Abstract 403P
Background
Squamous cell carcinoma (SqCC) of lung, is known to present in non-smokers in the Asia Pacific region. Disparity remains in the adoption of molecular testing for SqCC lung compared to adenocarcinoma, despite guidelines advocating broad molecular proiling. This study seeks to evaluate the incidence of actionable mutations in lung cancer, with a particular emphasis on SqCC.
Methods
We analyzed 3,326 NGS-based multigene profiling tests from 2,743 lung cancer patients at Datar Cancer Genetics, using tumor tissue DNA (ttDNA, n=1,395) or circulating cell-free DNA (cfDNA, n=1,931), to identify actionable mutations in key driver genes linked to treatment response and resistance.
Results
The most common subtype for molecular testing was adenocarcinoma (86%), followed by squamous cell carcinoma (9%), neuroendocrine tumors (3%), and adenosquamous carcinoma (2%), highlighting less adoption of molecular testing in squamous lung cancer. In cfDNA profiling of SqCC, EGFR mutations were the most common actionable alteration (9.6%), followed by KRAS mutations (4.0%) and MET amplification (0.9%). Interestingly, BRAF mutations were absent in tissue but present in 7.2% of liquid samples. HER2 alterations and ROS1 fusions were absent in both, highlighting their rarity and the intricate molecular landscape of SqCC lung.
Table 403PIncidence of targetable alterations in tissue samples
| Alterations Identified | Lung Cancer (All subtypes) | Adenocarcinoma | Squamous cell carcinoma |
| EGFR | 34.8% | 38.9% | 12.8% |
| KRAS | 15.9% | 18.0% | 5.5% |
| ALK | 8.0% | 8.9% | 3.1% |
| MET amplification | 1.3% | 1.3% | 1.9% |
| MET Exon 14 skipping | 3.6% | 1.3% | 1.8% |
| RET | 1.7% | 2.0% | 1.0% |
| BRAF | 2.9% | 2.8% | 0% |
| ROS1 | 3.1% | 4.0% | 0% |
| HER2 mutations | 2.3% | 2.9% | 0% |
| HER2 amplification | 0.8% | 0.8% | 0% |
| TMB ≥10 muts/mb | 33.5% | 28.7% | 57% |
| PD-L1 TPS ≥1% | 46.1% | 44.1% | 58.3% |
| MSI-High | 0.5% | 0.5% | 0% |
Conclusions
Driver mutations are underrecognized in SqCC-lung. Significant number of SqCC-lung patients are non-smokers in the Asia Pacific region. It would be important to understand what percentage of SqCC-lung cases are driver mutation positive, and utilize this information to help inform and build novel clinical trial strategies in this patient population. With actionable drivers in more than one-fifth cases, SqCC-lung stands out as a tumor type rich in opportunities for targeted therapy. It’s time to recognize SqCC-lung for its unique actionability beyond the adenocarcinoma comparison.
Legal entity responsible for the study
Datar Cancer Genetics
Funding
Has not received any funding.
Disclosure
S. Limaye, A.K. Vaid: Financial Interests, Personal, Advisory Board: Datar cancer genetics. N. Shah, S. Schuster, V. Datta, D. Akolkar, P. Kumar, N. Shrivastava, S. Apurwa, A. Saha: Financial Interests, Personal, Full or part-time Employment: Datar cancer genetics R. Datar: Financial Interests, Personal, Ownership Interest: Datar cancer genetics. All other authors have declared no conflicts of interest.