How Pharmacists Can Better Manage Patients With NSCLC

In a session at Great Debates & Updates Oncology Pharmacy, Val Adams PharmD, FCCP, FHOPA, BCOP, associate professor, Markey Cancer Center, University of Kentucky, breaks down molecular testing recommendations for non-small cell lung cancer (NSCLC) as well as current challenges facing this disease categorization, and provides pharmacist-guided strategies for overcoming secondary treatment resistant for patients with NSCLC.  

According to Dr Adams, histologic subtypes of NSCLC include adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. He explained that adenocarcinoma is not only the most common subtype, but also common to be in “never-smokers,” and most common to have an actionable mutation. Further, patients who are smokers are most commonly linked with squamous cell carcinoma, and large cell carcinoma is uncommon.  

After highlighting the histologic subtypes, Dr Adams explained the various molecular driver mutations. In adenocarcinoma, the most common mutation is KRAS (25%) with no approved drugs to treat it. Next is EGFR (roughly 15%) with several approved drugs, and ALK (roughly 4-7%) with several approved drugs, as well. Finally, there are a variety of other mutations including, ROS, BRAF, RET, MET (roughly 1-2% each), and all have approved drugs for treatment.  

He also explained that the molecular driver mutations in squamous cell carcinoma are much less likely to harbor an actionable mutation.  

Next, Dr Adams explained the factors involved in testing decision-making for this patient population. He explained that the likelihood of positive findings, positive finding impact of both clinical courses and outcomes, and the overall cost of testing all link together.  

Although there are many tests for targeting mutations, he identified various sampling challenges, too. Sampling challenges he identified included the following:  

• Lung cancer biopsies are less cellular than other solid tumors;
• Bone biopsies yield poor sample due to decalcification, which degrades DNA;
• Quality assurance of genomic medicine;
• Timing of DNA sequencing can take weeks—centralized vs send out to distant laboratory; and
• Quality or quantity not sufficient—needs 10-20% of viable cancer cells in sample for reliable results.

Additional testing includes “reflex testing.” This process examines samples of NSCLC tissue that are identified as non-squamous histology. This testing option is used due to its quick results, however, a con of the test is the cost and ability to handle the volume of patients.  

Dr Adams then asked, “Why do we test?” and he said, “we know from many studies that patients who get chemotherapy as opposed to the targeted therapy specific to their driver mutation do much worse.”  

In the final portion of this session, Dr Adams reviews the impact on drug selection.  

He explained that matching a targeting therapy with a mutational fining is “KEY.” He said, “second, third, or even fourth-generation therapies generally appear more effective than first-generation and commonly improve CNS penetration.”  

“Combination therapy with synergistic drugs that target resistance have shown success,” he continued.  

Additionally, he added, that targeted therapies frequently have slightly different toxicity profiles. He stressed that choosing one that best fits a particular patient always needs to be considered. 

“Retest upon progression to re-evaluate new and different targeted mutations,” Dr Adams concluded.