In September 2021, the FDA granted accelerated approval to mobocertinib (Exkivity; Takeda Pharmaceutical Company Limited) for the treatment of adults with locally advanced or metastatic non–small cell lung cancer (NSCLC)
with EGFR exon 20 insertion mutations who have disease progression on or
after platinum-based chemotherapy. However, continued approval for this indication of the drug may be contingent on verification and description of clinical benefit in confirmatory trials.1
Lung cancer is the second most common cancer in both men and women.2 The American Cancer Society estimates that 236,740 new cases of lung cancer will be diagnosed in the United States in 2022; NSCLC is the most common form, accounting for approximately 84% of all lung cancers.2 Further, patients with NSCLC with EGFR exon 20 insertion mutations account for approximately 1% to 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 that was also approved by the FDA.3
The FDA approval of this indication of mobocertinib was based on results from an international, nonrandomized, open-label, multicohort clinical trial (NCT02716116).1,4 The trial included 114 patients with NSCLC with EGFR exon 20 insertion mutations who had previously received platinum-based chemotherapy.
During the trial, the patients were treated at a 160-mg dose of mobocertinib.3 Efficacy measures for the trial were overall response rate (ORR) and duration of response (DOR); the ORR during the trial was 28%, and the median DOR was 17.5 months.3,4
Based on the trial results, the FDA granted the application priority review, breakthrough therapy designation, and orphan drug designation.1
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, who have disease progression 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
Depending on the severity of the following clinically significant adverse effects (AEs), providers may withhold, dose reduce, or permanently discontinue mobocertinib3,4:
- Heart rate–corrected QT (QTc) interval prolongation, including torsade de pointes, can be fatal.
- Pneumonitis can also be fatal.
- Cardiac toxicity, including decreased ejection fraction, cardiomyopathy, and congestive heart failure, can be fatal.
- Severe diarrhea, which can lead to dehydration or electrolyte imbalance, with or without renal impairment
Common AEs of mobocertinib that are generally less serious include diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain.4
Certain medications are known to affect mobocertinib’s efficacy and safety. For this reason, patients should avoid concomitant use of mobocertinib when taking the following medications4:
- Strong or moderate cytochrome P450 (CYP) 3A inhibitors—These medications increase mobocertinib plasma concentrations, which can raise the risk of adverse reactions. 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, reducing the efficacy of mobocertinib’s antitumor activity.
Patient Counseling Information
Pharmacists should be sure to counsel patients taking mobocertinib on the following points3,4:
- Since mobocertinib can cause QTc interval prolongation and torsade de pointes, before taking the drug, patients should 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 should report the occurrence of symptoms including dizziness, light-headedness, and syncope, which may be indicative of significant QTc prolongation. Mobocertinib labeling has a boxed warning for this condition.
- The drug can cause severe lung problems that 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 that can be fatal. Providers must monitor cardiac function before initiating and during therapy with mobocertinib. Patients must contact their providers immediately if they experience signs or symptoms of heart failure, such as palpitations, shortness of breath, chest pain, and syncope.
- The agent can cause severe diarrhea, which should be treated promptly. When diarrhea occurs, patients must immediately call their providers, 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 nonhormonal contraception during treatment with mobocertinib and for 1 month after the last dose. Additionally, mobocertinib may render hormonal contraceptives ineffective. Men with female partners of reproductive potential must also use effective contraception during treatment with mobocertinib and for 1 week after the last dose.
- Women must not breastfeed during treatment with mobocertinib and for 1 week after the last dose because it is currently unknown whether the drug can be passed through breast milk and what its effect may be on breastfed children.
- Patients who miss a dose of mobocertinib by more than 6 hours or experience vomiting occurs should skip the dose or not take an additional dose and then take the next dose as prescribed the following day.
- Patients taking mobocertinib must avoid grapefruit or grapefruit juice, which may increase the amount of mobocertinib in the blood.
- Mobocertinib may impair fertility in men and women of reproductive potential, which is something patients should be aware of when taking the drug.
Yvonne Riley-Poku, PharmD, is a registered pharmacist based in Connecticut.
- FDA grants accelerated approval to mobocertinib for metastatic non-small cell lung cancer with EGFR exon 20 insertion mutations. FDA. Updated 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
- Key statistics for lung cancer. American Cancer Society. Updated January 12, 2022. Accessed January 14, 2022. https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html
- 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. News release. 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 USA Inc; 2021. Accessed October 26, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215310s000lbl.pdf