Future Directions in Treating NSCLC

Martin Dietrich, MD, PhD:Obviously, non—small cell lung cancer has undergone dramatic changes over the last decade-and-a-half since the introduction of targeted therapy. We have a much better understanding of the different biologies. We have a plethora of targeted agents that are available now with an ever-growing arsenal. We do have to pause for a second and look at the lack of efficacy of immunotherapy in the vast majority of patients. There’s a great deal of hype still surrounding immunotherapy, but it’s only a small subset of patients—roughly one-fourth—that is actually benefitting long term. That’s obviously a significant unmet need. Obviously, additional chemotherapy with immunotherapy combinations will be introduced, hopefully later this year.

I think this is going to be a significant opportunity to close that gap between where we’re at and where we want to be. For those patients who do not have molecular alterations, we will be seeing the introduction of MET inhibitors this year, as well as KRAS inhibitors hopefully. And then the question becomes, should we follow a similar concept like we do with chemoimmunotherapy, where we use some of these targeted agents in combination with immunotherapy to not only achieve a targeted response but also a more durable response by the addition of immunotherapy?

There’s still plenty of work to be done. The majority of patients with lung cancer still don’t do well, even though they do significantly better. I think my biggest hope for the near future is that we approximate where we’re at in terms of knowledge with what we’re doing in practice. I think there’s still a significant gap, especially in the testing realm. I think we have to start thinking about our tissue optimization, but in all honesty, after these many years of trying to obtain proper tissue testing in non—small cell lung cancer, the introduction of liquid biopsy as a close or even concurrent interventional modality is due.

We have 2 prospective datasets that were reported last year, and both showed that—I’m not advocating that tissue biopsy is inferior—in a real-world setting, liquid biopsy carries tremendous value and should be considered virtually as a side-by-side option to the tissue therapy testing to really match what we know about non—small cell lung cancer and what we’re doing for patients in the clinic.

Transcript edited for clarity.

Case: A 60-Year-Old Male with Untreated Stage IVEGFR+NSCLC

Initial presentation

• A 60-year—old Caucasian man presented with shortness of breath, mild dry cough
• PMH: hyperlipidemia, hypertension, medically controlled
• SH: non-smoker, worked 40 years in ship-building industry
• PE: Lungs clear on auscultation bilaterally; anxious-appearing; acknowledges feeling nervous about his health

Clinical workup

• Imaging:
  • Chest x-ray showed a right bronchial lung mass
  • Chest/abdomen/pelvic CT scan revealed a 4.6-cm mass on the right main bronchus and ipsilateral subcarinal lymphadenopathy; positive for a single suspicious 2-cm hepatic lesion on the right lobe
  • PET scan showed activity in the right main bronchus and subcarinal nodal area, hepatic lesion was shown to be avid
  • Brain MRI negative for metastases
• Patient underwent bronchoscopy with TBNA
• Diagnosis and staging: Biopsy showed high-grade lung adenocarcinoma; T2N2M1b — IVA
• Molecular testing:EGFRexon 21 L858R, PD-L1 TPS 50%
• ECOG PS 0

Treatment

• Patient started on osimertinib 80 mg PO qDay
  • At 3-week follow-up the patient had been tolerating treatment well; continued osimertinib
• Repeated chest/abdomen/pelvic CT with contrast after every 2 cycles,
  • Partial response after 4 cycles, no disease progression at 3, 6 and 12 months
• Imaging at 19-month follow-up revealed a new solitary liver lesion