Utility of comprehensive genomic profiling in directing treatment and improving patient outcomes in advanced non-small cell lung cancer

Abstract

Background With the identification of new targetable drivers and the recent emergence of novel targeted drugs, using comprehensive genomic profiling in lieu of the routine testing for classic drivers in the clinical care for advanced NSCLC has been increasingly advocated. However, the key assumption justifying this practice, that comprehensive genomic profiling could lead to effective anticancer therapies and improve patient outcomes, remains unproved. Methods Comprehensive genomic profiling was prospectively applied in 1564 advanced NSCLC patients to identify potentially actionable genomic alterations. Patients were assigned to genotype-matched targeted therapies or nonmatched therapies based on the profiling results. Its utility in directing treatments was determined by the proportion of patients receiving genotype-matched targeted therapies and the proportion of patients being enrolled into genotype-matched clinical trials. Its impacts on patient outcomes were assessed by comparing progression-free survival (PFS) and overall survival (OS) between patients who received a genotype-matched and nonmatched therapy. Results From October 2016 to October 2019, tumor genomic profiles were established in 1166 patients, leading to a matched targeted therapy in 37.7% (n = 440) and a genotype-matched trial enrollment in 20.9% of patients (n = 244). Potentially actionable alterations were detected in 781 patients (67.0%). For these patients, a genomic profiling-directed matched therapy significantly improved PFS (9.0 months vs 4.9 months, P < 0.001) and OS (3.9 years vs 2.5 years, P < 0.001) compared with a nonmatched therapy. Excluding patients with standard targeted therapies, genomic profiling led to a matched targeted therapy in 16.7% (n = 24) and a matched trial enrollment in 11.2% (n = 16) of patients. No PFS (4.7 months vs 4.6 months, P = 0.530) or OS (1.9 years vs 2.4 years, P = 0.238) benefit was observed with the use of genotype-matched targeted therapies in this population. Conclusions Comprehensive genomic profiling is of clinical utility in assisting treatment selection, facilitating clinical trial enrollment, and improving patient outcomes in advanced NSCLC. However, for patients carrying alterations without standard-of-care targeted drugs, the interpretation of genomic profiling results should be careful given the low likelihood of benefit from the investigational or off-label use of targeted therapies in this population in the current treatment landscape. Trial registration ChiCTR1900027582 (retrospectively registered on 19 November 2019)

Genomic features and its potential implication in bone oligometastatic NSCLC

“…Here, we detected that 74.19% of bone oligometastatic patients had at least one actionable alteration according to OncoKB evidence. This percentage was slightly higher than the 67% of 1564 patients with usual advanced NSCLC reported in previous study [ 54 ], suggesting genetic alterations in bone oligometastasis are highly targetable. And the proportion of patients with level 1–2 actionable alterations as their highest actionable targets was also higher than the conventional advanced NSCLC patients (64.51% vs 57.1%) [ 54 ].…”

Real-world analysis of different intracranial radiation therapies in non-small cell lung cancer patients with 1–4 brain metastases

“…An MRI radiomics method using clinical and radiomic features could predict the BM response to SRS as well as the treatment outcome, including local tumor control and survival [ 23 ]. Comprehensive genomic profiling is of clinical utility in assisting treatment selection, facilitating clinical trial enrollment, and improving patient outcomes in advanced NSCLC [ 24 ].…”

Patient and Clinician Preferences for Genetic and Genomic Testing in Non-Small Cell Lung Cancer: A Discrete Choice Experiment

“…CGP facilitates the early identification of actionable genomic alterations and appropriate treatment selection while reducing the need for re-biopsy, thus improving outcomes and quality of life in people with NSCLC [ 33 , 34 ]. This is particularly important given the large proportion of patients who are diagnosed with NSCLC at the most advanced stages [ 3 ].…”

“…CGP/WES/WGS/larger NGS panels can also identify co-occurring genetic alterations to better define genomic complexity and prognosis in patients with NSCLC [ 35 ]. This is particularly important for patients who have undergone multiple lines of treatment and have developed multiple resistance mutations as well as providing opportunities to access clinical trials [ 33 ]. Despite this, significant barriers in the uptake of CGP have been reported in the Australian setting [ 36 ] and depend highly on local expertise and resources.…”