolling 43 patients with GIST harboring a PDGFRA exon 18 mutation, including 38 patients with PDGFRA D842V mutations. The trial initially enrolled patients at a starting dose of 400 mg orally once daily, which was later reduced to the recommended dose of 300 mg orally once daily due to toxicity. Patients received avapritinib until disease progression or unacceptable toxicity. The major efficacy outcome measure was overall response rate (ORR) based on disease assessment by independent radiological review using modified RECIST 1.1 criteria. An additional efficacy outcome measure was response duration.

For patients harboring a PDGFRA exon 18 mutation, the ORR was 84 percent (95% CI: 69%, 93%), with 7 percent complete responses and 77 percent partial responses. For the subgroup of patients with PDGFRA D842V mutations, the ORR was 89 percent (95% CI: 75%, 97%), with 8 percent complete responses and 82% partial responses. The median response duration was not reached with a median duration of follow-up for all patients of 10.6 months (range 0.3 to 24.9 months); 61 percent of the responding patients with exon 18 mutations had a response lasting 6 months or longer (31% of patients with an ongoing response were followed for less than 6 months).

The most common adverse reactions (incidence ≥ 20%) in patients who received avapritinib were edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increased lacrimation, abdominal pain, constipation, rash and dizziness.

The recommended avapritinib dose is 300 mg orally once daily on an empty stomach, at least one hour before and two hours after a meal.


Wednesday, January 8, 2020

The FDA approved pembrolizumab for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy. 

Efficacy was investigated in KEYNOTE-057 (NCT, a multicenter, single-arm trial that enrolled 148 patients with high-risk NMIBC, 96 of whom had BCG-unresponsive CIS with or without papillary tumors. Patients received pembrolizumab 200 mg every 3 weeks until unacceptable toxicity, persistent or recurrent high-risk NMIBC or progressive disease, or up to 24 months of therapy without disease progression.

The major efficacy outcome measures were complete response (as defined by negative results for cystoscopy [with TURBT/biopsies as applicable], urine cytology, and computed tomography urography [CTU] imaging) and duration of response. The complete response rate in the 96 patients with high-risk BCG-unresponsive NMIBC with CIS was 41 percent (95% CI: 31, 51) and median response duration was 16.2 months (0.0+, 30.4+). Forty-six percent (46%) of responding patients experienced a complete response lasting at least 12 months.

The most common adverse reactions (incidence ≥10%) in patients who received pembrolizumab in KEYNOTE-057 were fatigue, diarrhea, rash, pruritis, musculoskeletal pain, hematuria, cough, arthralgia, nausea, constipation, urinary tract infection, peripheral edema, hypothyroidism, and nasopharyngitis 

The recommended pembrolizumab dose is 200 mg every 3 weeks.


Monday, January 6, 2020

The FDA granted accelerated approval to fam-trastuzumab deruxtecan-nxki for patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.

Efficacy was investigated in DESTINY-Breast01 (NCT03248492), a multicenter, single-arm trial enrolling 184 female patients with HER2-positive, unresectable and/or metastatic breast cancer who had received two or more prior anti-HER2 therapies. Patients received fam-trastuzumab deruxtecan-nxki 5.4 mg/kg by intravenous infusion every 3 weeks until unacceptable toxicity or disease progression.

The main efficacy outcome measures were confirmed objective response rate (ORR) assessed by independent central review using RECIST 1.1 and response duration. ORR was 60.3 percent (95% CI: 52.9, 67.4), with a 4.3 percent complete response rate and a 56 percent partial response rate. Median response duration was 14.8 months (95% CI: 13.8, 16.9).

The safety was evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of fam-trastuzumab deruxtecan-nxki 5.4 mg/kg in DESTINY-Breast01 and Study DS8201-A-J101 (NCT02564900). The most common adverse reactions (frequency ≥20%) to fam-trastuzumab deruxtecan-nxki were nausea, fatigue, vomiting, alopecia, constipation, decreased appetite, anemia, neutropenia, diarrhea, leukopenia, cough, and thrombocytopenia. The prescribing information includes a Boxed Warning to advise health professionals of the risk of interstitial lung disease (ILD) and embryo-fetal toxicity. Fatal outcomes due to ILD occurred in 2.6 percent of patients.

The recommended fam-trastuzumab deruxtecan-nxki dose is 5.4 mg/kg given as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.


Monday, January 6, 2020

The FDA approved olaparib for the maintenance treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) metastatic pancreatic adenocarcinoma, as detected by an FDA-approved test, whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen.

The FDA also approved the BRACAnalysis CDx test as a companion diagnostic for the selection of patients with pancreatic cancer for treatment with olaparib based upon the identification of deleterious or suspected deleterious germline mutations in BRCA1 or BRCA2 genes.

Efficacy was investigated in POLO (NCT02184195), a double-blind, placebo-controlled, multi-center trial that randomized (3:2) 154 patients with gBRCAm metastatic pancreatic adenocarcinoma to olaparib 300 mg orally twice daily or placebo until disease progression or unacceptable toxicity.

The main efficacy outcome measure was progression-free survival (PFS) by blinded independent central review using RECIST 1.1. Additional efficacy outcome measures were overall survival (OS) and overall response rate (ORR).

Median PFS was 7.4 months (95% CI: 4.1, 11.0) for patients who received olaparib compared with 3.8 months (95% CI: 3.5, 4.9) for patients who received placebo (HR 0.53; 95% CI: 0.35, 0.81; p=0.0035). Median OS for olaparib and placebo was 18.9 months (95% CI: 14.9, 26.2) and 18.1 months (95% CI: 12.6, 26.1), respectively (HR 0.91; 95% CI: 0.56, 1.46; p=0.683); ORR among patients who had measurable disease at baseline was 23 percent and 12 percent, respectively.

In general, the adverse reaction profile of olaparib observed in POLO is consistent with the known safety profile of olaparib. The most common adverse reactions to olaparib (≥10%) in clinical trials include nausea, fatigue, vomiting, abdominal pain, anemia, diarrhea, dizziness, neutropenia, leukopenia, nasopharyngitis/upper respiratory tract infection/influenza, respiratory tract infection, arthralgia/myalgia, dysgeusia, headache, dyspepsia, decreased appetite, constipation, stomatitis, dyspnea, and thrombocytopenia.

The recommended olaparib dose is 300 mg taken orally twice daily with or without food.