Study Estimates Impact of Targeted Treatments in NSCLC

In an effort to estimate the years of life lost (YLL) with current non-small cell lung cancer (NSCLC) treatments based on molecular or biomarker subgroup, researchers evaluated all targeted therapies, chemotherapy, and immuno-oncology (IO) regimens approved by the FDA for these patients through March 3, 2021.

Although the findings suggest targeted therapies have paved the way for progress in survival benefits for young patients with NSCLC and actionable mutations, “it is evident that these therapies still leave a wide gap in the YLL in these younger patients compared to generally older individuals with advanced NSCLC without targetable mutations,” authors wrote.

Previous molecular profiling of adenocarcinoma tissue has revealed the presence of targetable mutations, including epidermal growth factor receptor (EGRF), anaplastic lymphoma kinase (ALK) ROS1, MET, RET, BRAF, and ERBB2/HER2, while additional research suggested driver mutations are associated with diagnosis at a younger age.

In the current analysis, treatment response was defined as median duration of response (DOR) reported in clinical trials. To calculate YLL, 78.7 was used as the median US life expectancy.

“To estimate the YLL for each driver mutation, we calculated the difference in the median age of cancer diagnosis for patients with the respective driver mutation and the average age of cancer diagnosis for patients who do not have a driver mutation,” authors explained.

A total of 19 targeted therapies approved by the FDA or recommended by National Comprehensive Cancer Network guidelines were included in the retrospective cross-sectional study.

Analyses revealed:

• Median ages at diagnosis for patients whose tumors expressed targetable mutations were: 47.6 (NTRK); 52.0 (ALK); 62.0 (HER2); 57.0 (ROS1); 61.4 (RET); 63.0 (BRAF); 69.0 (EGFR); and 72.0 (MET)
• Median age at diagnosis for patients without driver mutations, regardless of PD-L1 status was 71 years
• Median DOR for patients whose tumors expressed the same mutations included: 0.9 (NTRK); 3.9 (ALK); 0.6 (HER2); 6.2 (ROS1); 2.2 (RET); 1.5 (BRAF); 3.1 (EGFR); and 2.4 (MET)
• Median DOR for patients without driver mutations was 1.2 years
• The cumulative estimated survival time for patients whose tumors expressed targetable mutations were: 48.5 (NTRK); 55.9 (ALK); 62.6 (HER2); 63.2 (ROS1); 63.6 (RET); 64.5 (BRAF); 72.1 (EGFR); and 74.4 (MET)
• Cumulative estimated survival time for patients without driver mutations, regardless of PD-L1 status, was 72.2 years of age

Researchers also found NSCLC is diagnosed 8 to 23.4 years earlier in patients with mutations, while the percent difference ameliorated in YLL by mutation type was 44.3 (ROS1), 28.2 (EGFR), 22.9 (RET), 20.5 (ALK), 18.8 (BRAF), 6.4 (HER2), and 3.7 (NTRK) in years.

Although data showed several of these therapies can provide durable responses in patients with NSCLC not seen with traditional chemotherapy, authors cautioned patient demographics need to be taken into account and weighed against these benefits.

“Even under the most optimistic scenario with all targeted therapies employed, many of these younger patients still carry a greater burden of YLL compared to those older patients with NSCLC without targetable mutations,” they explained.

Analyses employed may have overestimated the therapeutic benefit of each targeted therapy, marking a limitation to the study. In addition, investigators could not account for changes in treatment resulting from TKI resistance mechanisms and did not include all potential therapies used off-label for NSCLC with actionable mutations.

“The progress made in targeted therapies for advanced NSCLC is commendable and deserves praise, but it is unmistakable that considerable progress is still to be made before patients can bridge the gap in YLL,” authors concluded.

Reference

Benjamin DJ, Haslam A, Gill J, and Prasad V, et al. Targeted therapy in lung cancer: are we closing the gap in years of life lost? Cancer Med. Published online March 22, 2022. doi:10.1002/cam4.4703