Called LP-300 , the Lantern drug increased overall survival from 13 months to more than 27 , compared to chemotherapy alone , in female nonsmokers , in a small trial . It “ targets molecular pathways that are more common in female nonsmokers than in any other group ,” said Sharma , targeting the mutations EGFR , ALK , MET , and ROS1 ( common in never-smokers ) directly and boosting the efficacy of other drugs that attack them , such as erlotinib and crizotinib . Lantern plans a larger trial this year .
Smokers ’ tumors tend to have more mutations overall , thanks to mutagen-packed cigarette smoke attacking their lungs , but scientists have developed more drugs for never-smokers ’ lung tumors than for smokers ’. For instance , EGFR and ALK mutations are more common in never-smokers . ( Mandi Pike had the EGFR mutation , which was relatively fortunate : A drug targets it , and she has been cancer-free since November .)
The targeted drugs bollix up each mutation ’ s cancer-causing effects . KRAS mutations are more common in smokers ’ lung tumors , and there are no KRAS drugs . ( A KRAS drug for lung cancer is imminent , though , said thoracic oncologist Ben Creelan of Moffitt Cancer Center in Tampa , Fla .)
According to national guidelines , lung cancer in never-smokers should be treated the same as in smokers , said Creelan . “ But I think we should reconsider this ,” he said .
Because never-smokers have fewer tumor mutations , it ’ s harder to find them . So he said clinicians should be more aggressive about looking for actionable mutations in these patients . “ I keep looking for a mutation until I find something important ,” he said , adding that doctors might need better biopsy material or to use a different sequencing method in never-smokers .
In a cruel twist , the breakthrough drugs that take the brakes off immune cells , which then attack the tumor , are less effective in never-smokers ’ lung cancer than in smokers ’. The reason seems to be that smokers ’ tumors have more mutations , said Mount Sinai ’ s Kaufman ; the mutations often cause the tumor cells to have molecules on their surface that the immune system perceives as foreign and revs up to attack . Never-smokers ’ tumors have few , if any , of those “ come and get me ” molecules . Immune cells therefore ignore them .
“ In smokers , conversely , with more mutations , there is more for the immune system to recognize as bizarre and foreign , and so to provoke ” an attack , Creelan said .
In contrast , never-smokers ’ tumors are more likely to respond to targeted drugs , and as a result to be in remission for a long time or even cured . That ’ s because with fewer mutations , never-smokers ’ tumors are more likely to have an “ oncogene addiction ,” Heymach explained : They are propelled by only one mutation . The plethora of mutations in smokers ’ tumors means that there is usually a back-up cancer driver if a targeted drug eliminates cells with only one . “ When a tumor has more and more mutations , blocking one is less likely to have an impact ,” Heymach said . “ But in nonsmokers , it can .”