Treatment Choices for EGFR+ NSCLC

Martin Dietrich, MD, PhD:We have 5 EGFR TKIs [tyrosine kinase inhibitors] approved. Osimertinib has crystallized out to be the treatment option of choice due to its overall survival benefit as shown in the FLAURA trial, as well as its favorable toxicity profile. It is the preferred guideline choice and probably the most commonly used EGFR TKI in the first-line setting, if it is available.

The FLAURA trial was a randomized phase III trial comparing osimertinib against erlotinib or gefitinib, which were basically the standard of care EGFR TKIs in the United States and in Asia, respectively. And progression-free survival was reported 2 years ago, and we received overall survival data at the ESMO [European Society for Medical Oncology Congress 2019] meeting, demonstrating an overall survival of roughly 38 months as opposed to a comparator arm that ended at around 32 months, so roughly a 6-month survival benefit. These are data that have to be interpreted in the context of the crossover option for second-line patients.

Roughly 50% of patients develop an EGFR resistance with a T790M mutation, for which osimertinib has a second-line indication. And I think that hampered a little bit the impressiveness of the overall survival benefit. We did see a gentler toxicity profile with osimertinib. The most common adverse effects are really on-target effects due to EGFR distribution in the epidermis, with rash and diarrhea. But they were infrequent, and they were typically very easily manageable. We understand very well how they occur and how to treat them, so it’s typically a regimen that is very well tolerated.

PD-L1 [programmed death-ligand 1] in theEGFR-mutated space has no data to support use yet. We’ve seen some interesting data from the IMpower150 study, where theEGFRpatient population seemed to be doing quite well with the quadruplet of chemotherapy, an antiangiogenic inhibitor with Avastin [bevacizumab], and immunotherapy with a PD-L1 inhibitor. These are obviously subset data that may not yet be practice-changing, so my current recommendation is to avoid immunotherapy outside the setting of a clinical trial. And if there’s no clinical trial available, I think the best piece of data, even though it’s a weak piece of data, would be the IMpower150 regimen with a quadruplet of an antiangiogenic inhibitor, chemotherapy, and immunotherapy. It is certainly not to be used prior to exploiting the complete sequence of EGFR targeting agents, including the ablation of isolated lesions and trying to extend the time on an EGFR TKI for as long as possible.

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