Traveling Through the Lung Cancer Treatment Paradigm: Taking TKI-Related AEs Into Consideration for NSCLC

In this sixth episode of OncChats: Traveling Through the Lung Cancer Treatment Paradigm, Aaron Franke, MD, discusses the consideration of adverse effects related to treatment with TKIs patients in non–small cell lung cancer.

"[There is something else that] has become very clinically important. I know most clinicians in the field—even those in private practice who are treating 25 different types of tumors in a day—have probably heard the mantra of ‘Wait for the next-generation sequencing [NGS] [results] before treating [patients with] advanced metastatic non–small cell lung cancer.’ However, I think this is a good reminder.

We still see cases [of] heavy smokers, [those] 78 years [of age], veteran patients who you have no ‘suspicion’ of having a driver mutation; their PD-L1 [testing] comes back at 90%, [and] they’re symptomatic so you want to give chemotherapy [and] immunotherapy. You give a reasonable regimen, and then, despite the smoker [status,] despite the age, despite the lack of being the general phenotype, the NGS [results] come back, and he or she has an ALK [mutation], an EGFR [mutation], a ROS1 [fusion], ora RET or MET [alteration].

The problem is now you have an immune checkpoint inhibitor floating around for realistically, weeks to months. You’re kind of slated to deal with that fact in that you want to start a targeted therapy, which most would recommend at this point, but you’re thinking about the synergistic toxicities with these therapies...There is also the bigger unknown space of the ROS1 and the RET drugs, where we don’t know as much about what kind of toxicities lie ahead for patients who have immune checkpoint inhibitors floating around. However, I think we have learned the story from EGFR inhibitors.

I’ve had more than a couple of patients who have been in this scenario. Especially for patients who maybe already have compromised lung function, I will sometimes start them on an older-generation TKI and try to wait out that window before starting, let’s say,osimertinib [Tagrisso,] which again gives you a higher-than-acceptable rate of pneumonitis in the setting of recent checkpoint inhibitors. A patient [who already has] chronic obstructive pulmonary disease—again, they are the smoker, or they are the [patient with the] unexpected EGFR [mutation]—may have very little wiggle room in terms of a window or a margin of error to have a pneumonitis toxicity. In [this] case, they may not be candidates [to receive] any more systemic therapy, despite how efficacious and tolerable it may be. You may not only lose the window, but you may also have blown the gap there.

As such, I think these are very important considerations. Don’t be fooled by the PD-L1 [status]. Always wait on the NGS [testing results]—even for the smokers and the older patients; [they still] make up maybe 15% or up to 20% of [all] oncogene-driven lung cancers, so that’s not an insignificant number."