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Lung Cancer Treatments and Mutations / Lung Cancer Diagnosis and Treatment / HER2/EGFR in Cancer Research · Journal article
Frontiers in Oncology · August 10, 2026
Early or partial results. Treat as a signal, not a conclusion.
This is a single case report of a HER2-mutant lung adenocarcinoma patient who achieved 14 months of progression-free survival with T-DXd rechallenge after documented disease progression on prior T-DXd and intervening chemotherapy, without recurrence of interstitial lung disease. The authors propose T-DXd rechallenge as a potential option in carefully selected patients when alternatives are limited, but explicitly acknowledge that prospective and real-world cohort evidence is needed to validate this approach.
Case report. Female patient with HER2-mutant (exon 20) lung adenocarcinoma who had received multiple lines of chemotherapy and prior T-DXd.. Intervention: Trastuzumab deruxtecan (T-DXd) rechallenge administered systemically along with local embolization..
Patient with HER2 exon 20 mutation achieved prolonged disease control during T-DXd rechallenge (progression-free survival 14 months) Rechallenge was administered systemically along with local embolization and provided clinical benefit despite prior radiographic progression on T-DXd No recurrence of interstitial lung disease (ILD) during rechallenge despite extensive prior treatment exposure
No toxicity grading, objective response rate, or detailed radiographic assessment reported.
This case suggests T-DXd rechallenge may warrant consideration in selected HER2-mutant NSCLC patients after progression and intervening therapy when options are limited, but the finding is from a single patient and should not guide practice without supporting cohort or trial evidence. Clinicians should note the tolerable safety profile in this case (no ILD recurrence) but await prospective data before routine application.
A single case report of T-DXd rechallenge in HER2-mutant lung cancer showing clinical benefit; interesting but cannot establish efficacy or safety generalizable to practice without prospective data.
As stated by the source record.
Quoted from the source exactly as published.
This case suggests T-DXd rechallenge may warrant consideration in selected HER2-mutant NSCLC patients after progression and intervening therapy when options are limited, but the finding is from a single patient and should not guide practice without supporting cohort or trial evidence. Clinicians should note the tolerable safety profile in this case (no ILD recurrence) but await prospective data before routine application.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Introduction Trastuzumab deruxtecan (T-DXd; DS-8201) has emerged as a standard later-line therapy for patients with HER2-mutant non-small cell lung cancer (NSCLC), but the optimal treatment strategy after disease progression using T-DXd remains unclear. Case presentation We report the clinical course of a female lung adenocarcinoma patient with a HER2 exon 20 mutation who achieved long-term disease control with T-DXd despite multiple lines of chemotherapy, until interstitial pneumonia occurred when combined with a PD-1 inhibitor. After a two-month treatment break, the patient fully recovered from interstitial pneumonia using corticosteroid therapy. After recovery, two additional lines of chemotherapy were administered but produced limited benefit. Thus, T-DXd was reintroduced to control the worsening disease. Notably, T-DXd rechallenge, administered systemically along with local embolization, again provided clinical benefit despite prior radiographic progression on T-DXd and intervening systemic therapies. Overall, the patient achieved prolonged disease control during rechallenge (progression-free survival 14 months) without recurrence of interstitial lung disease (ILD) despite the extensive prior treatment exposure. Conclusion This case differs from previously reported rechallenge experiences that mainly describe re-exposure after toxicity-related interruption as the rechallenge reported here followed documented disease progression and multiple intervening regimens, suggesting that, in carefully selected patients with HER2-mutant NSCLC who previously responded to T-DXd, rechallenge after progression could be explored as an option when therapeutic alternatives are limited. However, caution is advised and evidence from prospective and real-world cohorts is needed.
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