Stephen Liu, MD, Discusses the COCOON Study

Stephen V. Liu, MD, of the Georgetown University School of Medicine and Georgetown’s Lombardi Comprehensive Cancer Center in Washington, DC, joined Lung Cancers Today to discuss the recent announcement that the COCOON study met its primary endpoint.

The randomized phase 2 study is evaluating a prophylactic dermatologic regimen to reduce the incidence of skin and nail adverse reactions in patients receiving first-line treatment with amivantamab plus lazertinib.

“COCOON looked at a preventative and proactive support strategy to minimize toxicity,” Dr. Liu said. “It’s a patient-first approach, one that I applaud.”

The study includes 200 patients with newly diagnosed locally advanced or metastatic non–small cell lung cancer (NSCLC) with EGFR exon 19 deletions or L858R substitution mutations. Patients were divided into two groups, with one group receiving an “enhanced dermatologic care regimen designed to prevent skin and nail adverse reactions,” and the other receiving standard dermatologic care.

The enhanced dermatologic regimen involves taking oral doxycycline or minocycline, 100 mg, twice daily for weeks 1 through 12, then using 1% topical clindamycin lotion on the scalp daily before bedtime for weeks 13 through 52. For weeks 1through 52, patients also wash hands and feet once daily with 4% chlorhexidine and apply a ceramides-based moisturizer to the body and face at least once daily.

“The thought here is that [using] these interventions upfront—early, before patients developed dermatologic toxicities—would reduce the incidence and severity of certain adverse events related to this regimen,” Dr. Liu said.

The interim analysis demonstrated that the enhanced regimen significantly reduced the frequency of grade 2 or higher skin and nail adverse reactions and the severity of skin-related side effects compared with standard dermatologic management for patients receiving first-line treatment with amivantamab and lazertinib.

“This was a positive intervention,” Dr. Liu said. “This is a relatively low-cost, upfront intervention, one that we’d like to see more of.”

The phase 3 MARIPOSA trial demonstrated that the combination of amivantamab plus lazertinib has a progression-free survival and overall survival benefit over osimertinib, but it’s important to recognize how efficacy and toxicity interplay to create the therapeutic window.

“When we’re adding more drugs, we will add toxicity. The question is how much more efficacy will we see relative to that toxicity?” Dr. Liu said. “To widen that therapeutic window, we can either further increase the efficacy, which we always want to do, or we can decrease the toxicity, which we also would like to do. That latter approach, though, is not focused on as much as we’d like.”

With these results being shared via a press release and full data to be presented at an upcoming medical conference, Dr. Liu explained that questions remain about the details, including the specific adverse events that were helped with this approach, the level of improvement, and if certain patients had a greater benefit from the therapy.

“I look forward to seeing these data presented in their full entirety,” Dr. Liu said.