IMPORTANT SAFETY INFORMATION
Hepatotoxicity
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LUMAKRAS® can cause hepatotoxicity and increased ALT or AST
which may lead to drug-induced liver injury and hepatitis.
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In the pooled safety population of NSCLC patients who received single
agent LUMAKRAS® 960 mg hepatotoxicity occurred in 27% of
patients, of which 16% were Grade ≥ 3. Among patients with hepatotoxicity
who required dosage modifications, 64% required treatment with
corticosteroids.
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In this pooled safety population of NSCLC patients who received single
agent LUMAKRAS® 960 mg, 17% of patients who received
LUMAKRAS® had increased alanine aminotransferase
(ALT)/increased aspartate aminotransferase (AST); of which 9% were Grade ≥
3. The median time to first onset of increased ALT/AST was 6.3 weeks
(range: 0.4 to 42). Increased ALT/AST leading to dose interruption or
reduction occurred in 9% of patients treated with LUMAKRAS®.
LUMAKRAS® was permanently discontinued due to increased ALT/AST
in 2.7% of patients. Drug-induced liver injury occurred in 1.6% (all
grades) including 1.3% (Grade ≥ 3).
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In this pooled safety population of NSCLC patients who received single
agent LUMAKRAS® 960 mg, a total of 40% patients with recent (≤
3 months) immunotherapy prior to starting LUMAKRAS® had an
event of hepatotoxicity. An event of hepatotoxicity was observed in 18% of
patients who started LUMAKRAS® more than 3 months after last
dose of immunotherapy and in 17% of those who never received
immunotherapy. Regardless of time from prior immunotherapy, 94% of
hepatotoxicity events improved or resolved with dosage modification of
LUMAKRAS®, with or without corticosteroid treatment.
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Monitor liver function tests (ALT, AST, alkaline phosphatase, and total
bilirubin) prior to the start of LUMAKRAS®, every 3 weeks for
the first 3 months of treatment, then once a month or as clinically
indicated, with more frequent testing in patients who develop transaminase
and/or bilirubin elevations. Withhold, reduce the dose or permanently
discontinue LUMAKRAS® based on severity of the adverse
reaction. Consider administering systemic corticosteroids for the
management of hepatotoxicity.
Interstitial Lung Disease (ILD)/Pneumonitis
- LUMAKRAS® can cause ILD/pneumonitis that can be fatal.
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In the pooled safety population of NSCLC patients who received single
agent LUMAKRAS® 960 mg ILD/pneumonitis occurred in 2.2% of
patients, of which 1.1% were Grade ≥ 3, and 1 case was fatal. The median
time to first onset for ILD/pneumonitis was 8.6 weeks (range: 2.1 to 36.7
weeks). LUMAKRAS® was permanently discontinued due to
ILD/pneumonitis in 1.3% of LUMAKRAS®-treated patients. Monitor
patients for new or worsening pulmonary symptoms indicative of
ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold
LUMAKRAS® in patients with suspected ILD/pneumonitis and
permanently discontinue LUMAKRAS® if no other potential causes
of ILD/pneumonitis are identified.
Most Common Adverse Reactions
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The most common adverse reactions ≥ 20% were diarrhea, musculoskeletal
pain, nausea, fatigue, hepatotoxicity, and cough.
Drug Interactions
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Advise patients to inform their healthcare provider of all concomitant
medications, including prescription medicines, over‑the‑counter drugs,
vitamins, dietary and herbal products.
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Inform patients to avoid proton pump inhibitors and H2 receptor
antagonists while taking LUMAKRAS®.
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If coadministration with an acid-reducing agent cannot be avoided, inform
patients to take LUMAKRAS® 4 hours before or 10 hours after a
locally acting antacid.
INDICATION
LUMAKRAS® is indicated for the treatment of adult patients with
KRAS G12C‑mutated locally advanced or metastatic non‑small cell lung
cancer (NSCLC), as determined by an FDA‑approved test, who have received at
least one prior systemic therapy.
This indication is approved under accelerated approval based on overall
response rate (ORR) and duration of response (DOR). Continued approval for
this indication may be contingent upon verification and description of
clinical benefit in a confirmatory trial(s).
Please see full LUMAKRAS®
Prescribing Information.
