Assessing Dermatologic Responses to Amivantamab in EGFR-Mutated NSCLC
The conundrum of treating dermatologic adverse effects in response to treatment with amivantamab for EGFR-mutated NSCLC was discussed in a recent Frontline Forum.
The panel of experts.
During the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, experts in the lung cancer space met to discuss updates presented at the conference, and how they will advance the field forward. The discussion focused on first- and second-line treatments in non–small cell lung cancer (NSCLC), implementation into the clinic, and adverse effect management.
The panel was led by Martin Dietrich, MD, PhD, a medical oncologist at Cancer Care Centers of Brevard, The US Oncology Network. He was joined by Wade T. Iams, MD, assistant professor of medicine in the Division of Hematology and Oncology at Vanderbilt University Medical Center; Helena A. Yu, MD, associate attending physician at Memorial Sloan Kettering (MSK) Cancer Center; Joshua K. Sabari, MD, assistant professor in the Department of Medicine at the NYU Grossman School of Medicine and director of High Reliability Organization Initiatives at the Perlmutter Cancer Center; and Solange Peters, MD, PhD, full professor and chair of medical oncology and the thoracic malignancies program in the Department of Oncology at the University Hospital of Lausanne in Switzerland.
The roundtable discussion was meant to draw ideas and thought-provoking questions from colleagues centered at different institutions around the world.
Biomarker Testing
Dietrich began by asking the panel to discuss their approaches to biomarker testing, liquid biopsies, and managing the logistics of testing. At Vanderbilt, Iams said he waits to begin treatment until the results from both the liquid and tissue biopsies have been returned.
Yu noted that she will send out both tissue and liquid biopsies but will wait until at least the tissue biopsy comes back before beginning treatment. MSK has in-house testing for liquid next-generation sequencing (NGS) and rapid testing for EGFR, ALK, and KRAS mutations.
Peters gave her thoughts from a European perspective and noted that reimbursement does not cover 2 different modes of testing.
“Tissue [testing] is mandatory for legal purposes and initial diagnosis, and adding the liquid is at the cost of the patient. [Liquid biopsy] is taken at resistance or in selected cases in the front line,” Peters said.
She went on to say her institution also has rapid testing, which is conducted to begin neoadjuvant treatment with a full NGS panel done to help determine later lines of therapy. Additionally, the turnaround time for NGS testing in Europe is about 1 week, which Peters believes is the reason why double testing is not reimbursed.
Dietrich and Sabari both do concurrent tissue and plasma testing up front. Sabari uses an in-house assay for tissue testing with a turnaround time of 14 to 21 days. Sabari sends the plasma to an outside vendor, with results being returned in about 5 days. He will then wait for the results before deciding on a treatment plan.
Important Trials to Note Surrounding EGFR-Mutated Disease
Converting Trial Data Into Clinic Use
Sabari was not convinced by the phase 3 FLAURA2 (NCT04035486) trial data and continues to use osimertinib (Tagrisso) monotherapy in the first-line setting. For patients who are high-risk, he would consider amivantamab (Rybrevant) plus lazertinib (Leclaza) if approved based on the PFS data from the FLAURA trial.
He would also consider a patient’s lifestyle before creating a treatment plan. Are they older or frail? Do they have children? Those who have a family may not be able to come to receive treatment every 2 weeks, so finding the right combination and regimens is important as well, he said.
For Peters, her treatment plans are based on evidence and data from clinical trials, as mandated by the laws in Europe. In Switzerland, where she practices, she is able to play with different combinations, as it is outside of European authority, but she does remain more conservative in her choices.
Iams added, “My general approach is osimertinib monotherapy for most patients. I’ve used the FLAURA2 [regimen] a couple times for 1 patient with symptomatic brain metastases at diagnosis and another patient with an atypical EGFR mutation, which wasn’t technically included in FLAURA2, but we can do those types of things where you just don’t feel as good about the osimertinib efficacy. Amivantamab I’ve used a handful of times and have not had good experiences. I have more often than not patients who end up in the [emergency department] because the infusion nurses are panicked with the infusion reactions.”
Dietrich was more open to using the treatment combinations, as he noted the need to work with the data available.
Yu mentioned the comfort she felt using a tyrosine kinase inhibitor (TKI) plus chemotherapy in the second-line setting. Her challenge is having 2 available treatment options for escalation and determining which one is appropriate for use.
Peters highlighted results from the phase 3 PALOMA-3 trial (NCT05388669), which assessed subcutaneous amivantamab vs intravenous treatment.5 She wondered whether the difference changed their treatment practice that much. As she noted, her nurses were used to treating and identifying infusion reactions.
Regarding deep vein thrombosis, Sabari said it was difficult to say that subcutaneous amivantamab was better than intravenous. Patients were also given prophylaxis on the study.
Sabari, who is working on the PALOMA-1 and -3 studies, believes subcutaneous formulation may be better tolerated. A biologic license application was recently submitted to the FDA for subcutaneous amivantamab in patients with EGFR-mutated NSCLC.6
Quality of life came into the discussion again, as the subcutaneous injection can be given in 5 minutes vs an all-day infusion. Sabari explained that it can be injected into any area of fat on the body, usually the stomach, with a butterfly needle.
Peters noted that the billing in Europe between intravenous and subcutaneous infusion would be the same, the increased costs may occur after time with the nurses.
Toxicity Management With Amivantamab
Most notable with amivantamab use has been the dermatologic toxicities. Patients can sometimes range from asymptomatic to desquamating dermatitis. Patients who have inflamed skin prior to starting treatment may have more of a reaction.
The phase 2 COCOON study (NCT06120140) is assessing how to reduce rash and paronychia related to amivantamab use for patients with EGFR-mutated NSCLC.7 Iams believes this study will be pivotal to help educate other clinicians on aggressive dermatologic management.
For Yu, the management of scalp and nail toxicity has proven to be the most challenging for her. She suggests the use of Loprox (ciclopirox) shampoo plus doxycycline if needed for infection. Additionally, patients may have to cut their hair short, which may impact their quality of life. For nail toxicity, she recommends antibiotics and vinegar soaks to mitigate discomfort.
Peters believes changes need to be implemented systematically. When she first began practicing, preventative antibiotics were given to try to mediate these toxicities to the more potent treatments being given.
Sabari finds when amivantamab is given in combination with a TKI, skin toxicity is observed. “Most of my [patients with] bad scalp toxicities that are grade 3/4 have been men who don’t tell us anything. They cover it, they put a hat on, and they just keep on going, and then they come in and it’s decimated,” he said.
Sabari will also recommend a dose hold to help with the toxicity. However, once a grade 2/3 scalp reaction occurs, it’s difficult to get it under control. He has admitted patients because of this.
Dietrich asked his colleagues whether scalp toxicities were noted in women as well. Both Yu and Sabari said the majority of patients with this are men. Yu has treated only 1 woman with this toxicity. Both Yu and Sabari believe it comes back to hygiene and how frequently patients wash their hair and the products they use to treat it.
Peters pointed out that this would be an appropriate time to work with dermatologists and figure out a good action plan. Yu agreed; especially for younger patients, clinicians may think it’s only a small rash, but for the patient, it can be more impactful than that.
Some patients may be experiencing severe symptoms but want to continue treatment because it’s helping their disease, noted Sabari. All around, education needs to to improve, and a collaborative team effort can help get treatment answers, he said.
One solution that has worked well for Peters in the past was creating a shampoo compound that included steroids and anti-
inflammatory agents.
Key Takeaways
As the conversation concluded, Dietrich asked the panel what their biggest takeaways from the ASCO meeting were. Iams was most excited about the subcutaneous amivantamab development.
Yu mentioned that an unmet need was better management for central nervous system and leptomeningeal disease, to which Sabari agreed. Sabari also highlighted how to best manage toxicities and how to decipher which patient will experience which toxicity, and whether it will be a benefit or risk to them.
References
- Ramalingam SS, Vansteenkiste J, Planchard D, et al. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med. 2020;382(1):41-50. doi:10.1056/NEJMoa1913662
- Planchard D, Jänne PA, Cheng Y, et al. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med. 2023;389(21):1935-1948. doi:10.1056/NEJMoa2306434
- FDA approves osimertinib with chemotherapy for EGFR-mutated non-small cell lung cancer. News release. FDA. February 16, 2024. Accessed June 18, 2024. https://bit.ly/49AeXjy
- Felib E, Chul Cho B, Gutérrez V, et al. Amivantamab plus lazertinib vs osimertinib in first-line EGFR-mutant advanced non-small cell lung cancer (NSCLC) with biomarkers of high-risk disease: A secondary analysis from the phase 3 MARIPOSA study. J Clin Oncol. 2024;42(suppl 16):8504. doi:10.1200/JCO.2024.42.16_suppl.8504
- Leighl NB, Hiroaki A, Sun Min L, et al. Subcutaneous amivantamab vs intravenous amivantamab both in combination with lazertinib, in refractory EGFR-mutated, advanced non-small cell lung cancer. J Clin Oncol. 2024; 42(suppl 17):LBA8505. doi:10.1200/JCO.2024.42.17_suppl.LBA8505
- Subcutaneous amivantamab biologics license application submitted to U.S. FDA for patients with EGFR-mutated non-small cell lung cancer. News release. Johnson & Johnson. June 17, 2024. Accessed June 18, 2024. https://tinyurl.com/ber349er
- Enhanced dermatological care to reduce rash and paronychia in epidermal growth factor receptor (EGRF)-mutated non-small cell lung cancer (NSCLC) treated first-line with amivantamab plus lazertinib (COCOON). ClinicalTrials.gov. Updated June 20, 2024. Accessed June 18, 2024. https://shorturl.at/37a5c
