COCOON Regimen Shows Promise in Mitigating Dermatologic AEs During NSCLC Treatment

The panel.

The regimen of amivantamab-vmjw (Rybrevant) plus lazertinib (Lazcluze) is known to have dermatologic adverse effects (AEs) that can make staying on treatment a challenge. Investigators in the phase 2 COCOON trial (NCT06120140) set out to find a way to mitigate dermatologic AEs that patients with non–small cell lung cancer (NSCLC)may experience when receiving the regimen.1,2

Results from COCOON presented earlier this year at the European Lung Cancer Congress 2025 showed that the use of oral doxycycline or minocycline, clindamycin, chlorhexidine, and ceramide moisturizer, given immediately when starting treatment, showed a decrease in dermatologic AEs.

Alexander I. Spira, MD, PhD, FACP, FASCO, codirector of the Virginia Cancer Specialists (VCS) Research Institute, director of the VCS Thoracic and Phase I Program, chief scientific officer of NEXT Oncology, and clinical assistant professor at Johns Hopkins University School of Medicine, spoke with Randi Rabin, MSc, MPH, PA-C, of VCS, regarding the results and implementation of the regimen into clinical practice.

COCOON Trial

Spira noted that the oncology community has long focused on survival data and is now pivoting to managing AEs. He also mentioned the treatment’s tolerability and the need to get patients to benefit from it.

COCOON enrolled patients with newly diagnosed, locally advanced, or metastatic NSCLC with EGFR exon 19 deletion or L858R substitutions. Patients were given either amivantamab plus lazertinib and the enhanced dermatologic management (n = 99; COCOON DM) or amivantamab plus lazertinib and the standard dermatologic management (n = 102; standard of care [SOC] DM).

The COCOON DM regimen consisted of oral doxycycline or minocycline at 100 mg by mouth for 12 weeks with follow-up by topical 1% clindamycin daily on the scalp; 4% chlorhexidine on the fingernails and toenails daily for 12 months; or ceramide -based moisturizer on the body and face at least daily for 12 months. The SOC DM regimen included general skin prophylaxis determined by local practice and reactive treatments like topical corticosteroid and systemic antibiotics. Rabin noted she has not had any adherence issues among her patients taking the COCOON DM regimen.

Grade 2 or higher AEs were observed in 38.6% of patients in the COCOON DM regimen and 76.5% in the SOC DM regimen. Grade 3 AEs were observed in 4.3% vs 8.8%, respectively (OR, 0.19; 95% CI, 0.09-0.40; P <.0001).

“Grade 2 is still a significant part of your body with a rash; it’s still happening but at a much lower frequency. Grade 3 is where it makes us nervous. That’s where we start to think about how dose holds affect the quality of life [QOL],” Spira said. “[The results are] clearly statistically significant as well, with an OR of 0.19. That’s as good as you’ll ever get in any oncology study.”

Dermatologic AEs by location that were grade 2 or higher in the COCOON DM and SOC DM arms included face/body excluding the scalp (23% vs 62%), scalp (9% vs 29%), and paronychia (16% vs 21%). Rabin noted that scalp toxicity is difficult to manage, especially when it becomes infected. This AE has caused dose holds, reductions, and even discontinuations from amivantamab/lazertinib treatment. Amivantamab or lazertinib led to dose modifications from dermatologic AEs, including dose interruption (16% vs 34%), dose reduction (7% vs 19%), and discontinuation (1% vs 4%), whereas any AEs led to dose interruption (50% vs 54%), dose reduction (21% vs 31%), and discontinuation (11% vs 19%) between both arms, respectively.

For Spira, this study had 2 foci: Can QOL be improved, and can patients be kept on treatment longer? He also highlighted that most of these AEs are experienced within the first 12 weeks of treatment, so if patients get through that, they will be able to experience more of a benefit.

Initially, Spira was worried about the strain this regimen would put on patients. While they were taking amivantamab plus lazertinib, they were also instructed to treat these dermatologic AEs. At the time, he wondered whether this was worth it.

“One of the most challenging aspects of using amivantamab and lazertinib is the high rate of dermatologic and nail toxicity, which can affect QOL and treatment adherence. Now we’re seeing a meaningful reduction of grade 2 and higher AEs. This proactive, supportive care protocol validates what we as health care providers have been trying to do for a long time…start these methods early to prevent these AEs. Patients are being quite receptive to it,” Rabin said.

Adjusting Practice for the COCOON DM Regimen

These data cement that clinicians should not wait for a rash to appear before giving treatment. Rabin now has patients use the chlorhexidine wash on their fingernails and toenails, and it has helped with paronychia and granuloma tissue.

The use of clindamycin lotion has also been a game changer. Previously, an antibiotic ointment was prescribed, but it was sticky and difficult to apply. Additionally, adding ceramide moisturizers to help combat dry skin is “super important,” according to Rabin, as it will restore the skin barrier and decrease inflammation caused by treatment.

Prior to clindamycin lotion, Spira was telling patients to use steroid shampoos, but clindamycin is the go-to regimen. The COCOON DM regimen signified to Spira that there is a standard way to approach dermatologic AEs related to amivantamab/lazertinib treatment.

Seeing her patients every 2 weeks is essential practice for Rabin. She likes to see how they are doing with the treatment and assess whether it is impacting their QOL. She also tells her patients to alert her or her team if scalp, nail, or skin changes occur. She also has them check their scalp multiple times a week.

Spira emphasized creating that relationship with patients so they will confide about their AEs. Often, patients will not mention them until they have become bad, so the key is to educate before treatment on what to look for and how to manage it.

Multidisciplinary Team Care and Standardizing Practice

For academic or community centers that may not have an available in-house oncodermatology team, Spira prefers not to refer patients to an external dermatologist. Often, a rash or other dermatologic AE will get biopsied or treated when it is related to the amivantamab/lazertinib treatment. Additionally, patients may be seeing a pulmonologist and their internist, and coming to the cancer center multiple times a week, which can add up to a lot of co-pays.

Rabin agrees with this practice. She noted that some patients may seek a podiatrist for help with the granuloma tissue.

“In terms of additional support that we may benefit from, streamlining the implementation of the COCOON regimen [should include] prebuilt order sets for prophylactic oral and topical antibiotics that can help minimize AEs, plus having a patient education sheet that we can hand out to patients, with the AEs to look out for: ‘Here’s the regimen that we’re recommending that you can follow to help reduce some of these AEs,’” Rabin said. “Overall, a standardized supportive care tool kit that we can share with these patients would be extraordinarily helpful.”

Spira highlighted the helpfulness of the printed education sheet, as there is a difference between the older and younger generations and how they process information. He also suggested uploading it to the electronic health records as a backup.

Overall, Rabin believes patients are excited to be educated on what to do up front to help mitigate these dermatologic AEs. She highlighted that this is “a knowledge that empowers them.” Most patients have been open and accepting of treatment, and she has not received pushback on the regimens.

Take-Home Messages

Rabin noted that clinicians and patients should meet before day 1 of treatment to review the AEs they may experience. She also highlighted the need not to wait for issues to appear but to start the education and awareness surrounding them early.

“This is one of the first few studies where I’ve seen a proactive management making a difference in outcomes, and it’s going to change how I approach when I use other EGFR inhibitors, or anything that might be causing a rash, or I know that’s high in the risk of AEs,” Spira said. “It does appear that you can be more proactive, and patients will do better, and that’s not how we usually thought in the past. I’m going to try to think about this in my practice as well.”

Reference

1. Girard N, et al. Preventing moderate to severe dermatologic adverse events in first-line EGFR-mutant advanced NSCLC treated with amivantamab plus lazertinib: early success of the COCOON trial. European Lung Cancer Congress 2025; March 27, 2025; Paris, France. Abstract 10MO.
2. Easy-to-use preventative regimen demonstrates a statistically significant and clinically meaningful reduction in dermatologic reactions in patients with EGFR-mutated NSCLC. News release. Johnson & Johnson. March 27, 2025. Accessed May 29, 2025. https://tinyurl.com/ybrvswbt