COCOON study

One of the highlights of ELCC 2025 consisted of the overall survival (OS) results of the MARIPOSA study. These data showed that the combination of lazertinib and amivantamab in the first line treatment of EGFR-mutant non-small-cell lung cancer (NSCLC) patients resulted in a significantly longer OS compared to the current standard of care (i.e., osimertinib monotherapy). However, this OS benefit did come at the cost of increased toxicity, with, among others, a high incidence of grade ≥2 dermatological adverse events (AEs). To mitigate the toxicity burden that comes with lazertinib-amivantamab several preventive strategies have been developed. In this respect, ELCC 2025 also featured the primary results of the phase II COCOON study, evaluating an elaborate dermatological prevention regimen in EGFR-mutant, advanced NSCLC patients receiving a combination of lazertinib-amivantamab. In this video, Prof Nicolas Girard, thoracic oncologist at the Institut Curie in Paris, shares the key results of this presentation.

In the randomized, phase II COCOON study, 138 EGFR-mutant NSCLC patients initiating a treatment with lazertinib-amivantamab were randomly assigned to local standard of care for dermatological AEs and a dermatological prevention strategy consisting of oral doxycycline/minocycline (100 mg BID, weeks 1–12), clindamycin 1% lotion on the scalp (QD, weeks 13–52), chlorhexidine 4% to wash hands & feet (QD), & non-comedogenic ceramide-based moisturizer to use on the body & face (QD). Early results of COCOON showed that this preventive strategy was associated with a 50% reduction in the incidence of grade ≥2 dermatological AEs at week 12 (from 76.5% to 38.6%). Importantly, the impact of the preventive strategy was seen on all locations, with a 65% reduction in the incidence of grade ≥2 dermatological AEs on the face and body (from 62% to 23%), a 70% reduction in grade ≥2  dermatological events on the scalp (from 29% to 9%) and a 25% reduction in the incidence of grade ≥2 paronychia (from 21% to 16%). Furthermore, the preventive strategy led to a reduction in the need for dose interruption (16% vs. 34%), dose reduction (7% vs. 19%) and treatment discontinuation (1% vs. 4%). 

In conclusion, the prophylactic COCOON regimen, with widely available and easy-to-use agents, significantly reduces the incidence and severity of dermatologic AEs with amivantamab + lazertinib and should therefore be part of the routine management of patients planned for this treatment. In addition to this, patients should be given prophylactic anticoagulation to reduce the risk for thromboembolic events and receive dexamethasone to mitigate the risk for infusion-related reactions.