Lung Cancer Drug Combo Tolerability Boosted by Proactive Skin Care
New Regimen Significantly Reduces Adverse Effects in NSCLC Patients
A groundbreaking study is offering a potential solution to debilitating skin reactions experienced by patients undergoing treatment for non-small cell lung cancer (NSCLC), improving their quality of life and treatment adherence.
Targeting Dermatologic Side Effects
The combination of amivantamab-vmjw (Rybrevant) and lazertinib (Lazcluze) has shown remarkable efficacy in treating NSCLC, but its accompanying dermatologic adverse effects (AEs) have often presented significant challenges for patients. Investigators of the phase 2 COCOON trial (NCT06120140) sought to alleviate these issues by implementing a comprehensive dermatologic management strategy.
COCOON Trial Demonstrates Success
Results presented at the European Lung Cancer Congress 2025 revealed that patients receiving amivantamab plus lazertinib alongside an enhanced dermatologic regimen experienced a notable decrease in skin-related AEs. This proactive approach, initiated at the start of treatment, included oral doxycycline or minocycline, clindamycin, chlorhexidine, and a ceramide moisturizer.
Alexander I. Spira, MD, PhD, FACP, FASCO, a leading oncologist, discussed the trial’s findings with Randi Rabin, MSc, MPH, PA-C, emphasizing the shift in oncology from solely focusing on survival data to actively managing patient tolerability and quality of life (QOL).
The COCOON trial enrolled patients with newly diagnosed, advanced, or metastatic NSCLC who had specific EGFR mutations. Participants were divided into two groups: one receiving amivantamab plus lazertinib with the enhanced dermatologic management (COCOON DM, n = 99), and the other receiving the same drugs with standard dermatologic care (SOC DM, n = 102).
The COCOON DM regimen involved 100 mg of oral doxycycline or minocycline daily for 12 weeks, coupled with topical 1% clindamycin on the scalp daily. Additionally, patients used 4% chlorhexidine on nails daily for 12 months and a ceramide-based moisturizer on the face and body at least daily for the same duration. The standard of care group received general skin prophylaxis based on local practices and reactive treatments.
Grade 2 or higher AEs occurred in 38.6% of patients in the COCOON DM arm, compared to 76.5% in the SOC DM arm. Grade 3 AEs were reported in 4.3% of the enhanced management group versus 8.8% in the standard care group, a statistically significant difference (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].”
—Alexander I. Spira, MD, PhD, FACP, FASCO
The difference in dose modifications due to dermatologic AEs was also stark: dose interruptions occurred in 16% of COCOON DM patients versus 34% of SOC DM patients, dose reductions in 7% versus 19%, and discontinuations in 1% versus 4%. These results suggest the enhanced regimen significantly reduces the need for treatment adjustments.
Implementing a Proactive Approach
Randi Rabin highlighted the positive patient reception and adherence to the COCOON DM regimen, noting that the proactive management has been transformative. She stressed the importance of initiating these preventative measures before AEs become severe.
The study’s success underscores the need for clinicians to adopt a proactive strategy, not waiting for skin issues to manifest before intervening. The use of clindamycin lotion, for example, has proven more effective and convenient than previous topical treatments. Integrating ceramide moisturizers is also crucial for skin barrier restoration and reducing inflammation.
Spira emphasized the value of a standardized approach to managing dermatologic AEs associated with amivantamab/lazertinib therapy, stating, “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…”
Enhancing Patient Education and Support
The importance of a multidisciplinary approach and robust patient education was also a key takeaway. Providing patients with clear, accessible information about potential AEs and the recommended management strategies empowers them to actively participate in their care.
Rabin suggested that streamlined implementation, including pre-built order sets and patient education sheets, would further support healthcare providers. “Overall, a standardized supportive care tool kit that we can share with these patients would be extraordinarily helpful,” she stated.
This proactive and supportive care model not only aims to mitigate AEs but also fosters a stronger patient-provider relationship, encouraging open communication about treatment experiences. By empowering patients with knowledge, this approach can lead to better treatment adherence and improved outcomes.
