Is It Time to Consider Germline Testing for All Lung Cancer Patients?

All patients with lung cancer should be considered for germline genetic testing, according to an ASCO Plenary Series presentation.

Researchers conducted a study of nearly 8000 patients with lung cancer and found that roughly 15% of these patients had pathogenic germline variants (PGVs). About 95% of those PGVs were potentially clinically actionable.

Because germline testing is recommended in patients with other cancers, the researchers concluded that all patients with lung cancer should also be considered for germline testing, said study author and presenter Renato Martins, MD, of the VCU Massey Cancer Center in Richmond, Virginia.

Dr Martins noted that germline testing is not currently recommended by the National Comprehensive Cancer Network (NCCN) for patients with lung cancer. However, the NCCN recommends germline testing for patients with pancreatic, ovarian, colorectal, and breast cancers. 

Dr Martins and colleagues set out to assess the value of germline testing in lung cancer by determining the prevalence of PGVs and any corresponding clinical implications.

The researchers analyzed data from 7788 patients with lung cancer. They underwent germline genetic testing, conducted by commercial laboratories, between 2014 and 2022. The mean age at testing was 63 years, and 71.1% of patients were women. 

A majority of patients (71.1%) had a personal history of other cancers in addition to lung cancer. Most patients (64.5%) were White, and similar percentages of patients were Black (5.4%), Hispanic (5.1%), Asian/Pacific Islander (5.0%), and multiracial (5.2%). The remaining patients were classified as “other” (10.3%) or unknown (4.5%) race/ethnicity. 

The median number of genes tested was 79. In the entire cohort, 49.3% of patients were negative for a PGV, and 32.8% had a variant of undetermined significance (VUS). 

A PGV or likely PGV was identified in 14.9% of patients. The remaining 2.9% of patients were “carriers,” which meant they were heterozygous for an autosomal recessive cancer predisposition syndrome. 

The vast majority of PGVs (95.1%) were deemed clinically actionable. PGVs were considered clinically actionable if they were used in clinical trial eligibility criteria or if they were associated with recommendations from NCCN or other professional societies.

More than half of PGVs (61.3%) were present in a DNA damage repair (DDR) or homologous recombinant (HRR) gene. Germline mutations were most commonly detected in BRCA2 (2.8%), followed by CHEK2 (2.1%), ATM (1.9%), TP53 (1.3%), BRCA1 (1.2%), EGFR (1.0%), APC (0.9%), and PALB2 (0.5%).

When the cohort was restricted to patients who had lung cancer only (no prior cancer history), 16.0% of patients were positive for PGVs, 3.4% were carriers, 33.6% had VUS, and 47.0% were negative for PGVs. Germline mutations were most commonly seen in BRCA2 (3.4%), EGFR (2.1%), ATM (2.0%), CHEK2 (1.9%), TP53 (1.3%), BRCA1 (1.2%), APC (1.0%), PALB2 (0.9%), BAP1 (0.7%), MSH6 (0.5%), and PMS2 (0.5%).

Dr Martins acknowledged that a potential limitation of this study was that “the referral for genetic testing may reflect a selection bias due to personal medical history or family history of cancer, making this cohort not representative of all patients with lung cancer in the general population.”

Nevertheless, Dr Martins said these results support the use of germline testing in patients with lung cancer.

“Given the current NCCN recommendations for germline testing in patients diagnosed with other cancer types, the Moonshot version 2.0 recommendations, and the profound implications for both patients and their families that results from identifying a PGV, our results suggest that all patients diagnosed with lung cancer should be considered for germline testing,” Dr Martins said. 

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Sorscher S, LoPiccolo J, Chen E, et al. Landscape of pathogenic germline variants in patients with lung cancer. Presented at ASCO Plenary Series; August 16, 2022. Abstract 388570.

This article originally appeared on Cancer Therapy Advisor