Table 3.
Ongoing prospective biomarker studies in early-stage non-small cell lung cancer.
| Trial | Stage/histology | Treatment arms | Study design (LOE) | Biomarker(s) (assay type) |
|---|---|---|---|---|
| SWOG-S0720 | I (pT ≥ 2 cm) [AJCC 6th ed] | Cisplatin/gemcitabine (↓RRM1 and/or ERCC1) versus observation (↑ RRM1 and ERCC1) | Phase II (feasibility) (I) | ERCC1, RRM1 (AQUA ± RT-qPCR ± protein polymorphisms) |
| ITACA | II–III [AJCC 6th ed] | Pharmacogenomic-guided ChT regimen versus control* | Phase III (I) | ERCC1, TS (RT-qPCR) |
| TASTE | II–IIIA (pN1) [AJCC 6th ed] /Non-SCC lung cancer | Customized treatment versus cisplatin/pemetrexed$ | Randomized phase II (feasibility)-3 (I) | ERCC1 (IHC), EGFR (mutations) |
| GECP-SCAT | pN1-N2 [AJCC 6th ed] | Customized ChT versus cisplatin/docetaxel‡ ± RT (pN2) | Phase III (I) | BRCA1 (RT-qPCR)/EGFR, KRAS (mutations) |
| RADIANT | IB-IIIA [AJCC 6th ed] | Erlotinib versus placebo ± adjuvant ChT (up to 4 cycles) | Phase III (I) | EGFR (IHC ± FISH)/EGFR, KRAS (mutations)§ |
AJCC, American Joint Committee on Cancer; AQUA, automated quantitative analysis; BRCA1, breast cancer susceptibility gene 1; ChT, chemotherapy; EGFR, epidermal growth factor receptor; ERCC1, endonuclease excision repair cross-complementing 1; FISH, fluorescent in situ hybridization; GECP-SCAT, Spanish Lung Cancer Group (Grupo Español de Cáncer de Pulmón)-Spanish Customized Adjuvant Trial; IHC, immunohistochemistry; ITACA, International Tailored Chemotherapy Adjuvant; KRAS, kirsten rat sarcoma viral oncogene homolog; LOE, level of evidence for grading clinical utility of tumor markers [Hayes et al. 1996]; Non-SCC, non-squamous-cell; RADIANT, Randomized Double-blind Trial in Adjuvant NSCLC with Tarceva; RRM1, ribonucleotide reductase M1; RT, radiotherapy; RT-qPCR, real-time quantitative polymerase-chain reaction; SCAT, Study of Customized Adjuvant Chemotherapy; SWOG, Southwest Oncology Group; TASTE, Tailored Post-Surgical Therapy in Early Stage NSCLC; TS, thymidylate synthase.
Individualized chemotherapy according to the pharmacogenomic profile: taxane (↑ERRC1 and TS mRNA levels), or pemetrexed (↑ERRC1, ↓TS mRNA levels), or cisplatin/gemcitabine (↓ERRC1, ↑TS mRNA levels), or cisplatin/pemetrexed (↓ERRC1 and TS mRNA levels) versus standard chemotherapy with a platinum-based doublet chosen by the investigator.
$Customized treatment according to EGFR and ERCC1 status: erlotinib (EGFR-mutant tumors) or observation (EFGR-wild type and ERCC1-positive tumors) or cisplatin/pemetrexed (EGFR-wild type and ERCC1-negative tumors).
Customized chemotherapy: docetaxel (high BRCA1 levels) or cisplatin/docetaxel (intermediate BRCA1 levels) or cisplatin/gemcitabine (low BRCA1 levels).
Secondary exploratory analysis.