ONCAlert | Upfront Therapy for mRCC

Case 2: PD-L1+ and EGFR+ Lung Adenocarcinoma

Targeted Oncology
Published Online:1:07 PM, Thu June 20, 2019


EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Benjamin P. Levy, MD: Let’s move on to case 2. Let’s talk about a case in which a patient has PD-L1 [programmed death-ligand 1]–positive, EGFR-mutated lung cancer. This is a 70-year-old female. She presents to her PCP [primary care physician] with ongoing nausea, fatigue, and sporadic headaches. She has a past medical history of hypertension and hyperlipidemia but no smoking history. On physical exam, she has a moderately elevated blood pressure, 155/70 mm Hg, and auscultation reveals decreased breath sounds at the right lower lobe.

Her blood work is essentially unremarkable, and a chest, abdomen, and pelvis CT [computed tomography] scan reveals a 3.8-cm mass in the right lower lobe. She also has a 1.5-cm adrenal MET [metastasis] that’s confirmed on a PET [positron emission tomography] scan. An MRI [magnetic resonance imaging] of her brain is negative. She gets a CT-guided biopsy of the lung lesion that shows a grade 2 adenocarcinoma in the acinar pattern. Her PD-L1 TPS [tumor proportion score] is 70%, and her molecular testing is EGFR exon 19. Her final staging is a T2aN0M1b. She has stage IV, and has an ECOG [Eastern Cooperative Oncology Group] score of 1.

We’ve got an interesting case here, and this is 1 that we see a lot in tumor boards—a patient who is presenting relatively fit, who has never smoked with an oligometastatic disease, who has only 2 sites of disease, and who is both EGFR-positive as well as PD-L1-positive.

The management of patients with oligometastatic disease has altered over the past few years. I think we’re starting to think of things a little bit differently now and how they should be managed. I’ll ask Mickey and Anshu first as surgeon and radiation oncologist, the potential role for aggressive management. Let’s put aside the PD-L1 and EGFR right now. We’re trying to head in the direction of the potential role of metastasectomies or aggressive management of these areas, and for, dare I say, cure for a patient with stage IV disease—although that’s unlikely. Mick, do you want to discuss some approaches from a thoracic surgery standpoint?

Michael J. Walker, MD: The 1 thing I probably should mention is the change in the end staging that occurred with the 8th edition in the AJCC Cancer Staging Manual, in which M1a is really our pleural pericardial disease—a metastasis in the other lung, a satellite nodule. M1b is mono-metastatic. We always use the word oligo. Oligo means “few.” This is really a mono-metastatic lesion, right?

M1c is either multiple organs involved or multiple metastases in 1 organ, which is a little different here. This is definitely an M1b case; I see several a year. Historically, we know if these patients are mediastinal lymph node-positive, they do poorly. I think we really need to invasively make sure the mediastinum is OK. Performing an EBUS [endobronchial ultrasound] is my preferred route.

Benjamin P. Levy, MD: Lonny is shaking his head no.

Michael J. Walker, MD: I’m a surgeon, so typically I would probably have the adrenal gland removed first. If it was a brain metastasis, I would have that either removed or treated with radiation. But for the adrenal gland, we usually have a laparoscopic surgeon remove that. Afterward, we would probably give them chemotherapy and then do the lobectomy. Because if they’re going to MET out, then I don’t want to do a wasted operation. There’s no algorithm for the NCCN [National Comprehensive Cancer Network] Guidelines, but those are my personal thoughts.

Benjamin P. Levy, MD: Anshu, what are your thoughts? You bring up some important points, which is the timing of all this. Is chemotherapy first? If they don’t MET out, address each 1? Do you address 1, do chemotherapy, and then address the lung? Or do you just give them chemotherapy or just a TKI [tyrosine kinase inhibitor], because this patient is EGFR-positive. We’re in no-man’s land in terms of how to best manage these patients. Anshu?

Anshu K. Jain, MD: It’s a great case, and I agree with Mickey. I think that you have to approach disease states, whether they’re solitary metastases or oligometastatic disease, a little differently, and that’s how we do it in our practice. They’re coming in our clinic with a solitary metastasis, but we’ll typically recommend up-front management of the metastasis. I would also favor a minimally invasive surgical technique here. You get tissue and you deal with the metastasis as well. But I think if you’re starting to think about an oligometastatic state up front, sometimes in those cases we would think about managing the thoracic disease up front as a possibility, because we are all concerned that they might MET out. Or they might go straight to systemic therapy as a frontline option.

We have had cases in which we have dealt with the thoracic disease up front in the solitary metastasis state, but those are typically cases with the nonbrain metastases. So, there might be a liver metastasis or something of that nature. In many ways, we’re treating thoracic disease to give it a chance to show itself. Perhaps these patients will develop greater amount of metastatic disease, in which case the management after addressing the thoracic disease may change.

Benjamin P. Levy, MD: Yeah. I told you guys unfairly to ignore EGFR and PD-L1 as you’re having these comments, but much of this is contingent on the molecular underpinning. If this patient has an EGFR mutation, maybe you do start with a TKI and see how things go. Then if everything looks good, address each spot. I don’t think we have the timing sorted out here.

Transcript edited for clarity.


EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Benjamin P. Levy, MD: Let’s move on to case 2. Let’s talk about a case in which a patient has PD-L1 [programmed death-ligand 1]–positive, EGFR-mutated lung cancer. This is a 70-year-old female. She presents to her PCP [primary care physician] with ongoing nausea, fatigue, and sporadic headaches. She has a past medical history of hypertension and hyperlipidemia but no smoking history. On physical exam, she has a moderately elevated blood pressure, 155/70 mm Hg, and auscultation reveals decreased breath sounds at the right lower lobe.

Her blood work is essentially unremarkable, and a chest, abdomen, and pelvis CT [computed tomography] scan reveals a 3.8-cm mass in the right lower lobe. She also has a 1.5-cm adrenal MET [metastasis] that’s confirmed on a PET [positron emission tomography] scan. An MRI [magnetic resonance imaging] of her brain is negative. She gets a CT-guided biopsy of the lung lesion that shows a grade 2 adenocarcinoma in the acinar pattern. Her PD-L1 TPS [tumor proportion score] is 70%, and her molecular testing is EGFR exon 19. Her final staging is a T2aN0M1b. She has stage IV, and has an ECOG [Eastern Cooperative Oncology Group] score of 1.

We’ve got an interesting case here, and this is 1 that we see a lot in tumor boards—a patient who is presenting relatively fit, who has never smoked with an oligometastatic disease, who has only 2 sites of disease, and who is both EGFR-positive as well as PD-L1-positive.

The management of patients with oligometastatic disease has altered over the past few years. I think we’re starting to think of things a little bit differently now and how they should be managed. I’ll ask Mickey and Anshu first as surgeon and radiation oncologist, the potential role for aggressive management. Let’s put aside the PD-L1 and EGFR right now. We’re trying to head in the direction of the potential role of metastasectomies or aggressive management of these areas, and for, dare I say, cure for a patient with stage IV disease—although that’s unlikely. Mick, do you want to discuss some approaches from a thoracic surgery standpoint?

Michael J. Walker, MD: The 1 thing I probably should mention is the change in the end staging that occurred with the 8th edition in the AJCC Cancer Staging Manual, in which M1a is really our pleural pericardial disease—a metastasis in the other lung, a satellite nodule. M1b is mono-metastatic. We always use the word oligo. Oligo means “few.” This is really a mono-metastatic lesion, right?

M1c is either multiple organs involved or multiple metastases in 1 organ, which is a little different here. This is definitely an M1b case; I see several a year. Historically, we know if these patients are mediastinal lymph node-positive, they do poorly. I think we really need to invasively make sure the mediastinum is OK. Performing an EBUS [endobronchial ultrasound] is my preferred route.

Benjamin P. Levy, MD: Lonny is shaking his head no.

Michael J. Walker, MD: I’m a surgeon, so typically I would probably have the adrenal gland removed first. If it was a brain metastasis, I would have that either removed or treated with radiation. But for the adrenal gland, we usually have a laparoscopic surgeon remove that. Afterward, we would probably give them chemotherapy and then do the lobectomy. Because if they’re going to MET out, then I don’t want to do a wasted operation. There’s no algorithm for the NCCN [National Comprehensive Cancer Network] Guidelines, but those are my personal thoughts.

Benjamin P. Levy, MD: Anshu, what are your thoughts? You bring up some important points, which is the timing of all this. Is chemotherapy first? If they don’t MET out, address each 1? Do you address 1, do chemotherapy, and then address the lung? Or do you just give them chemotherapy or just a TKI [tyrosine kinase inhibitor], because this patient is EGFR-positive. We’re in no-man’s land in terms of how to best manage these patients. Anshu?

Anshu K. Jain, MD: It’s a great case, and I agree with Mickey. I think that you have to approach disease states, whether they’re solitary metastases or oligometastatic disease, a little differently, and that’s how we do it in our practice. They’re coming in our clinic with a solitary metastasis, but we’ll typically recommend up-front management of the metastasis. I would also favor a minimally invasive surgical technique here. You get tissue and you deal with the metastasis as well. But I think if you’re starting to think about an oligometastatic state up front, sometimes in those cases we would think about managing the thoracic disease up front as a possibility, because we are all concerned that they might MET out. Or they might go straight to systemic therapy as a frontline option.

We have had cases in which we have dealt with the thoracic disease up front in the solitary metastasis state, but those are typically cases with the nonbrain metastases. So, there might be a liver metastasis or something of that nature. In many ways, we’re treating thoracic disease to give it a chance to show itself. Perhaps these patients will develop greater amount of metastatic disease, in which case the management after addressing the thoracic disease may change.

Benjamin P. Levy, MD: Yeah. I told you guys unfairly to ignore EGFR and PD-L1 as you’re having these comments, but much of this is contingent on the molecular underpinning. If this patient has an EGFR mutation, maybe you do start with a TKI and see how things go. Then if everything looks good, address each spot. I don’t think we have the timing sorted out here.

Transcript edited for clarity.
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