Bayer Announces Results of Sub-group Analysis for Vitrakvi® (larotrectinib) in Patients with NTRK Gene Fusion-Positive Metastatic Non-small Cell Lung Cancer (NSCLC)
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WHIPPANY, N.J., April 11, 2019 /PRNewswire/ -- Bayer today presented subgroup analysis data of patients with non-small cell lung cancer with neurotrophic receptor tyrosine kinase (NTRK) gene fusion treated with Vitrakvi® (larotrectinib).1 Vitrakvi is the only TRK inhibitor exclusively designed for the treatment of adult and pediatric patients with solid tumors that have an NTRK gene fusion without a known acquired resistance mutation that are either metastatic or where surgical resection will likely result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment.2 In the U.S., Vitrakvi was approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
The analysis assessed 11 advanced metastatic NSCLC patients from two clinical studies, of which seven were evaluable for response. This sub-set showed an overall response rate (ORR) of 71 percent, including one complete response (CR) and four partial responses (PR), based on investigator assessment using RECIST version 1.1. These data include Vitrakvi patients with and without brain metastasis, with a median time to response of 1.8 months. Median duration of response (DOR) was not reached at the time of the analysis (DOR ranged from 7.4 to 17.6 months, with responses ongoing). Adverse events (AEs) were generally consistent with previously reported safety profile of Vitrakvi.1 Treatment emergent AEs (>20%) across all grades include fatigue, dizziness, nausea, constipation, anemia, AST/ALT increase, cough, diarrhea, and vomiting.1 These data were presented at the European Lung Cancer Congress (ELCC) 2019, taking place in Geneva, Switzerland, from April 10-13, 2019. "The efficacy and safety of larotrectinib in patients with NSCLC reinforce the importance of identifying genomic alterations early," said Alexander Drilon, M.D., clinical director of Early Drug Development Service at Memorial Sloan Kettering Cancer Center. "Lung cancer is the leading cause of cancer deaths in the United States and these data are important to progressing the treatment options available for these patients in order to provide appropriate care." "As researchers learn more about tumor genomics, new medicines that directly address the genomic abnormalities driving tumor growth become increasingly relevant for patients," said Scott Fields, MD, Senior Vice President and Head of Oncology Development at Bayer's Pharmaceutical Division. "These latest Vitrakvi data in NSCLC underscore the importance of genomic cancer testing in all NSCLC patients." Vitrakvi was approved in the U.S. in November 2018. Bayer has submitted a Marketing Authorization Application (MAA) in the European Union and additional filings in other regions are underway. Under a change-in-control clause in the collaboration agreement with Loxo Oncology, Bayer exercised its option to obtain the exclusive licensing rights for the global development and commercialization, including the U.S., for larotrectinib (Vitrakvi®) as well as BAY 2731954 (formerly LOXO-195). About Vitrakvi® (larotrectinib) This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Research suggests that the NTRK genes can become abnormally fused to other genes, producing a TRK fusion protein that can act as an oncogenic driver, leading to cancer cell growth and survival.2 Important Safety Information Neurotoxicity: Among the 176 patients who received VITRAKVI, neurologic adverse reactions of any grade occurred in 53% of patients, including Grade 3 and Grade 4 neurologic adverse reactions in 6% and 0.6% of patients, respectively. The majority (65%) of neurological adverse reactions occurred within the first three months of treatment (range 1 day to 2.2 years). Grade 3 neurologic adverse reactions included delirium (2%), dysarthria (1%), dizziness (1%), gait disturbance (1%), and paresthesia (1%). Grade 4 encephalopathy (0.6%) occurred in a single patient. Neurologic adverse reactions leading to dose modification included dizziness (3%), gait disturbance (1%), delirium (1%), memory impairment (1%), and tremor (1%).2 Advise patients and caretakers of these risks with VITRAKVI. Advise patients not to drive or operate hazardous machinery if they are experiencing neurologic adverse reactions. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dose when resumed.2 Hepatotoxicity: Among the 176 patients who received VITRAKVI, increased transaminases of any grade occurred in 45%, including Grade 3 increased AST or ALT in 6% of patients. One patient (0.6%) experienced Grade 4 increased ALT. The median time to onset of increased AST was 2 months (range: 1 month to 2.6 years). The median time to onset of increased ALT was 2 months (range: 1 month to 1.1 years). Increased AST and ALT leading to dose modifications occurred in 4% and 6% of patients, respectively. Increased AST or ALT led to permanent discontinuation in 2% of patients.2 Monitor liver tests, including ALT and AST, every 2 weeks during the first month of treatment, then monthly thereafter, and as clinically indicated. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dosage when resumed.2 Embryo-Fetal Toxicity: VITRAKVI can cause fetal harm when administered to a pregnant woman. Larotrectinib resulted in malformations in rats and rabbits at maternal exposures that were approximately 11- and 0.7-times, respectively, those observed at the clinical dose of 100 mg twice daily.2 Advise women of the potential risk to a fetus. Advise females of reproductive potential to use an effective method of contraception during treatment and for 1 week after the final dose of VITRAKVI.2 Most Common Adverse Reactions (≥20%): The most common adverse reactions (≥20%) were: increased ALT (45%), increased AST (45%), anemia (42%), fatigue (37%), nausea (29%), dizziness (28%), cough (26%), vomiting (26%), constipation (23%), and diarrhea (22%).2 Drug Interactions: Avoid coadministration of VITRAKVI with strong CYP3A4 inhibitors (including grapefruit or grapefruit juice), strong CYP3A4 inducers (including St. John's wort), or sensitive CYP3A4 substrates. If coadministration of strong CYP3A4 inhibitors or inducers cannot be avoided, modify the VITRAKVI dose as recommended. If coadministration of sensitive CYP3A4 substrates cannot be avoided, monitor patients for increased adverse reactions of these drugs.2 Lactation: Advise women not to breastfeed during treatment with VITRAKVI and for 1 week after the final dose.2 Please see the full Prescribing Information. About TRK Fusion Cancer About Oncology at Bayer About Bayer © 2019 Bayer Media Contact: Forward-Looking Statements References PP-LAR-US-0814-1 Intended for U.S. Media Only
SOURCE Bayer |
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