Diagnosis of Metastatic Lung Adenocarcinoma

Heather Wakelee, MD:We’ll be talking about a woman who’s 70 years old and Caucasian. She has been relatively healthy and has a distant smoking history, but it was heavy: she smoked 2 packs a day for 35 years. She presented to her primary care doctor because she had been losing weight without really trying to lose weight. She hadn’t changed her diet and she hadn’t changed her exercise, and I thought that was concerning. She had some gastroesophageal reflux disease, but otherwise, no other real problems.

Because of her smoking history and this weight loss, her primary care doctor is concerned and orders a chest x-ray. This, unfortunately, does show a mass in her right lung. This is followed by a CT scan, which confirms the presence of a 2.5-cm mass in the right lung, a significant amount of adenopathy in the mediastinum, smaller nodules that are scattered throughout both lungs, and a few nodules in the liver as well.

She is then sent to get a PET scan and that confirms that all of the sites seen on the CT scan are actually hypermetabolic and concerning for malignancy. Her brain MRI is negative. She has a biopsy done of the main mass in the lung and that confirms that this is indeed lung cancer, adenocarcinoma, which is confirmed by the positivity of a TTF1.

They do additional molecular testing, which we would hope is done.EGFRis negative,ALKis negative,ROS1is negative, andKRASis negative. She also has PD-L1 testing and that comes back at 35%. The patient has stage 4 adenocarcinoma of the lung, with metastases in the liver and lung. She has a PD-L1 expression level of 35% and no known driver mutations. So, she started on standard chemotherapy, a platinum doublet, with the addition of bevacizumab.

After 2 months on treatment, she comes back with a CT scan that shows there has been no progression of disease; everything is stable. Symptomatically, she actually feels better and has started to gain a little bit of that weight back.

In a patient with newly diagnosed metastatic lung cancer, there’s a range in how people do. I try not to talk with patients about how “This is the average” because I found that if you have a long discussion with someone and you bring in a number, that’s all that they remember hearing and they don’t hear the words around that number. So, we talk about ranges and how some people just don’t respond to treatment and have a short time, which could be just a few months. And then, some people have very good responses to treatment and live for a number of years. I have metastatic lung cancer patients I’ve been treating for over 10 years. So, we talk about those ranges of people. With this patient—who’s newly diagnosed, otherwise fit, without a really high disease burden—that would be the kind of discussion that we would have. I would assume, if she has a response to treatment, she likely has a few years. If her cancer’s refractory, treatment is going to be shorter. She also started with chemotherapy, and it was stable with her first imaging. She was tolerating it pretty well, and she was going to be able to continue.

Her PD-L1 expression was not negative, it was just less than 50%. So, she’ll be able to go on to immune therapy next, and we know that some people who get immune therapy have prolonged responses that can go on for 3, 4, or more years. She has got some reasons to be hopeful. We also know something about the molecular driver, which she doesn’t have—but we haven’t done the full panel. So, maybe she’s going to have aRETmutation or aMET exon 14skipping mutation or something else that’s targetable. That’s going to bring in more options.

When I think about her prognosis and how she’s going to do, she’s starting off with a limited disease burden and some response to treatment. She has many, many options moving ahead. There are a lot of different paths that she could be on.

Transcript edited for clarity.

• A 70-year-old Caucasian female presented with mild dyspnea and no chest pain.
• She has also experienced recent, rapid weight loss (>10 pounds in 1.5 months) without any changes in her diet or exercise pattern.
• She gave up smoking 7 years ago (2 packs per day for 35 years).
• Her medical history is unremarkable:
  • A few years ago, she was diagnosed with gastroesophageal reflux disease that was clinically and endoscopically confirmed.
  • She has no history of cancer in the family.
  • Her cardiac workup is negative.
• Her PS by ECOG assessment was 0.
• Chest x-ray showed a 2.5-cm lesion in her right lower lobe.
• CT scan of the chest and abdomen confirmed the presence of the lung mass in addition to numerous bilateral nodules, all about 5 to 9 mm, in the right upper and lower lobes and the left upper and lower lobes, as well as enlargement of hilar lymph nodes. In addition, 3 small nodules were seen in the liver, measuring 1 to 2 mm.
• PET/CT imaging showed 18F-FDG uptake in the lung mass, left hilar lymph nodes, and liver.
• MRI of the brain was negative for intracranial metastases.
• A core biopsy of the lung nodule was performed:
  • Its morphology and molecular phenotype (TTF-1-positivity) supported a diagnosis of lung adenocarcinoma.
  • Mutational testing showed absence of driver mutations (i.e., was negative forEGFR, ROS, andALK).
  • PD-L1 testing showed PD-L1 expression of 35%.
• The patient was diagnosed with stage IV metastatic NSCLC.
• The patient was started on therapy with a chemotherapy doublet and bevacizumab (Avastin).
• At her next follow-up 2 months later, her CT scan showed the right lung mass to be stable, with no new lesions. She has improved symptomatically.