Post-Conference Perspectives: Updates on the Treatment of EGFR Mutant Early-Stage and Advanced NSCLC - Episode 3

ADAURA and Selecting Adjuvant Therapy in EGFR Mutant Early-Stage NSCLC

Dr Mok finishes our discussion on the ADAURA trial, and Dr Peters delves into selecting the right adjuvant therapy for a patient with early-stage EGFR mutant NSCLC.

Tony S.K. Mok, MD: Close to 30% of the patients with EGFR mutation will eventually end up with CNS [central nervous system] metastases. For this group of patients, there’ll be resectable lung cancer, so their CNS status has to be clear upon enrollment. The chance of having a CNS event is about 2%, which is relatively low. I think the preliminary data is suggestive that it may work by actually reducing the CNS recurrence. Now, on the other hand, we do have a lot of CNS data from the stage 4 disease. The intracranial response rate is about 60% to 70% with the median progression-free survival intracranially up to 10 to 11 months. Based on the efficacy data based on the molecular structure and the stage 4 diseases, there’s a good chance that it may prolong prophylactic effect on the brain.

There are some data in the original paper, but it was not a comprehensive 1. Overall, there is no significant negative impact on the quality of life. Certainly, all of these patients have resectable lung cancer. Therefore, the disease itself does not affect their quality of life. It is actually a neutral with the significant benefit in long-term.

Solange Peters, MD, PhD: Adjuvant therapy with osimertinib [Tagrisso] follows basically the ADAURA trial design. Osimertinib was offered in ADAURA. At that time, we were using the seventh TNM classification, which was randomizing patients with classical EGFR mutation. Elision of exon 19 or L858R in exon 21. This patient had to have the good performance status and had to receive chemotherapy according to institutional and local standards of care. These are the patients who might qualify for adjuvant osimertinib. Primary end points in the trial design high establishes the rule of 3 years of osimertinib in stage 2 and stage 3a disease and not in stage 1b, which were there as the secondary end point and not the primary end point. It’s a very firm yes for establishing this osimertinib in the adjuvant setting for patients with stage 2 and 3 in non-small cell lung cancer with adjuvant or without adjuvant chemotherapy. Following local guidelines and classical exon 19, 21 EGFR mutations. It remains a freedom of investigation and must [be] defined at the discretion of the investigator. This same strategy can be extended to stage 1b, according to the seventh TNM classification. Today, there is less solid data. In most other countries where the registration and the reimbursement has been established for adjuvant osimertinib, the reimbursement has gone from stage 1b to stage 3a. That’s something that is part of the oncology and the choice of the investigator.

The completely resected non-small cell lung cancer usually defines a population of patients who are pretty fit because they are operable. For most of these patients, they at least have a decent performance status. However, some of these patients do not qualify for adjuvant chemotherapy. This might be because of age, organ deficiency, or contraindication for chemotherapy because of some organ dysfunction—preexisting organ dysfunction. Some of the resected patients have contraindications for chemotherapy. However, it’s less likely to have a contraindication for osimertinib. The bottlenecks, in this chemotherapy, followed by osimertinib is more the chemotherapy than the osimertinib. There are a few patients who present contraindication for osimertinib. Therefore, I would say this is to be delivered to all patients in this adjuvant setting with stage 1b maybe, 2, and 3a EGFR-mutated non-small cell lung cancer that is completely resected. Of course, you have to have an educated discussion for stage 1b disease. Fragile patients may be reluctant to take multiple pills per day for 3 years. Basically, I would say there are very few patients with contraindication. What was interesting in ADAURA was the benefit of osimertinib even in patients not receiving chemotherapy. I would say, irrespective of the delivery of chemotherapy. It doesn’t mean chemotherapy is not useful. Chemotherapy is established. But it means that osimertinib still has a benefit if the patient could not receive chemotherapy. I would therefore say the bottleneck is not osimertinib, but chemotherapy. Osimertinib can be delivered to almost all patients regardless of the age most of the time. Maybe the only situation that osimertinib imposed problems was few patients developed inflammatory lung disease, or some kind of pneumonitis. This might make you stop osimertinib treatment at some point. But in our Caucasian patients, I must say I almost never observed it.

This transcript has been edited for clarity.