DDR2 activating mutations are identified in ~2–4% of squamous cell carcinoma of the lung...
Детермінований перегляд YAML-сутності з джерельної бази. Клінічний авторитет лишається за вказаними source ID та статусом клінічного sign-off.
| ID | BMA-DDR2-NSCLC-SQUAMOUS |
|---|---|
| Тип | Клінічна застосовність |
| Статус | переглянуто 2026-05-04 | очікує клінічного підпису | потрібне рев’ю клінічної застосовності |
| Хвороби | DIS-NSCLC |
| Джерела | SRC-ESMO-NSCLC-METASTATIC-2024 SRC-NCCN-NSCLC-2025 |
Дані про клінічну застосовність
| Біомаркер | BIO-DDR2 |
|---|---|
| Варіант | DDR2 activating mutation in squamous cell NSCLC (~2–4%); investigational RTK target; dasatinib inhibits DDR2 but no approved DDR2-selected therapy |
| Хвороба | DIS-NSCLC |
| Рівень ESCAT | IIIB |
| Рекомендовані комбінації | Pembrolizumab 200 mg q3w + carboplatin AUC6 + paclitaxel 200 mg/m² (or nab-paclitaxel 100 mg/m² days 1,8,15) — 1L squamous NSCLC regardless of DDR2 status (KEYNOTE-407; Category 1), Docetaxel ± ramucirumab — 2L squamous NSCLC after platinum failure; DDR2 status does not select therapy |
| Підсумок доказів | DDR2 activating mutations are identified in ~2–4% of squamous cell carcinoma of the lung (enriched in squamous vs. adenocarcinoma). DDR2 signals via SRC and MAPK pathways; dasatinib (a BCR-ABL/SRC/KIT inhibitor) also inhibits DDR2 kinase. Clinical evidence: (1) Preclinical: DDR2 S768R-mutant lines sensitive to dasatinib in vitro; erlotinib not active. (2) Clinical (LUNG-MAP S1400D, NCT02154490): phase II umbrella trial with dasatinib for DDR2-mutant squamous NSCLC was closed early due to insufficient enrollment and limited signals; no significant ORR reported. (3) Case reports: isolated responses to dasatinib in DDR2-mutant squamous NSCLC (Hammerman et al. Cancer Discov 2011); no prospective validation. Standard of care for squamous NSCLC (regardless of DDR2 status): pembrolizumab ± carboplatin/ nab-paclitaxel/paclitaxel (KEYNOTE-789/407) per PD-L1 and histology. DDR2 mutation does not modify treatment algorithm in current guidelines. ESCAT IIIB: prognostic/investigational marker with insufficient clinical evidence to guide therapy selection. |
Нотатки
ESCAT IIIB: DDR2 mutation in squamous NSCLC is an investigational target with no approved therapy. Clinically important distinctions: (1) DDR2 is not in standard NCCN-required biomarker testing (EGFR, ALK, ROS1, BRAF, KRAS, MET, RET, NTRK, PD-L1, TMB); NGS panels may detect it incidentally. (2) SRC inhibitors (dasatinib) have dose-limiting toxicity (fluid retention, pleural effusion) at doses needed for DDR2 inhibition in solid tumors. (3) For DDR2-mutant patients who have progressed on standard therapy, enrollment in a DDR2-targeting basket trial is the recommended approach. (4) DDR2 mutation in CRC or breast cancer has no established clinical significance.
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