INDICATION
ELAHERE is indicated for the treatment of adult patients with folate receptor-alpha (FRα) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. Select patients for therapy based on an FDA-approved test.
Please see Full Prescribing Information, including BOXED WARNING.
IMPORTANT SAFETY INFORMATION
Please see additional Important Safety Information, including BOXED WARNING, below.
Epithelial Ovarian Cancer: An Overview
Epithelial ovarian cancer accounts for 4% of deaths among female cancer patients, ranking as the sixth most common cause of cancer-related mortality in women.1 Risk factors for developing epithelial ovarian cancer include having a family history of breast or ovarian cancer, a personal history of breast cancer, endometriosis, pelvic inflammatory disease, and being tall in adulthood.1
Approximately 90% of patients with ovarian cancer express folate receptor alpha (FRα) in their cancer cells.2-4 An FRα-positive patient is defined as having more than 75% of viable tumor cells staining with ≥2+ intensity.5 Patients are treated with platinum-based chemotherapy6 and are classified as platinum-resistant when the platinum-free intervals (PFI) are less than 6 months.7
ADCs for Platinum-Resistant Ovarian, Fallopian Tube, or Peritoneal Cancer
Mirvetuximab soravtansine-gynx (ELAHERE®) is an antibody-drug conjugate (ADC) indicated for the treatment of adult patients with folate receptor-alpha (FRα) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received one to three prior systemic treatment regimens.6
The antibody is a chimeric IgG1 that targets the folate receptor alpha (FRα). It is linked to a small molecule, DM4, which is a microtubule inhibitor connected to the antibody through a cleavable linker.6 When the antibody binds to FRα, it is internalized by the cell, leading to the release of DM4 through proteolytic cleavage.6 DM4 then disrupts the microtubule network within the cell, causing cell cycle arrest and ultimately resulting in apoptotic cell death.6
ELAHERE® is associated with potential adverse events, including ocular adverse events (OAEs) such as visual impairment, keratopathy, dry eye, eye pain, photophobia, and uveitis.6 The underlying mechanisms of ocular toxicities have not been fully elucidated.8
With this treatment, ECPs must be aware of the specific boxed warning concerning possible OAEs. These OAEs may result in the permanent discontinuation of ELAHERE®6, making it essential to manage these patients effectively to minimize the risk of discontinuation.
Prevalence of Ocular Adverse Events
Approximately 59% of patients experienced OAEs in clinical trials; 11% had grade 3 OAEs, and 0.3% (two patients) had grade 4 OAEs (one with keratopathy and another with cataract).6 With ELAHERE® treatment, the most common OAEs are blurred vision and keratopathy. Table 1 has the most common OAEs associated with ELAHERE® therapy.6
Table 1: Most Common OAEs In Patients Treated With ELAHERE®6
Keratopathy encompasses various corneal disorders, including corneal epithelial microcysts, keratitis, corneal deposits, punctate keratitis, and corneal opacity (Figures 1-3).6
Figure 1
Figure 2
Figure 3
Figures 1-3: Epithelial Microcysts And Keratopathy Resulting In Corneal Haze And Decreased Vision. Photos Provided Courtesy Of Jarrod Needle And Randy King.
Importantly, for patients and doctors, there are strategies to proactively manage OAEs, including dose modification, ophthalmic examinations, and prescribing topical steroids and lubricating eye drops.6 Over 50% of patients had their OAEs resolved without requiring dose modification.6
Identifying and Diagnosing Ocular Side Effects of ELAHERE®
Familiarity with the most common OAEs associated with ELAHERE® treatment can help ECPs better care for patients on the medication and more confidently collaborate with the patient’s oncology team to modify treatment and, if necessary, to manage symptoms.6 ECPs are well-equipped to manage the most common OAEs associated with ELAHERE® treatment, including visual impairment, keratopathy, dry eye, and photophobia.6
Onset of Ocular Adverse Events in Patients Treated with ELAHERE®
A thorough ocular evaluation of patients undergoing ELAHERE® therapy is important to obtain before initiating treatment, as it serves as a helpful baseline upon which ECPs can better track and document change throughout the treatment cycle.6 A cycle on ELAHERE® is 3 weeks long, and patients are examined every other cycle for the first 8 cycles.6
While OAEs are common with ELAHERE® treatment, 1% of patients in clinical trials had to discontinue ELAHERE® treatment secondary to OAEs.6 The median duration of treatment was 4.4 months in clinical trials, and the median onset time of OAEs occurred during the second cycle of treatment at 5.1 weeks.6 These OAEs were mostly grade 1 and 2, which can be managed with dose modification and treatment.6
In our opinion, these OAEs emphasize the role of the ECP within the patient's multidisciplinary care team in helping alleviate ocular symptoms and systemic treatment management.
Management Strategies and Best Practices for ECPs
Before the initiation of ELAHERE® therapy, an ocular assessment is needed.6 At each office visit, assess visual acuity and perform a slit lamp examination.6 After the initial pretreatment ocular evaluation, patients need to be assessed every other treatment cycle (each cycle lasts 3 weeks, so every 6 weeks) for the first 8 cycles (6 months) of treatment.6
Since patients may develop OAEs such as photophobia and dry eye, they should be educated on proper eye health management.6 This includes wearing sunglasses during the day and avoiding wearing contact lenses, unless medically necessary.6
AbbVie has an
Ocular Assessment Form to help facilitate collaborative care between ECPs and oncologists. This useful assessment form can be used in the initial examination of these patients and for ongoing monitoring.
The oncology team will refer patients to an ECP for any new or worsening ocular signs and symptoms and will inform them to contact their ECP immediately about any changes in symptoms (e.g., blurred vision).6 See Table 2 for eye care guidelines during treatment with ELAHERE®.6
Table 2: Eye Care Guidelines During Therapy With ELAHERE®6
Clinical trials of ELAHERE® recommend regular ophthalmic examinations, premedication with topical steroids and lubricating eye drops, and appropriate dose modifications.6 Table 3 outlines the recommended ELAHERE® dose modification based on the patient’s OAEs.6
Table 3: Dose Modifications For OAEs6
It has been hypothesized that ophthalmic topical steroids can slow the proliferation of limbal stem cells, potentially leading to reduced sensitivity to the damaging effects of chemotherapeutics.8 Ophthalmic topical steroids may also contribute to the thinning of the corneal epithelium, thereby facilitating the shedding of corneal microcysts induced by exposure to an ADC.8
The prophylactic use of ophthalmic topical steroids is recommended with ELAHERE® and should only be prescribed after an initial ophthalmic examination and subsequent exams.6
Patients should use preservative-free lubricating artificial tears and topical steroid eye drops starting the day before their first dose and continuing through day 8 of each cycle (Figure 4).6 The schedule for ophthalmic topical steroids is six times daily on the day before infusion and on days 1 to 4, and four times daily on days 5 to 8 of each cycle. Additionally, patients are advised to use preservative-free, lubricating eye drops four times daily and as needed.6
Figure 4. Ophthalmic Topical Steroid and Lubricating Eye Drop Schedule6
The ultimate goal is to enable prompt intervention with dosage modification to limit unnecessary discontinuations in treatment. Careful examination and documentation of any changes in visual acuity or ocular toxicity observed on slit lamp findings are crucial for managing these OAEs and guiding the oncologist on potentially altering the ELAHERE® dosage (to delay, reduce, or permanently discontinue treatment based on severity and persistence of symptoms).6
Note: Download the ELAHERE® OCULAR BILLING AND CODING GUIDE to leverage as a reference for examples of billing and coding information that may be appropriate to facilitate eye exams for these patients. IMPORTANT SAFETY INFORMATION
WARNING: OCULAR TOXICITY
- ELAHERE can cause severe ocular toxicities, including visual impairment, keratopathy, dry eye, photophobia, eye pain, and uveitis.
- Conduct an ophthalmic exam including visual acuity and slit lamp exam prior to initiation of ELAHERE, every other cycle for the first 8 cycles, and as clinically indicated.
- Administer prophylactic artificial tears and ophthalmic topical steroids.
- Withhold ELAHERE for ocular toxicities until improvement and resume at the same or reduced dose.
- Discontinue ELAHERE for Grade 4 ocular toxicities.
WARNINGS and PRECAUTIONS
Ocular Disorders
ELAHERE can cause severe ocular adverse reactions, including visual impairment, keratopathy (corneal disorders), dry eye, photophobia, eye pain, and uveitis.
Ocular adverse reactions occurred in 59% of patients with ovarian cancer treated with ELAHERE. Eleven percent (11%) of patients experienced Grade 3 ocular adverse reactions, including blurred vision, keratopathy (corneal disorders), dry eye, cataract, photophobia, and eye pain; two patients (0.3%) experienced Grade 4 events (keratopathy and cataract). The most common (≥5%) ocular adverse reactions were blurred vision (48%), keratopathy (36%), dry eye (27%), cataract (16%), photophobia (14%), and eye pain (10%).
Please see additional Important Safety Information, including BOXED WARNING, at the end of the article
Case Studies
Case Study 1 - Steroid Responder
Case Study 2 - Reduced Visual Acuity
Despite these two case encounters, it is important to note that we have had patients on ELAHERE® who present with keratopathy without a steroid response or cataract, creating a less complicated case. In our practice, we generally approach these cases by increasing topical steroids (with close monitoring) as we find it can make a positive difference as far as keratopathy goes for many of these patients. We also consider adding cyclosporine or other topical anti-inflammatory-based dry eye drops to their treatment schedule, which we have found beneficial.
ECPs Play a Critical Role In the Patient Journey
Patients with platinum-resistant ovarian cancer have a poor prognosis; therefore, vision impairment and blurred vision can affect their quality of life. The goal of closer monitoring and preventative treatment is to maximize adherence to cancer treatment. Since ocular side effects can occur with therapy, it is important to maintain communication with the patient’s oncologist. ELAHERE® prescriber information outlines suggested dose reduction based on certain ocular findings. Because the mechanism of toxicity to the cornea of these medications is unclear, difficult management situations and dilemmas may arise.
That begs the question as to when ECPs should consider referring. Based on available information, general eye care professionals who are familiar with ELAHERE® and knowledgeable about its possible ocular side effects should be able to manage and treat most ocular side effects of ELAHERE®. Patients with co-existing or comorbid corneal disease or who develop severe keratopathy may benefit from an evaluation by a corneal specialist. Patients with secondary glaucoma due to steroid response not responsive to medical management may require referral to a glaucoma specialist.
Regardless, collaborative care is critical to optimizing the patient experience and journey. OAEs are a common finding with ELAHERE® therapy. ECPs possess the knowledge to diagnose and manage any corneal or refractive changes and report these to the managing oncologist for potential ELAHERE® dose modification.
It is important for ECPs to report any OAEs to the treating oncologist so they can determine if modifications of ELAHERE® are necessary. In the clinical trial, 1% of patients discontinued therapy with ELAHERE® due to an OAE.
Recognizing the vital role that ECPs play in the treatment journeys of these patients is crucial; they can significantly assist in helping patients adhere to their treatment plans.
IMPORTANT SAFETY INFORMATION AND INDICATION
WARNING: OCULAR TOXICITY
- ELAHERE can cause severe ocular toxicities, including visual impairment, keratopathy, dry eye, photophobia, eye pain, and uveitis.
- Conduct an ophthalmic exam including visual acuity and slit lamp exam prior to initiation of ELAHERE, every other cycle for the first 8 cycles, and as clinically indicated.
- Administer prophylactic artificial tears and ophthalmic topical steroids.
- Withhold ELAHERE for ocular toxicities until improvement and resume at the same or reduced dose.
- Discontinue ELAHERE for Grade 4 ocular toxicities.
WARNINGS and PRECAUTIONS
Ocular Disorders
ELAHERE can cause severe ocular adverse reactions, including visual impairment, keratopathy (corneal disorders), dry eye, photophobia, eye pain, and uveitis.
Ocular adverse reactions occurred in 59% of patients with ovarian cancer treated with ELAHERE. Eleven percent (11%) of patients experienced Grade 3 ocular adverse reactions, including blurred vision, keratopathy (corneal disorders), dry eye, cataract, photophobia, and eye pain; two patients (0.3%) experienced Grade 4 events (keratopathy and cataract). The most common (≥5%) ocular adverse reactions were blurred vision (48%), keratopathy (36%), dry eye (27%), cataract (16%), photophobia (14%), and eye pain (10%).
The median time to onset for first ocular adverse reaction was 5.1 weeks (range: 0.1 to 68.6). Of the patients who experienced ocular events, 53% had complete resolution; 38% had partial improvement (defined as a decrease in severity by one or more grades from the worst grade at last follow up). Ocular adverse reactions led to permanent discontinuation of ELAHERE in 1% of patients.
Premedication and use of lubricating and ophthalmic topical steroid eye drops during treatment with ELAHERE are recommended. Advise patients to avoid use of contact lenses during treatment with ELAHERE unless directed by a healthcare provider.
Refer patients to an eye care professional for an ophthalmic exam including visual acuity and slit lamp exam prior to treatment initiation, every other cycle for the first 8 cycles, and as clinically indicated. Promptly refer patients to an eye care professional for any new or worsening ocular signs and symptoms.
Monitor for ocular toxicity and withhold, reduce, or permanently discontinue ELAHERE based on severity and persistence of ocular adverse reactions.
Pneumonitis
Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ELAHERE.
Pneumonitis occurred in 10% of patients treated with ELAHERE, including 1% with Grade 3 events and 1 patient (0.1%) with a Grade 4 event. One patient (0.1%) died due to respiratory failure in the setting of pneumonitis and lung metastases. One patient (0.1%) died due to respiratory failure of unknown etiology. Pneumonitis led to permanent discontinuation of ELAHERE in 3% of patients.
Monitor patients for pulmonary signs and symptoms of pneumonitis, which may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams. Infectious, neoplastic, and other causes for such symptoms should be excluded through appropriate investigations. Withhold ELAHERE for patients who develop persistent or recurrent Grade 2 pneumonitis until symptoms resolve to ≤ Grade 1 and consider dose reduction. Permanently discontinue ELAHERE in all patients with Grade 3 or 4 pneumonitis. Patients who are asymptomatic may continue dosing of ELAHERE with close monitoring.
Peripheral Neuropathy (PN)
Peripheral neuropathy occurred in 36% of patients with ovarian cancer treated with ELAHERE across clinical trials; 3% of patients experienced Grade 3 peripheral neuropathy. Peripheral neuropathy adverse reactions included peripheral neuropathy (20%), peripheral sensory neuropathy (9%), paraesthesia (6%), neurotoxicity (3%), hypoaesthesia (1%), peripheral motor neuropathy (0.9%), polyneuropathy (0.3%), and peripheral sensorimotor neuropathy (0.1%). Monitor patients for signs and symptoms of neuropathy, such as paresthesia, tingling or a burning sensation, neuropathic pain, muscle weakness, or dysesthesia. For patients experiencing new or worsening PN, withhold dosage, dose reduce, or permanently discontinue ELAHERE based on the severity of PN.
Embryo-Fetal Toxicity
Based on its mechanism of action, ELAHERE can cause embryo-fetal harm when administered to a pregnant woman because it contains a genotoxic compound (DM4) and affects actively dividing cells.
Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ELAHERE and for 7 months after the last dose.
ADVERSE REACTIONS
The most common (≥20%) adverse reactions, including lab abnormalities, were increased aspartate aminotransferase, fatigue, increased alanine aminotransferase, blurred vision, nausea, increased alkaline phosphatase, diarrhea, abdominal pain, keratopathy, peripheral neuropathy, musculoskeletal pain, decreased lymphocytes, decreased platelets, decreased magnesium, decreased hemoglobin, dry eye, constipation, decreased leukocytes, vomiting, decreased albumin, decreased appetite, and decreased neutrophils.
DRUG INTERACTIONS
DM4 is a CYP3A4 substrate. Closely monitor patients for adverse reactions with ELAHERE when used concomitantly with strong CYP3A4 inhibitors.
USE IN SPECIAL POPULATIONS
Lactation
Advise women not to breastfeed during treatment with ELAHERE and for 1 month after the last dose.
Hepatic Impairment
Avoid use of ELAHERE in patients with moderate or severe hepatic impairment (total bilirubin >1.5 ULN).
INDICATION
ELAHERE is indicated for the treatment of adult patients with folate receptor-alpha (FRα) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. Select patients for therapy based on an FDA-approved test.
Please see Full Prescribing Information, including BOXED WARNING.
