Targeted Therapy Treatment

Most never-smokers’ lung tumors have targetable mutations matched to FDA-approved drugs, unlike smokers’ tumors. Testing is critical.

Despite the strong link between smoking and lung cancer, a significant number of lung cancer patients have never smoked. A new study analyzed the tumors of 160 never-smokers and found that 78-92% had driver mutations that can be targeted by precision drugs already approved by the FDA. Unlike lung tumors in smokers, most never-smokers’ tumors had these targetable mutations. The study also found differences in never-smokers – 60% were female, few had inherited cancer mutations, and their tumors had less immune activity, explaining their poor response to immunotherapy. The researchers concluded that never-smokers need quality biopsies to identify targetable mutations matched to FDA-approved drugs, as this offers the best chance to effectively treat these mysterious tumors.

While 10-15% of US lung cancers occur in never-smokers (up to 40% in Asia), their causes remain unclear. This study verified never-smoker status through mutation patterns, as smokers’ tumors have 10X more mutations. Only 7% had inherited cancer mutations. Researchers also noted oddities – never-smoker lung cancer is more common in women, unlike most cancers. The tumor immune environments also differ. As we still don’t understand what drives these tumors, the focus is identifying targetable mutations.

The key implication is that quality biopsies and genomic testing are critical for never-smokers to match tumor mutations to precision drugs. As the study found, 80-90% of these mysterious tumors harbor targetable driver mutations, compared to only 50% of smokers’ tumors. While immunotherapy generally doesn’t work for these patients, the high proportion of actionable mutations means FDA-approved targeted drugs offer a key chance to effectively treat never-smoker lung cancer.