Studies Find Supportive Care Approaches for Amivantamab in Lung Cancer

Xiuning Le, MD, PhD

Associate Professor, Department of Thoracic/Head and Neck Medical Oncology

Division of Internal Medicine

The University of Texas MD Anderson Cancer Center

Houston, TX

This article is part 2 of a 2-part series from a Case-Based Roundtable event.

Targeted Oncology^TM: How did the MARIPOSA trial (NCT04487080) assess patients receiving amivantamab (Rybrevant) plus lazertinib (Lacluze) vs osimertinib (Tagrisso) forinterstitial lung disease (ILD)?

Xiuning Le, MD, PhD: I think it's based on both [scan and symptoms]. Nowadays, for ILD in most of the clinical trials, they will take our investigator report, and then they will also have a pulmonologist adjudication committee, so they will look at the scan and read the description of symptoms, and decide if this is ILD, if is pneumonia, or if it is progression.… Osimertinib causes ILD as well. For this regimen, I don't think ILD is my worry. I feel like the incidence is at the baseline.

What is your experience managing the infusion reaction associated with amivantamab?

When amivantamab was first approved in the EGFR exon 20 space, I heard a lot of pushback about the infusion reaction. Patients had a bad experience and got very scared. I talk to the patients about the infusion reaction before the first 2 doses back-to-back [on day 1 and day 2, but I feel like my treatment nurses are very familiar [with it]. They're no longer calling me as frequently. The call is almost always related to [when] the clinic is closing, [and they ask whether we] can we do tomorrow's part with more treatment. It becomes logistical. I don't know how much the infusion reaction is still a…barrier if you're going to try it. I think as a field we’ve moved beyond the infusion reaction issue.

For the infusion reaction, there is a clinical trial run by Janssen's team called the SKIPPirr trial [NCT05663866]. I think this trial is very patient oriented. They're trying to see what we can do to decrease the rate of infusion reaction. They started with 4 different potential measures, including moderate-dose vs a higher-dose dexamethasone, and then 2 other medicines. Then they moved on to stage 1 [with a goal of] decreasing infusion reaction in half [of treated patients]. Then in stage 2, they continued [treating with the regimens that were] able to decrease infusion reaction.

With the SKIPPirr trial, the conclusion is that dexamethasone 8 mg given twice daily 2 days before [amivantamab], basically 4 doses, and then an IV infusion on the day of treatment, is the one that they recommended going forward.¹ They were able to decrease infusion reactions from [over] 65% to 22%, so it's a significant benefit. What is interesting enough to me is that dexamethasone at 4 mg was not enough. You have to do 8 mg to reverse that process. Currently, if I start anybody on amivantamab, either in the front line or as subsequent treatment, I do this. I feel like this is straightforward and simple enough that if that can save the patient the hassle of getting the infusion reaction and additional hydrocortisol, this is already part of our treatment plan.

What other tolerability issues do you face with this regimen?

The second challenge I think most of us are more feeling annoyed by is the dermatological issue, because most of the high-grade toxicities are skin rash. This is also the most common reason to interrupt treatment and have to discontinue or do dose reduction. Any grade 2 and higher skin toxicity is a major problem and an inconvenience for patients. Overall, during the trial management, we all recommended proactive treatment for skin rash at the initial skin rash, educating the patient, and providing oral antibiotics and topical antibiotics.

Again, one of the things that the Janssen team did to help patients’ quality of life is they had a clinical trial [COCOON (NCT06120140)] that enrolled 180 patients and then tried to intensify their skin rash [management] vs the regular standard of care.

I want to go over this regimen, because this study is positive, meaning that if someone follows this set of skincare regimens, a patient's grade 2 and higher rash can be decreased and then can be a lot more manageable.² It’s relatively simple and cheap. It's a prophylactic antibiotic, oral doxycycline or minocycline starting from day 1. This is almost prophylactic to start, but we know that with amivantamab/lazertinib, many patients have a rash, so I think that's important. [They also] started with topical clindamycin 1%. I think a lot of us already do that. They want us to do this for the first few weeks, 12 or more weeks, so that the patient can get as much initially [so] the skin is calm and not going to grade 2 or grade 3.

For paronychia, they have the chlorhexidine 4% solution. They also asked for skin moisturizer. Initially, they recommended one brand that's globally available, but in the subsequent report they recommended something generic and cheap.

With this regimen, I will say it's not too complicated for patient to start at the cycle 1 day 1. The results are not available, but a press release said this trial is positive, so it's good for patients’ benefit going forward.²

What is your experience with these strategies?

In a few clinical trials I have run, including even earlier-generation tyrosine kinase inhibitors [TKIs] like poziotinib, and currently there are [trials of] high-dose intensity TKI, [I have used] the first 2 oral antibiotics. I automatically prescribe for 2 weeks of supply and then refill, and then I ask them to take home clindamycin 1%. For paronychia and the skin moisturizer, I educate them that they should just [use it] at least twice a day. The only thing I don't do prophylactically is for paronychia. For amivantamab, if I start, I will try to do it. For me, my nurse can get a printout and instruct them what to do.

DISCLOSURES: Le previously reported consulting/advisory role for Eli Lilly, EMD Serono, AstraZeneca, Spectrum Pharmaceutics, Novartis, Regeneron, Boehringer Ingelheim, Hengrui Therapeutics, Bayer, Teligene, Taiho, Daiichi Sankyo, Janssen, Blueprint Medicines, Sensei Biotherapeutics, SystImmune, ArriVent, Abion, and AbbVie; institutional research funding from Eli Lilly, EMD Serono, ArriVent, Dizal, Teligene, Regeneron, Janssen, ThermoFisher, Takeda, and Boehringer Ingelheim; travel support from EMD Serono, Janssen, and Spectrum Pharmaceutics, and stock options from BlossomHill.

_REFERENCES:

_{1. Paz-Ares LG, Spira AI, Han J-Y, et al. Preventing infusion-related reactions with intravenous amivantamab: Updated results from SKIPPirr, a phase II study. Ann Oncol. 2024;35(suppl 2):S812. doi:10.1016/j.annonc.2024.08.1326}

_{2. COCOON study meets primary endpoint demonstrating statistically significant and clinically meaningful reduction in dermatologic reactions with easy-to-use prophylactic regimen for patients with EGFR-mutated NSCLC. News release. Johnson & Johnson Innovative Medicine. January 14, 2025. Accessed May 15, 2025. https://tinyurl.com/resmspzb}