A 57-year-old non-smoking Japanese woman presented with back pain, and chest radiography revealed diffuse bilateral opacities (Fig. 1A). Laboratory tests showed elevated CEA, SLX, and KL-6 levels, and chest computed tomography (CT) demonstrated innumerable ring-shaped ground-glass nodules (GGNs) with two 20-mm solid nodules in the left lower lobe (Fig. 1B). Transbronchial biopsy revealed non-mucinous adenocarcinoma with a micropapillary pattern (Fig. 1C), and PET/CT showed mild uptake (SUVmax 5.1) (Fig. 1D). Next-generation sequencing identified an EGFR exon 19 deletion, confirming stage IVB EGFR-mutated NSCLC presenting as extensive GGNs. Carboplatin–pemetrexed plus osimertinib (FLAURA2 regimen) was initiated. After one cycle, CT showed marked improvement (Fig. 1E, F), but diffuse GGNs and left lower lobe consolidation progressed after three cycles (Fig. 1G, H). Amivantamab plus lazertinib (MARIPOSA regimen) was then started. After five cycles, CT demonstrated substantial improvement in all pulmonary shadows, with reductions in CEA, SLX, and KL-6 levels (Fig. 1I, J). The patient remained clinically stable during MARIPOSA therapy, experiencing only grade 2 rash. Given that MET amplification, particularly in early progressors, and secondary EGFR resistance mutations are common mechanisms of resistance after FLAURA2 [1], and that MARIPOSA [2] has been reported to address these escape pathways [3], this sequential transition may have contributed to the marked tumor shrinkage observed. Notably, the response observed in this case to MARIPOSA exceeded that achieved with FLAURA2, underscoring its robust antitumor activity in EGFR-mutated NSCLC.
Patient clinical findings. Baseline radiography and CT revealed innumerable ring-shaped ground-glass nodules (GGNs) with two solid nodules in the left lower lobe (A, B). Transbronchial biopsy showed non-mucinous adenocarcinoma with a micropapillary pattern (C), and PET/CT demonstrated mild uptake (D). After one cycle of FLAURA2, GGNs and solid components improved (E, F), but progression occurred after three cycles (G, H). MARIPOSA therapy yielded marked improvement after five cycles (I, J). Laboratory trends are shown at right.
F.K. interpreted the data and drafted the original and revised manuscript. R.O. and M.K. were responsible for data curation. All authors have reviewed and approved the final version of the manuscript and agree to be accountable for their respective contributions to the work.
Ethical statementWe confirm that no animals were involved in this study. Written informed consent was obtained from the patient for the publication of this case report.
VerificationAuthors have seen the manuscript and agree to the content and data.
Patient consentObtained (Institutional Review Board approval was not required for case report. Instead, a consent form was obtained.)
Artificial intelligence involvementNo.
Funding sourceNo financial support was provided.
Conflict of interestThe authors have no conflicts of interest to declare.
The authors thank the patient for allowing the publication of this image.
