Waiting for Results of Molecular Testing in NSCLC

Martin Dietrich, MD, PhD:I think molecular testing is crucial for these patients. For adenocarcinomas of the lung in particular, but for all subtypes of non—small cell lung cancer, molecular testing is critical and supported by the guidelines. Without molecular testing, appropriate treatment of non–small cell lung cancer is really not possible. The subtype ofEGFRtreatment is one that we understand quite well and has been the first targeted therapy option for non—small cell lung cancer, with the early introduction of first-generation EGFR TKIs [tyrosine kinase inhibitors]. Obviously the patient was treated along the lines of an EGFR-targeted therapy. It’s important to note for this subtype, immunotherapy is typically not effective, and therefore targeted therapy is the therapy of choice for these patients.

I’d recommend testing for molecular alterations in every patient with lung adenocarcinoma, but you could consider this for other histologies in non—small cell lung cancer as well. Typically, a patient who has an actionable mutation has a several-years-long honeymoon phase that is chemotherapy free. It’s important to note that for most of these molecular alterations, immunotherapy is not effective. And the identification of the molecular alteration is critical because we essentially, if these molecular alterations are missed, are still working in the range of chemotherapy with a significantly shorter overall survival.

Patients who have a diagnosis of lung cancer are eager to get started on therapy. This is a very common clinical discussion. I try to explain to them that their diagnosis is not complete by the introduction of the histological part of their diagnosis, but that their treatment is much more guided by their molecular markers. Those are required, and there’s no urgency in the sense that an additional week or two for testing makes a big impact. Obviously, it’s an additional stressor for patients, but the potential gains are so high that most patients are quite receptive to the idea of awaiting their molecular testing results before jumping on a nonspecific therapy—oftentimes containing chemotherapy—and are willing to undergo testing, oftentimes including a repeat biopsy, to obtain sufficient tissue for an appropriate selection of therapy for the individual genetic subtypes of lung cancer.

I typically counsel my patients about the benefits of targeted therapy, which typically allows for the introduction of the discussion about survival. I try to explain to them that oftentimes years are added on if molecular alterations are found and that lung cancer is no longer the grim diagnosis that it used to be. There’s been significant progress made in the understanding of the biology of the disease that has now translated into a plethora of treatment options that are available already, and there are many to come in the very near future. I’m quite optimistic about identifying these subtypes and try to relay this to patients. I think this is incredibly important.

Starting therapy in the absence of molecular markers is a tremendously difficult clinical scenario. Those are typically highly symptomatic patients, and this should constitute the minority of patients. But if acute treatment is needed, I try to resort to radiation treatment for the management of local symptoms. And if systemic therapy is truly required, I typically choose a combination of chemotherapy alone, typically a platinum doublet of carboplatin and nab-paclitaxel due to its high response rate. In these patients, I do avoid the introduction of immunotherapy. I want to make sure that the targeted therapy options are excluded at the time of adding immunotherapy. And the reason is basically a question of lack of efficacy, but also significant increase of toxicity that seems to be manifesting in the lung with the introduction of TKIs following immunotherapy.

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