TORONTO, November 8, 2021 – Adjuvant treatment with gefitinib, a good alternative to current standard-of-care cisplatin-based chemotherapy for patients with epidermal growth factor receptor (EGFR)–mutant stage II-III non-small-cell lung cancer (NSCLC), prolongs time to relapse and improves the quality of life. However, not all patients experienced favorable clinical outcomes with tyrosine kinase inhibitor treatment, raising the necessity for further biomarker assessment. Today, Geneseeq and Guangdong Provincial People’s Hospital published results from the ADJUVANT CTONG1104 trial in Nature Communications, that applied GeneseeqPrimeTM Panel, to identify predictive molecular biomarkers and establish a multi-gene MINERVA scoring system for adjuvant therapy, guiding personalized adjuvant treatment decisions.

The ADJUVANT-CTONG1104 trial, the first phase III exploratory biomarker study on the adjuvant therapy in EGFR-mutated lung cancer population, examined the survival benefit of adjuvant gefitinib against adjuvant chemotherapy (vinorelbine and cisplatin, VP) in patients with stage II-IIIA EGFR-mutant NSCLC. The exploratory cohort enrolled 171 resected NSCLC patients with EGFR 19 deletion or EGFR L858R, including 95 adjuvant gefitinib-treated patients and 76 adjuvant VP-treated patients. The adjuvant gefitinib-treated group showed a superior disease-free survival compared with the VP group (31.7months vs 19.6months)1. Genome profiling of tumor tissues allowed researchers to identify five predictive biomarkers for adjuvant treatment, including TP53 exon4/5 mutations, RB1 alterations, and copy number gains of NKX2-1, CDK4, and MYC. Given the high tumor heterogeneity of lung cancer, these predictive biomarkers were further integrated as the Multiple-gene INdex to Evaluate the Relative benefit of Various Adjuvant therapies (MINERVA) score, a predictive score based on Z scores of each biomarker, and combination of variables method. The MINERVA score categorized patients into three subgroups with distinct survival outcomes including highly TKI-Preferable group(HTP, significant superiority with adjuvant gefitinib), TKI-Preferable group(TP), and Chemo-Preferable Group(CP). The MINERVA multi-gene score was internally validated using ten-fold cross-validation and leave-one-out cross-validation procedures, and then externally validated in an independent cohort from the EMERGING-CTONG1103 trial.

“Comprehensive evaluation of the patient’s baseline molecular profile is crucial for optimal personalized treatment strategy for cancers at all stages,” said Dr. Hua Bao, author and R&D Director of Geneseeq. In recent years, clinical trials such as ADAURA and EVAN have highlighted the importance of targeted therapy as adjuvant treatment for early NSCLC, therefore early and mid-stage tumor perioperative management is no longer limited to radical treatment. Next-generation sequencing has been employed to reveal the characteristics of baseline genomic landscape and postoperative minimal/molecular residual disease to predict the risk of recurrence and metastasis of patients.

Reference

  1. Zhong, W.-Z. et al. Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II–IIIA (N1–N2) EGFR-mutant NSCLC (ADJUVANT/CTONG1104): a randomised, open-label, phase 3 study. The Lancet Oncology 19, 139–148 (2018).

 

Lung Cancer Nature Communications NGS