In September 2021, the FDA granted accelerated approval to mobocertinib (Exkivity; Takeda Pharmaceuticals) for adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations. Eligible patients should have disease progression while on or after platinum-based chemotherapy. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.1
Lung cancer is the second most common form of the disease in both men and women.2 The American Cancer Society estimates that physicians will diagnose 235,760 cases of lung cancer in the United States in 2021. NSCLC is the most common form of lung cancer, accounting for approximately 80%-85% of all cases.2
Patients with EGFR exon 20 insertion mutation NSCLC account for approximately 1%-2% of NSCLC cases.3 Oncologists select patients for treatment with mobocertinib based on the presence of EGFR exon 20 insertion mutations detected using Oncomine Dx Target Test (Thermo Fisher Scientific), a companion diagnostic device also approved by the FDA.3
The FDA approval for this indication was based on results from an international, non-randomized, open label, multicohort clinical trial (NCT02716116).1,4 The trial included 114 patients with EGFR exon 20 insertion mutation NSCLC who had previously received platinum-based chemotherapy.
The patients were treated at the 160 mg dose.3 The FDA granted the application priority review, breakthrough therapy designation, and orphan drug designation.1
Efficacy measures for the trial were overall response rate (ORR) and duration of response (DoR). The ORR was 28% and a median DoR at 17.5 months.3,4
Indications for Use
Mobocertinib is indicated for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.4
Mechanism of Action
Mobocertinib is a tyrosine kinase inhibitor that selectively targets and inhibits EGFR exon 20 insertion mutations.3,4
Dosage and Administration
The recommended mobocertinib dose is 160 mg orally once daily until disease progression or unacceptable toxicity. Patients may take mobocertinib with or without food at the same time each day.4
Adverse Events (AEs)
Depending on the severity of the following clinically significant AEs, providers may withhold, reduce the dose, or permanently discontinue mobocertinib:3,4
- QTc prolongation and torsades de pointes—mobocertinib can cause life threatening heart rate corrected QTc prolongation including torsades de pointes, which can be fatal.
- Interstitial lung disease (ILD)/pneumonitis—mobocertinib can cause ILD/pneumonitis, which can be fatal.
- Cardiac toxicity—mobocertinib can cause cardiac toxicity including decreased ejection fraction, cardiomyopathy, and congestive heart failure, which can be fatal.
- Diarrhea—mobocertinib can cause severe diarrhea which can lead to dehydration or electrolyte imbalance, with or without renal impairment.
Common AEs include diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain.4
Certain medications have effects on mobocertinib. Patients must avoid concomitant use of mobocertinib with these medications:4
- Strong or moderate CYP3A inhibitors—these medications increase mobocertinib plasma concentrations, thus increasing the risk of AEs. If concomitant use of moderate CYP3A inhibitors cannot be avoided, providers must reduce the mobocertinib dose and frequently monitor the QTc interval.
- Strong or moderate CYP3A inducers—these medications decrease mobocertinib plasma concentrations thus reducing mobocertinib anti-tumor activity.
Patient Counseling Information
Pharmacists need to counsel patients on several points:3,4
- Mobocertinib can cause QTc interval prolongation and torsades de pointes. Before taking mobocertinib, patients must inform their health care provider of all medical conditions, including cardiac problems and long QTc syndrome. Patients must avoid use of concomitant drugs that are known to prolong the QTc interval, and also report symptoms including dizziness, lightheadedness, and syncope, which may be indicative of significant QTC prolongation. Mobocertinib labeling has a boxed warning for this condition.
- Mobocertinib can cause severe lung problems, which can be fatal. Patients must contact their providers right away to report new or worsening respiratory symptoms, such as cough, shortness of breath, or chest pain.
- Mobocertinib can cause heart problems, which can be fatal. Providers must monitor cardiac function before initiating and during therapy with mobocertinib. Patients must contact their providers immediately if they experience any signs or symptoms of heart failure, such as palpitations, shortness of breath, chest pain, and syncope.
- Mobocertinib can cause severe diarrhea and should be treated promptly. When diarrhea occurs, patients must call their providers right away, who may advise them to take antidiarrheal medicine and increase oral fluids and electrolyte intake.
- Mobocertinib can cause fetal harm. Female patients of reproductive potential must use effective non-hormonal contraception during treatment with mobocertinib, and for 1 month after the last dose. Mobocertinib may render hormonal contraceptives ineffective. Males with female partners of reproductive potential must also use effective contraception during treatment with mobocertinib, and for 1 week after the last dose.
- It is not known if mobocertinib passes into breastmilk and its effect on breastfed children. Women must not breastfeed during treatment with mobocertinib and for 1 week after the last dose.
- When patients miss a dose of mobocertinib by more than 6 hours or when vomiting occurs, they must skip the dose or not take an additional dose, and take the next dose as prescribed the following day.
- Patients must avoid grapefruit or grapefruit juice while taking mobocertinib. Grapefruit may increase the amount of mobocertinib in the blood.
- Mobocertinib may impair fertility in males and females of reproductive potential.
- U.S Food and Drug Administration. FDA grants accelerated approval to mobocertinib for metastatic non-small cell lung cancer with EGFR exon 20 insertion mutations. September 16, 2021. Accessed October 26, 2021. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-mobocertinib-metastatic-non-small-cell-lung-cancer-egfr-exon-20
- American Cancer Society. What is lung cancer? Accessed October 26, 2021. https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html
- Takeda News Releases. Takeda’s Exkivity (mobocertinib) approved by the U.S. FDA as the first oral therapy specifically designed for patients with EGFR Exon 20 insertion+ NSCLC. September 15, 2021. Accessed October 26, 2021. https://www.takeda.com/newsroom/newsreleases/2021/takeda-exkivity-mobocertinib-approved-by-us-fda/
- Exkivity Prescribing Information. Takeda Pharmaceuticals U.S.A., Inc.; 2021. Accessed October 26, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215310s000lbl.pdf