Early Molecular Genotyping Testing Results Confer OS Benefit in Advanced NSCLC

"We found that in a real-world cohort of patients newly diagnosed with treatment-naïve metastatic, nonsquamous NSCLC…the availability of molecular genotyping results before [frontline] therapy was associated with a substantial improvement in OS," according to the study authors.

Patients with metastatic nonsquamous non–small cell lung cancer (NSCLC) and available molecular genotyping results experienced a significant improvement in overall survival (OS) following first-line therapy compared with those with unavailable testing, according to findings from a real-world cohort study published in the Journal of Clinical Oncology Precision Oncology.

With a median follow-up of 14.2 months, the median OS was 24.6 months (95% CI, 18.6-not reached) in patients with available testing vs 6.2 months (95% CI, 2.8-10.3) in those without available testing in an unadjusted analysis (P < .0001). After adjusting for covariates, an OS advantage occurred in the available testing group (HR, 0.43; 95% CI, 0.30-0.62; P <.0001). After adjusting for available ECOG performance statuses within 90 days of diagnosis, investigators continued to observe longer survival among patients with available testing (HR, 0.45; 95% CI, 0.31-0.66; P <.0001).

Across patients with available testing with or without complete testing, those with unavailable plus comprehensive testing, and those with unavailable plus incomplete testing, investigators noted a significant difference in survival outcomes in the 3 groups (P <.001). Compared with those who had available testing, worse survival outcomes occurred among those in the unavailable plus comprehensive testing group (HR, 2.11; 95% CI, 1.43-3.13; P = .0002) and those in the unavailable plus incomplete testing group (HR, 3.43; 95% CI, 1.84-6.40; P = .0001).

“We found that in a real-world cohort of patients newly diagnosed with treatment-naïve metastatic, nonsquamous NSCLC… the availability of molecular genotyping results before [frontline] therapy was associated with a substantial improvement in OS,” the study authors wrote. “This finding remained robust in several secondary and sensitivity analyses, including complete case analyses for [performance status] and sensitivity analyses for unmeasured confounding.”

Investigators of this real-world cohort study assessed patients with metastatic nonsquamous NSCLC at the University of Pennsylvania between January 2019 and December 2020. Tissue genotyping consisted of using an in-house DNA-based next-generation sequencing panel plus a targeted RNA sequencing fusion panel based on standard testing pathways.

The primary end point was OS and how the availability and completeness of molecular genotyping impacted OS. Secondary end points included the relationship between testing modality; concurrent tissue and plasma testing; and test result availability.

Patients who had more than 2 office visits at the University of Pennsylvania’s academic practice, or 2 affiliated community practices, were eligible for inclusion in the study. Of 326 patients, 261 had available molecular genotyping results prior to beginning first-line therapy, and 65 did not have these results available.

Baseline characteristics including demographics, smoking status, and histology were generally consistent between the available and unavailable testing groups. Across the overall study population, the median age was 66.0 years (range, 29.0-93.0), and most were female (54.0%). Additionally, most patients were former smokers (64.4%), had adenocarcinoma histology (70.9%), received treatment at the academic site (77.3%), and underwent tissue and plasma testing (66.3%). Moreover, 45.4% of patients had clinically actionable mutations.

Among 233 patients without a targetable mutation, the median OS was 18.2 months (95% CI, 13.4-24.6) in the available testing group vs 5.4 months (95% CI, 2.8-9.2) in the unavailable testing group (P <.0001). Investigators continued to observe higher OS in the available testing group among patients without targetable mutations after adjusting for covariates (HR, 0.46; 95% CI, 0.32-0.68; P <.0001).

Concurrent testing with tissue and plasma samples correlated with a significantly higher probability of having test results available prior to frontline therapy compared with tissue testing alone after adjusting for covariates (adjusted odds ratio, 2.06; 95% CI, 1.09-3.90; P = .026).

According to the investigators, the results should be interpreted with caution based on the intrinsic limitations of an observational study as opposed to a randomized study. Additionally, the OS may have been lower in the unavailable testing group due to potential factors including the burden of sickness, frailty, a high number of patients with an ECOG performance status of 2, or the need to begin therapy sooner due to rapidly declining clinical status.

Reference

Aggarwal C, Marmarelis ME, Hwang WT, et al. Association between availability of molecular genotyping results and overall survival in patients with advanced nonsquamous non-small-cell lung cancer. JCO Precis Oncol. 2023;7:e2300191. doi:10.1200/PO.23.00191