Safety Profile
Warnings and Precautions for RYBREVANT® + carboplatin and pemetrexed (N=151)
Infusion-related reactions (IRRs)1
RYBREVANT can cause infusion-related reactions (IRR); signs and symptoms of IRR include dyspnea, flushing, fever, chills, nausea, chest discomfort, hypotension and vomiting.
Based on the safety population of PAPILLON, IRRs occurred in 42% of patients treated with RYBREVANT® + chemotherapy, including Grade 3 (1.3%) adverse reactions (ARs). The incidence of infusion modifications due to IRR was 40%, and 0.7% of patients permanently discontinued RYBREVANT®.
In the PAPILLON trial, most IRRs occurred during the first infusion (Week 1, Day 1) and rarely during subsequent infusions2
- 98.7% of IRRs were Grades 1-21,2
- Median time to onset of first IRR was 0.8 hours (range 0.1-3.6)2
- Monitor patients for any signs and symptoms of infusion-related reactions during RYBREVANT® infusion. Interrupt infusion if IRR is suspected. Reduce the infusion rate or permanently discontinue RYBREVANT® based on severity1
IRRs are common; most occur during the first infusion and can be managed through Premedications
Interstitial Lung Disease/Pneumonitis1
RYBREVANT® can cause interstitial lung disease (ILD)/pneumonitis. Based on the safety population, Grade 3 ILD/pneumonitis occurred in 2.6% of patients treated with RYBREVANT® + chemotherapy; all patients required permanent discontinuation.
Dermatologic Adverse Reactions1
RYBREVANT® + chemotherapy can cause dermatologic ARs, such as rash (including dermatitis acneiform), pruritus and dry skin. Based on the safety population of PAPILLON, rash occurred in 89% of patients treated with RYBREVANT® + chemotherapy, including Grade 3 ARs (19%). Rash leading to dose reductions occurred in 19% of patients; 2% permanently discontinued RYBREVANT®, and 1.3% discontinued pemetrexed.
Ocular Toxicity1
RYBREVANT® + chemotherapy can cause ocular toxicity including keratitis, dry eye symptoms, conjunctival redness, blurred vision, visual impairment, ocular itching, and uveitis. Based on the safety population of PAPILLON, RYBREVANT® + chemotherapy can cause ocular toxicity including blepharitis, dry eye, conjunctival redness, blurred vision, and eye pruritus. All events were Grades 1-2.
Embryo-Fetal Toxicity1
Based on its mechanism of action and findings from animal models, RYBREVANT® can cause fetal harm when administered to a pregnant woman. Administration of other EGFR inhibitor molecules to pregnant animals has resulted in an increased incidence of impairment of embryo-fetal development, embryo lethality, and abortion. Advise females of reproductive potential of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of RYBREVANT®.
For Warnings and Precautions for RYBREVANT® as a single agent, please see sections 5.1-5.5 of the Prescribing Information.
Safety profile of PAPILLON
The majority of adverse reactions (ARs) were Grades 1 and 21
Adverse reactions (≥10%) observed in the PAPILLON clinical study.
*Adverse reactions were graded using CTCAE version 5.0.
†Grouped terms.
- Serious adverse reactions occurred in 37% of patients who received RYBREVANT® + chemotherapy compared with 31% of patients who received chemotherapy alone. Serious adverse reactions in ≥2% of patients included rash, pneumonia, ILD, pulmonary embolism, vomiting, and COVID-191,3
- The most common ARs (≥20%) were rash, nail toxicity, stomatitis, infusion-related reaction, fatigue, edema, constipation, decreased appetite, nausea, COVID-19, diarrhea, and vomiting
- Clinically relevant adverse reactions in <10% of patients who received RYBREVANT® + chemotherapy included pulmonary embolism, deep vein thrombosis, skin ulcer, conjunctivitis, and ILD/pneumonitis1
CTCAE, Common Terminology Criteria for Adverse Events.
Summary of laboratory abnormalities (≥20%) in PAPILLON1
*Adverse reactions were graded using CTCAE version 5.0
†The denominator used to calculate the rate varied from 113 to 150 based on the number of patients with a baseline value and at least one post-treatment value.
‡The denominator used to calculate the rate varied from 119 to 154 based on the number of patients with a baseline value and at least one post-treatment value.
Grade 3 to 4 laboratory abnormalities (≥ 2%) were decreased albumin, increased alanine aminotransferase, increased gamma glutamyl transferase, decreased sodium, decreased potassium, decreased magnesium, and decreases in white blood cells, hemoglobin, neutrophils, platelets, and lymphocytes1
~90% of patients treated with RYBREVANT® were able to stay on treatment without AR-related discontinuation1
Permanent discontinuation of RYBREVANT® due to ARs occurred in 11% of patients1
Adverse reactions resulting in permanent discontinuation of RYBREVANT® in ≥1% of patients were rash and ILD.
Dose interruptions of RYBREVANT®1
Dose interruption due to an adverse reaction occurred in 64% of patients. Adverse reactions requiring dose interruption in ≥5% of patients included rash and nail toxicity.
Infusion interruptions of RYBREVANT®1
Infusion-related reactions (IRR) requiring infusion interruptions occurred in 38% of patients.
Dose reductions of RYBREVANT®1
Dose reductions due to an adverse reaction occurred in 36% of patients. Adverse reactions requiring dose reductions in ≥5% of patients included rash and nail toxicity.
See Dosage & Administration for AR monitoring/management and dose modification information.
Proactive supportive care for RYBREVANT® is recommended1
Proactive supportive care was not mandatory in the PAPILLON study. Some recommendations are based on the clinical trial experience while others are from guidelines.
AR, adverse reaction; EGFR, epidermal growth factor receptor; NSCLC, non-small cell lung cancer.
Proactive supportive care can help reduce the risk and severity of dermatologic ARs associated with EGFR-targeted therapies
Use of prophylactic antibiotics (with or without topical skin therapies) have demonstrated6*:
Multinational Association of Supportive Care in Cancer (MASCC) guidelines recommend proactive measures (Weeks 1-6) to reduce the risk of severe reactions.7†
Based on the high frequency of rash in EGFR inhibitor–treated patients and the consistent presentation within the first 2-4 weeks of therapy, preventive/prophylactic management is recommended unless there are contraindications based on patient and/or healthcare provider factors.7
*Based on a systematic review and meta-analysis of 13 studies including 1,073 patients.6
†The rash indicated is papulopustular (acneiform rash).
AR, adverse reaction; EGFR, epidermal growth factor receptor; NSCLC, non-small cell lung cancer.
Proactive lifestyle approach for dermatologic adverse reactions
Throughout treatment, it is important to advise patients1:
Based on RYBREVANT® Prescribing Information.
Communicating these tips with patients may help reduce the risk and severity of dermatologic adverse reactions8
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See the recommended dosage, administration, and dose modification information.
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References
1. RYBREVANT® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
2. Data on file. Janssen Biotech, Inc.
3. Zhou C, Tang K-J, Cho BC, et al; PAPILLON Investigators. Amivantamab plus chemotherapy in NSCLC with EGFR exon 20 insertions. N Engl J Med. 2023;389(22):2039-2051.
4. Yin X, Zhao Z, Yin Y, et al. Adverse event profiles of epidermal growth factor receptor-tyrosine kinase inhibitors in cancer patients: a systematic review and meta-analysis. Clin Transl Sci. 2021;14(3):919-933.
5. Hofheinz RD, Deplanque G, Komatsu Y, et al. Recommendations for the prophylactic management of skin reactions induced by epidermal growth factor receptor inhibitors in patients with solid tumors. Oncologist. 2016;21(12):1483-1491.
6. Petrelli F, Borgonovo K, Cabiddu M, et al. Antibiotic prophylaxis for skin toxicity induced by antiepidermal growth factor receptor agents: a systematic review and metaanalysis. Br J Dermatol. 2016;175(6):1166-1174.
7. Lacouture ME, Anadkat MJ, Bensadoun RJ, et al. Clinical practice guidelines for the prevention and treatment of EGFR inhibitor-associated dermatologic toxicities. Support Care Cancer. 2011;19(8):1079-1095.
8. Chan JC, Lee YH, Liu CY, et al. A correlational study of skin toxicity and quality of life in patients with advanced lung cancer receiving targeted therapy. J Nurs Res. 2019;27(6):e51.
