- 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.
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 61% of patients with ovarian cancer treated with ELAHERE. Nine percent (9%) of patients experienced Grade 3 ocular adverse reactions, including visual impairment, keratopathy/keratitis (corneal disorders), dry eye, photophobia, and eye pain; and one patient (0.2%) experienced Grade 4 keratopathy. The most common (≥5%) ocular adverse reactions were visual impairment (49%), keratopathy (36%), dry eye (26%), cataract (15%), photophobia (13%), and eye pain (12%).
The median time to onset for first ocular adverse reaction was 1.2 months (range: 0.03 to 12.9). Of the patients who experienced ocular events, 49% had complete resolution and 39% 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 0.6% 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.
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 0.8% with Grade 3 events, and 1 patient (0.2%) with a Grade 4 event. One patient (0.2%) died due to respiratory failure in the setting of pneumonitis and lung metastases.
Monitor patients for pulmonary signs and symptoms of pneumonitis. Infectious, neoplastic, and other causes for 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.
PN occurred in 36% of patients with ovarian cancer treated with ELAHERE across clinical trials; 2% of patients experienced Grade 3 PN. PN adverse reactions included peripheral neuropathy (19%), peripheral sensory neuropathy (9%), paraesthesia (6%), neurotoxicity (3%), hypoaesthesia (2%), peripheral motor neuropathy (1%), neuralgia (0.4%), polyneuropathy (0.2%) and oral hypoesthesia (0.2%).
Monitor patients for signs and symptoms of neuropathy. For patients experiencing new or worsening PN, withhold dosage, dose reduce, or permanently discontinue ELAHERE based on the severity of PN.
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.
Serious adverse reactions occurred in 31% of patients. The most common (≥2%) serious adverse reactions were intestinal obstruction (8%), ascites (4%), infection (3%), and pleural effusion (3%). Fatal adverse reactions occurred in 2% of patients, including small intestinal obstruction (1%) and pneumonitis (1%).
Permanent discontinuation of ELAHERE due to adverse reactions occurred in 11% of patients. The most common (≥2%) adverse reactions leading to permanent discontinuation were intestinal obstruction (2%) and thrombocytopenia (2%). One patient (0.9%) permanently discontinued ELAHERE due to visual impairment (unilateral decrease to BCVA ≤20/200 that resolved to baseline after discontinuation).
Dosage delays of ELAHERE due to an adverse reaction occurred in 39% of patients. Adverse reactions which required dosage delays in ≥3% of patients included visual impairment (15%), keratopathy (11%), neutropenia (6%), dry eye (5%), cataracts (3%) and increased gamma-glutamyltransferase (3%).
Dose reductions of ELAHERE due to an adverse reaction occurred in 20% of patients. Adverse reactions which required dose reductions in ≥3% of patients included visual impairment (9%) and keratopathy (7%).
The most common (≥20%) adverse reactions, including laboratory abnormalities, were vision impairment, fatigue, increased aspartate aminotransferase, nausea, increased alanine aminotransferase, keratopathy, abdominal pain, decreased lymphocytes, peripheral neuropathy, diarrhea, decreased albumin, constipation, increased alkaline phosphatase, dry eye, decreased magnesium, decreased leukocytes, decreased neutrophils, and decreased hemoglobin.
DM4 is a CYP3A4 substrate. Concomitant use of ELAHERE with strong CYP3A4 inhibitors may increase unconjugated DM4 exposure, which may increase the risk of ELAHERE adverse reactions. Closely monitor patients for adverse reactions with ELAHERE when used concomitantly with strong CYP3A4 inhibitors.
Advise women not to breastfeed during treatment with ELAHERE and for at least 1 month after the last dose.
Safety and effectiveness of ELAHERE have not been established in pediatric patients.
Avoid use of ELAHERE in patients with moderate or severe hepatic impairment (total bilirubin >1.5 ULN).
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.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Please see full Prescribing Information including BOXED WARNING.