Cancer Topics - Contrasting Cases: EGFR Mutant NSCLC

Dr. Raja Mudad is a medical oncologist specializing in lung cancer at Florida Precision Oncology. In today's ASCO eLearning Podcast, Dr. Mudad will discuss two patient cases related to the treatment of advanced non-small cell lung cancer harboring an EGFR mutation. While the two cases are similar, the recommended treatments can be different. We hope you enjoy this episode. To hear the latest eLearning Podcast episodes as soon as they are available, please subscribe on Apple Podcasts [https://podcasts.apple.com/us/podcast/asco-elearning-weekly-podcasts/id1375021523] or Google Play [https://play.google.com/music/listen?u=0#/ps/Igjyhvqqrvuc5mjvlljhzkpvgeu]. We truly value your feedback, so please leave a review. To access our entire library of podcasts and other amazing eLearning content, visit elearning.asco.org [https://elearning.asco.org/homepage].

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Hello. My name is Raja Mudad. I'm a medical oncologist specializing in lung cancer. I work at Florida Precision Oncology, a practice dedicated to an academic approach in the treatment of cancer. Today, we compare two patient cases that relate to the treatment of advanced stage non-small cell lung cancer harboring an EGFR mutation. These two cases have similarities, yet the recommended treatments may be different.

Let us look at the cases. Patient case 1, our first patient case is Roberto. He is a 34-year-old man with stage 4 non-small cell lung cancer harboring an EGFR deletion 19 mutation.

The patient, a never smoker, presented with chest pain and was diagnosed with a pulmonary embolus. CT scan of the chest also demonstrated bilateral lung nodules. Biopsy revealed adenocarcinoma. Staging workup revealed multiple small brain metastases.

Patient case 2, our second patient case is Heidi. She is a 60-year-old woman with stage four non-small cell lung cancer with an exon 21 mutation in EGFR gene. She presented with a cough. A CT scan of the chest showed a left lung mass.

An endobronchial ultrasound guided biopsy revealed no evidence of mediastinal disease. And a biopsy was positive only in the mass showing adenocarcinoma. She was taken to surgery but found to have multiple pericardial nodules. No distant metastases were seen on the PET scan.

The two cases are clinically similar. Would any of the differences lead you to select a different treatment for each patient? Let's take a look.

The two patients have the exact disease, a similar stage, and mutations in the same EGFR gene. Their initial treatment is the same. The initial treatment in both cases, osimertinib, is considered the standard of care in the United States, with a median progression-free survival of 19 months. Roberto started on treatment with osimertinib, and the follow-up PET scan and brain MRI showed complete resolution of all of the abnormalities. In the second case, surgery was aborted, and the patient started on osimertinib.

About 1.5 years after Roberto started on osimertinib, progressive disease developed with a new adrenal mass, a new bone metastasis, and progression in the brain. He received stereotactic radiosurgery to the brain. A repeat biopsy of the adrenal mass revealed the same histology but with a MET amplification detected on next-generation sequencing. About eight months after starting osimertinib, Heidi developed progressive disease, and a repeat biopsy confirmed the same histology and the original EGFR mutation but no additional abnormalities.

As you can see, the two cases are similar at presentation. However, upon progression, both cases have peculiarities that make them different. Which differences in the two cases do you think may inform treatment choices? Would the differences lead your choice of treatment in a different direction, or would both patients receive the same treatment? If treatment is different, what is the difference that changes your choice of treatment?

The standard of care for non-small cell lung cancer with an EGFR mutation upon progression on first-line tyrosine kinase inhibitor is generally chemotherapy, possibly combined with immunotherapy. In non-small cell lung cancer with an EGFR mutation, there are multiple suggested mechanisms of resistance to osimertinib. These involve new mutations in the EGFR gene, alterations in parallel or downstream oncogenes, such as MET, KRAS, and PIK3CA, or histological transformation to small-cell carcinoma. MET amplification is a very common abnormality seen in those patients.

Upon progression, patients have several options, and their treatment should be directed based on the results of the repeat molecular evaluation. That is why it is important to repeat a biopsy on patients with disease progression. Nowadays, liquid biopsy is also helpful in detecting these abnormalities without the need for an actual biopsy.

Roberto can benefit from a MET-directed therapy using a tyrosine kinase inhibitor. He did receive stereotactic radiosurgery to the brain due to the presence of mild symptoms. He is clinically doing well, so the need to initiate immediate systemic cytotoxic chemotherapy is not urgent. In this patient, I would offer him an oral MET inhibitor and repeat his imaging in three months.

On the other hand, the second patient, Heidi, did not have an actionable mutation upon re-biopsy. The patient is best served by a clinical trial. However, if a trial is not available, or if she is not eligible, then systemic chemotherapy and immunotherapy would be the standard of care. In my practice, and based on the results of the IMpower 150 trial, the use of the combination of carboplatin, paclitaxel, atezolizumab, and bevacizumab is preferred. The subset analysis of the EGFR-positive patients in this trial favored the use of the quadruplet combination.

Thank you for listening to this episode of the ASCO eLearning Podcast. For more information on the treatment of non-small cell lung cancer, including additional patient cases and opportunities for self-evaluation, please visit the comprehensive eLearning center at elearning.asco.org.

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