[Madrid, Spain = E-Daily Reporter Kim Jinsoo ] “In the combination therapy of Lecraz and Librivant, most skin-related side effects occurred predominantly during the initial 12 weeks—that is, within the first three months—of treatment. Once this period has passed, both doctors and patients can continue treatment for a longer period. I believe the results of this study will help reduce the rate of treatment discontinuation.”

Professor Cho Byung-chul of Yonsei Cancer Hospital stated in an interview with PharmDaily at the European Society for Medical Oncology (ESMO) conference in Madrid, Spain, “The most important point of this study is that side effects are reduced with the combination of Lecraza and Libravant. When side effects are reduced, patients’ quality of life improves.”

Skin-related side effects are a common adverse reaction to EGFR-targeted therapies and are considered a major factor hindering the continuation of combination therapy. Severe skin toxicity not only lowers patients’ quality of life but can also lead to dose reductions or treatment discontinuation, posing an obstacle to maintaining stable treatment efficacy.

In fact, according to the U.S. prescribing information for Libravant—a drug used in combination with the lung cancer treatment Yuhan(000100) Lecraza—the incidence of rash in the combination group was 86% in the MARIPOSA study, which used the intravenous (IV) formulation. The rate of temporary discontinuation of Libravant due to rash was 37%, and the rate of permanent discontinuation was 5%. In other words, the occurrence of side effects, along with treatment efficacy, is a key factor in determining whether patients can continue taking the medication.

Professor Cho presented the results of a new cohort from the “COCOON” study—which evaluated strategies for preventing skin side effects associated with the combination therapy of Lecraza and Libravant—at the European Society for Medical Oncology (ESMO 2026) conference held in Madrid, Spain.

This new cohort study included 104 patients with EGFR-mutated advanced non-small cell lung cancer. The 70 patients in the standard-schedule group received the combination of Lecraza and Libravant via subcutaneous (SC) injection from the start, while the 34 patients in the pre-treatment group first took Lecraza for one cycle (4 weeks) before adding Libravant. Both groups were treated with a simplified skin adverse reaction prevention regimen involving oral antibiotics and moisturizers.

According to the study, the incidence of Grade 2 or higher skin adverse events within 12 weeks of treatment initiation was 39% in the standard-schedule group and 18% in the lead-in group. Grade 3 or higher events were 3% and 0%, respectively. In an exploratory analysis at week 16 of the pre-treatment group, the incidence rate of Grade 2 or higher adverse events was 24%, and no Grade 3 or higher events were observed. In the initial analysis, the investigator-assessed objective response rate was 71% and 70% in the two groups, respectively. During the same 12-week period, the rate of permanent discontinuation of Libravant due to skin adverse events was 1% in the standard schedule group and 0% in the pre-treatment group.

Professor Cho explained, “Further confirmation is needed to determine why side effects are less frequent when Lecraza is administered first. If both drugs are administered together from the start, side effects can easily occur due to synergistic effects between the two. However, we can hypothesize that delaying the start of combination therapy by one month relatively reduces overlapping side effects.”

He also viewed the approach of administering Lecraz first positively, noting that it allows for a stepwise treatment regimen in actual clinical practice.

Professor Cho stated, “There is a lot to prepare when starting treatment for the first time. Since it is difficult to complete everything in a single day, patients can learn how to manage side effects on their own while taking Lecraza for a month and have time to adapt to the treatment.” He added, “Reflecting real-world clinical practice, the key message is that simply changing the timing of administration significantly reduces side effects and improves patient convenience, while efficacy is well maintained without any significant changes.”

He continued, “In the group that received Lecraza first, no Grade 3 side effects occurred, and most were managed within Grade 2 or lower,” adding, “This means it is highly likely that not only will the incidence rate decrease, but the severity experienced by patients will also decrease.”

The fact that preventive therapy can be adapted into a form that is easier for patients to follow, thereby enhancing their convenience, is also a key factor in ensuring treatment adherence.

The previous COCOON randomized trial utilized oral antibiotics, moisturizers, topical antibiotics applied to the scalp, and nail and foot disinfectants. In contrast, this study simplified the regimen to using antibiotics for approximately 12 to 24 weeks and applying moisturizers, which proved to be sufficiently effective.

Professor Cho stated, “It is significant that pre-treatment with Lecraza gave patients time to learn how to manage skin-related side effects on their own and enabled them to self-manage in their daily lives through simple preventive measures.”

Professor Cho assessed that this shift is part of a process that enhances the competitiveness of combination therapy. He explained, “Since Tagrisso is used in combination with chemotherapy, side effects such as anemia or leukopenia are more of a concern than skin-related side effects. While a direct comparison is difficult, it is fair to say that Lecraza is gradually evolving into a more competitive treatment option.”

Finally, Professor Cho stated, “Continuing treatment for a long time does not simply mean taking the medication for a long time; it means that it becomes a key driving force for maintaining efficacy.”