EGFR+ mNSCLC: Monitoring Treatment Response and Next Steps
Edgardo Santos Castillero, MD, FACP:In this particular case, the medical oncologist decided to treat the patient with erlotinib and ramucirumab based on the profile of this patient, which was exactly the profile of participants in the RELAY study. The patient obtained a partial remission, which is good. Partial remission is defined as more than 30% of response from the baseline, in terms of reduction of tumor size. So you can have 30%, 40%, 50%, even 70%, 80%, 90% reduction, and it still is partial remission. We talk about complete remission only when the tumor completely disappears.
Partial remission has a broad spectrum of response rate. Good partial remission is great for this patient. It will control disease very quickly. But at the end of the day, while we are looking right now in lung cancer in the first line, it is overall survival. In particular, for that RELAY study, as I mentioned before, overall survival is immature, so we cannot make any comment on that. But certainly, a PFS [progression-free survival] of 19.4 months for theEGFR[epidermal growth factor receptor] exon 21 mutation is very provocative, very striking, and it is something that we should have in mind and consider.
On patients who have anEGFRmutation or any other driver mutation, at the time of progression I recommend to rebiopsy the patient. Nowadays, we also have the option of trying a liquid biopsy, which basically is a blood test analysis that tries to identify cell-free DNA from the circulating tumor. We can do these molecular analyses, such as next-generation sequencing, in the blood. If that is negative, it doesn’t mean that the patient doesn’t have another mutation explaining the resistance to the agent we are giving. In those cases, I order a rebiopsy of a visible lesion that will not put the patient in any kind of jeopardya lesion that is close to the chest wall or a lesion in the liver, or something that is easy for a patient to go through.
At progression of disease, after being on an EGFR TKI [tyrosine kinase inhibitor], either as monotherapy or in combination, we have to reassess the patient, molecularly speaking. Depending on what TKI you usedif you use any of the first- or second-generation TKIs, or even if you used this novel combination of erlotinib plus ramucirumab—we rebiopsy the patient, in particular looking for a mutation calledEGFRT790M, for which osimertinib is the medication of choice. Basically, the patient will have the option to go through another tyrosine kinase inhibitor, another oral medication as a second-line therapy.
If the patient was placed on osimertinib up front, we already have another mutation that explained the resistance to osimertinib. Drug development for this particular mutation is in progress. We don’t have any medication for that particular genomic abnormality that is causing resistance to osimertinib, but we also know that those patients are also prone to develop other kinds of mechanisms of resistance that we may target in combination with either other agents or, perhaps, with osimertinib. That is the importance of a rebiopsy and reanalyzing all these patients who have, in particular, anEGFRmutation.
Transcript edited for clarity.
Case: A 63-Year-Old Woman With MetastaticEGFR+ NSCLC
Initial presentation
- A 63-year-old woman presented with persistent cough, and a 5-lb weight loss
- PMH/SH: former smoker, quit 25 years ago
- PE: Decreased breath sounds on auscultation in the right lower lobe
Clinical workup
- Labs: WNL
- PFT: FEV1/FVC 60%; DLCO 68%
- Chest X-ray showed a right lower lobe soft tissue mass
- Chest/abdominal/pelvic CT showed a 3.8-cm solid pulmonary mass in the right lower lobe; enlarged contralateral hilar and mediastinal lymph nodes; 3 small right adrenal lesions noted
- CT‐guided core needle biopsy of the lung mass revealed lung adenocarcinoma; lymph node biopsy showed grade 2 adenocarcinoma
- Contrast‐enhanced MRI of the head showed no evidence of brain metastases
- Molecular testing:EGFRexon 21 substitution L858R, ALK-, BRAF-, ROS1-, RET-, MET-, ERBB2-,PD-L1 TPS 14%
- Staging- T2aN3M1b - IVA; ECOG PS 0
Treatment
- Patient was started on erlotinib 150 mg PO qDay + ramucirumab 10 mg/kg IV
- Imaging at 3-month showed partial response with decrease in lung lesion
