Treatment Patterns and Survival of Patients With Advanced Non-Small Cell Lung Cancer Guided by Comprehensive Genomic Profiling: Real-World Single-Institute Study in China

Abstract

Although the National Comprehensive Cancer Network and the Chinese Society of Clinical Oncology guidelines recommend comprehensive genomic profiling of lung adenocarcinoma, it has not been widely applied in Chinese hospitals. This observational study aimed to determine real-world evidence of whether comprehensive genomic profiling can benefit the survival of patients with lung cancer. We investigated the frequency of genomic alterations, treatment strategies, and clinical outcomes in 233 patients with advanced non-small cell lung carcinoma who were routinely screened using a 508-gene panel. The most prevalent drivers were mutations of EGFR (51%), KRAS (9%), PIK3CA (7%), ALK (7%), MET (6%), and BRAF (5%). Mutations in tumor suppressor genes included TP53, KEAP1, RB1, PTEN, and APC. Median overall survival (OS) was significantly shorter among patients harboring KRAS (mutant, n = 17; WT, n = 154) and TP53 (mutant, n = 103; WT n =68) mutations (11.3 vs. 24.0 months; P = 0.16 and 18.7 vs. 28.7 months; P = 0.018, respectively). The OS was longer among patients with tumors harboring EGFR (P = 0.069) and ALK (P = 0.51) mutations. Most patients (65.4%) with the driver gene-positive (EGFR, ALK, and ROS1) tumors were received TKI treatment, whereas those with driver gene wild tumors (53.1%) chose platinum-based therapy. Univariate and multivariate analyses associated a shorter OS among patients with tumors harboring concomitant TP53 and EGFR mutations. These findings provide additional evidence from real-world on the potential importance of targeted therapies as a treatment option in NSCLC patients harboring clinically actionable mutation.

Identifying Actionable Variants Using Capture-Based Targeted Sequencing in 563 Patients With Non-Small Cell Lung Carcinoma

“…We identified 556 variants, with 416 potentially actionable variants in 54.88% (309/563) patients. The percentage of patients harboring actionable genetic alterations is slightly lower than the previous studies (62%) (31). This is due to the small target gene panel.…”

Epidermal growth factor receptor compound and concomitant mutations: advances in precision treatment strategies

“…Similar inferior survival benefits were also found in several studies for specific concomitant EGFR mutations, including MET amplification, PTEN deletion, TP5 3 mutation, and PIK3CA mutations [55–59] . However, Labbé et al [60] found no significant survival difference associated with TP53 status in EGFR -mutant patients administered both first- and third-generation EGFR-TKIs, except patients with concomitant TP53 missense mutations (PFS: HR = 1.91, 95% CI: 1.01–3.60, P = 0.04).…”

“…[53] Besides, Jiang et al [54] Similar inferior survival benefits were also found in several studies for specific concomitant EGFR mutations, including MET amplification, PTEN deletion, TP53 mutation, and PIK3CA mutations. [55][56][57][58][59] However, Labbé et al [60] found no significant survival difference associated with TP53 status in EGFR-mutant patients administered both firstand third-generation EGFR-TKIs, except patients with concomitant TP53 missense mutations (PFS: HR = 1.91, 95% CI: 1.01-3.60, P = 0.04). A phase Ib/II study also showed that patients with advanced EGFR mutations with concomitant TP53 mutations had PFS comparable to that of patients with wild-type TP53 (14.0 months vs. 15.4 months, P = 0.32) who received the novel second-generation EGFR-TKI mefatinib.…”

Aumolertinib challenge as an optional treatment in advanced non small‑cell lung cancer after osimertinib failure with epidermal growth factor receptor‑sensitive mutation: A case series

“…In 2020, the Chinese Society of Clinical Oncology (CSCO) guidelines approved aumolertinib as a second-line treatment for patients with advanced NSCLC and T790M mutation. In 2021, CSCO guidelines recommended aumolertinib as a first-line treatment for patients with advanced NSCLC and EGFR-sensitive mutations ( 7 ). Recently, some reports have emerged on the alternatives for overcoming resistance to osimertinib, such as use of brigatinib alone or in combination with cetuximab ( 8 , 9 ).…”