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Treatment of Operable Locally Advanced NSCLC

Panelists: Benjamin P. Levy, MD, Johns Hopkins Sidney Kimmel Cancer Center; Hossein Borghaei, DO, MS, Fox Chase Cancer Center; Roy S. Herbst, MD, PhD, Yale Cancer Center; Suresh S. Ramalingam, MD, Emory University School of Medicine; Naiyer A. Rizvi, MD, Columbia University Medical Center; Thomas E. Stinchcombe, MD, Duke Cancer Institute
Published: Wednesday, Feb 28, 2018



Transcript: 

Benjamin P. Levy, MD: It’s an exciting time for the field of thoracic oncology as the treatment landscape continues to change rapidly. In 2017, we experienced another groundbreaking year, with new drug approvals and practice-changing data. In this OncLive® Peer Exchange® panel discussion, my colleagues and I will discuss the clinical trials that will shape the way we treat our patients in 2018. We’ll provide context surrounding the data, discuss how to incorporate newly available agents into clinical practice, and share thoughts on the next advances coming to the clinic.

I am Dr. Benjamin Levy, assistant professor of oncology and clinical director of Medical Oncology at the Johns Hopkins Sidney Kimmel Cancer Center of Sibley Memorial Hospital in Washington, DC. I have the pleasure to be joined by this panel, of which include: Dr. Hossein Borghaei, chief of the Division of Thoracic Medical Oncology and associate professor in the Department of Hematology/Oncology at Fox Chase Cancer Center in Philadelphia, Pennsylvania; Dr. Roy Herbst, professor of medicine and chief of medical oncology at Yale Cancer Center in New Haven, Connecticut; Dr. Suresh Ramalingam, professor and deputy director of the Winship Cancer Institute at Emory University School of Medicine in Atlanta, Georgia; Dr. Naiyer Rizvi, professor of medicine and director of thoracic oncology at Columbia University Medical Center in New York, New York; and Dr. Thomas Stinchcombe, professor of medicine at Duke Cancer Institute in Durham, North Carolina. Thank you for joining us. Let’s begin.

I’d like to start with locally advanced non–small cell lung cancer, stage 3 lung cancer. This is roughly one-third of our patients, and we haven’t seen much movement in gains and outcomes over the past many years, up until recently with the PACIFIC trial. Before we talk about the PACIFIC trial, Tom, can you kind of walk us through how you approach these patients, some of the unmet needs and challenges we have, and how to manage these patients with stage 3 non–small cell lung cancer?

Thomas E. Stinchcombe, MD: I think that this is one of our more challenging diseases because the patient population is very heterogeneous and a lot of different paradigms are used. I think our approach is that if a patient has single-station N2 disease that’s microscopic, those are the patients we try and treat with induction chemotherapy and surgical resection. But if you have multiple microscopic N2 nodes involved or bulky N2 disease, you go into the chemoradiation paradigm with curative intent. I think there are 3 commonly used chemotherapy platforms: the weekly carboplatin and Taxol followed by consolidation/carboplatin, Taxol from the RTOG 0617 study and cisplatin, and etoposide and cisplatin and pemetrexed. I would say probably the majority of my patients get the weekly carboplatin and Taxol because I feel like I have a little bit more control and it’s a little bit better tolerated at this point. And then, like you said, I think the challenge is we’ve tried consolidation chemotherapy, we’ve tried consolidation docetaxel, we’ve tried vaccine as consolidation therapy.

Benjamin P. Levy, MD: Even targeted therapies.

Thomas E. Stinchcombe, MD: All of these things have not worked, and so it has really been a very frustrating field for us, and it’s one-third of our patients, like you said, so it’s a significant patient population.

Benjamin P. Levy, MD: And what percentage of your patients do you think are truly surgically resectable, and how is that decision made? Is it made up front by the surgeon and you stick with that decision? After an induction regimen, you go with it? How do you walk through that with a patient?

Thomas E. Stinchcombe, MD: So, I’m in a clinic where the thoracic surgeons and myself see them on the same day. We try and get the mediastinal staging, preferably with an EBUS (endobronchial ultrasound) at that time, and I have the surgeon say that this person is surgically resectable, making sure that there’s not a medical contraindication or a pulmonary function. Then what I’ve generally done is 2 cycles of cisplatin-based chemotherapy with a scan after cycles 2 and 4. And after cycle 4, we see them with the surgeons. Ideally, they do a mediastinoscopy at the time of the surgery, and if there’s persistent N2 disease, we know that that’s a very poor prognostic sign and that patient is unlikely going to benefit from a surgical resection. But if they have N2 clearance, then we try and do the resection at that point.

Benjamin P. Levy, MD: And do you give them consolidation chemotherapy after the surgery per the 0139 Intergroup trial?

Thomas E. Stinchcombe, MD: The 0139 trial used the chemoradiation, which is a reasonable paradigm, but I don’t employ that; there are some institutional preferences. I try and get all 4 cycles of the systemic therapy in prior to the operation, just because I think there’s a little bit better compliance. And then I think giving sometimes the postoperative platinum therapy can be very challenging in these patients.

Suresh S. Ramalingam, MD: I think what Tom said is important for our audience to keep in mind. If you have a patient with stage 3 disease, your decisions have to be made up front. If you have a patient who is surgically resectable, if you want to receive an induction chemotherapy or chemotherapy/RT and go to surgery, that’s fine. What is not a good approach is if you have a patient who is borderline resectable and you set out with the approach that you’re going to give chemotherapy/RT and see what happens. That never is a good strategy. You just have to decide up front. There may be situations where you think the patient is operable up front after induction, and it may not pan out and that’s OK. But don’t approach a borderline or unresectable situation as potentially salvageable after chemotherapy/RT.

Hossein Borghaei, DO, MS: I agree with that, and I think you have to make that decision up front.

Roy S. Herbst, MD, PhD: Because it’s curable disease.

Hossein Borghaei, DO, MS: Absolutely.

Roy S. Herbst, MD, PhD: This is why tumor boards are so important, as you said. I think all of our sites probably have a multimodality tumor board that meets at least once a week. We also have the fortune to be able to see the patients with our colleagues, surgeons, and the radiation oncologists.

Naiyer A. Rizvi, MD: And really the data are suggesting that you downstage patients with induction therapy. I think if the conversation of your tumor board is, “Let’s see what happens,” that means that they’re not resectable. I think that you are better off defining your path early on. Also, patients who are unresectable are not purely unresectable based on tumor location. Half of the patients that they combine modality therapy for are unresectable because of comorbidities, pulmonary functions, cardiac function. And so, you have technically resectable 3A patients, but the comorbidities preclude surgery.

Benjamin P. Levy, MD: And just a question, in terms of that unresectable patient, to the panel here. For those patients who may have challenging issues with comorbidities who are getting that weekly carboplatin/paclitaxel regimen, do we give consolidation after that, given that it’s a low dose and we’re not giving that systemic dose as we are with the cisplatin-containing regimens?

Hossein Borghaei, DO, MS: I do, for sure. If a patient can tolerate 6 or 7 weeks of concurrent chemotherapy/RT and they still have a reasonable performance status within normal parameters, I would try to get at least 1 or 2 cycles of the consolidation in. Now, you can argue what percentage of patients actually complete that, but I think my goal would be to get at least a cycle of that.

Suresh S. Ramalingam, MD: I used to do that a lot, but my enthusiasm to doing that has gone down after the Korean trial, which asked the question about the extra 2 cycles. And they didn’t see much of a benefit. So, in these days, if I give the concurrent chemoradiation, weekly carboplatin/paclitaxel, I’m happy to say we’re done with the treatments.

Benjamin P. Levy, MD: I always say some of my patients get the weekly regimen and I feel comfortable giving 2 consolidative doses. We just haven’t seen consolidation bear out in the trials; meta-analyses, Hoosier Oncology Group.

Hossein Borghaei, DO, MS: But those were a little bit different. Remember, on some of these studies, everybody got 2 full doses of cisplatin/etoposide per SWOG. In that case, when you’re giving full-dose chemotherapy, I completely agree with bypassing the consolidation because we don’t have data. It’s a different thing when you’re talking about weekly carboplatin/Taxol, and you know that the majority of these patients succumb to distant metastases, not so much local control—although the local control becomes an issue occasionally. So, for that reason, with the lower-dose chemotherapy, my argument has always been a little bit more systemic control where consolidated doses are appropriate. But definitely in the days whenever I used to do cisplatin/etoposide a lot, or if I do cisplatin/pemetrexed now, I’m not pushing people to get 2 or 3 additional cycles of full-dose chemotherapy. So, there is a difference in those studies.

Roy S. Herbst, MD, PhD: The data don’t really support. That said, even in testicular cancer, which is very platinum sensitive, you give 3 cycles. I think you have to be very selective, but ultimately, the way to cure these patients if they do have residual disease is going to be with molecular therapies and immunotherapies, which we’ll probably talk about later.

Hossein Borghaei, DO, MS: Yes, right.

Transcript Edited for Clarity 

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Transcript: 

Benjamin P. Levy, MD: It’s an exciting time for the field of thoracic oncology as the treatment landscape continues to change rapidly. In 2017, we experienced another groundbreaking year, with new drug approvals and practice-changing data. In this OncLive® Peer Exchange® panel discussion, my colleagues and I will discuss the clinical trials that will shape the way we treat our patients in 2018. We’ll provide context surrounding the data, discuss how to incorporate newly available agents into clinical practice, and share thoughts on the next advances coming to the clinic.

I am Dr. Benjamin Levy, assistant professor of oncology and clinical director of Medical Oncology at the Johns Hopkins Sidney Kimmel Cancer Center of Sibley Memorial Hospital in Washington, DC. I have the pleasure to be joined by this panel, of which include: Dr. Hossein Borghaei, chief of the Division of Thoracic Medical Oncology and associate professor in the Department of Hematology/Oncology at Fox Chase Cancer Center in Philadelphia, Pennsylvania; Dr. Roy Herbst, professor of medicine and chief of medical oncology at Yale Cancer Center in New Haven, Connecticut; Dr. Suresh Ramalingam, professor and deputy director of the Winship Cancer Institute at Emory University School of Medicine in Atlanta, Georgia; Dr. Naiyer Rizvi, professor of medicine and director of thoracic oncology at Columbia University Medical Center in New York, New York; and Dr. Thomas Stinchcombe, professor of medicine at Duke Cancer Institute in Durham, North Carolina. Thank you for joining us. Let’s begin.

I’d like to start with locally advanced non–small cell lung cancer, stage 3 lung cancer. This is roughly one-third of our patients, and we haven’t seen much movement in gains and outcomes over the past many years, up until recently with the PACIFIC trial. Before we talk about the PACIFIC trial, Tom, can you kind of walk us through how you approach these patients, some of the unmet needs and challenges we have, and how to manage these patients with stage 3 non–small cell lung cancer?

Thomas E. Stinchcombe, MD: I think that this is one of our more challenging diseases because the patient population is very heterogeneous and a lot of different paradigms are used. I think our approach is that if a patient has single-station N2 disease that’s microscopic, those are the patients we try and treat with induction chemotherapy and surgical resection. But if you have multiple microscopic N2 nodes involved or bulky N2 disease, you go into the chemoradiation paradigm with curative intent. I think there are 3 commonly used chemotherapy platforms: the weekly carboplatin and Taxol followed by consolidation/carboplatin, Taxol from the RTOG 0617 study and cisplatin, and etoposide and cisplatin and pemetrexed. I would say probably the majority of my patients get the weekly carboplatin and Taxol because I feel like I have a little bit more control and it’s a little bit better tolerated at this point. And then, like you said, I think the challenge is we’ve tried consolidation chemotherapy, we’ve tried consolidation docetaxel, we’ve tried vaccine as consolidation therapy.

Benjamin P. Levy, MD: Even targeted therapies.

Thomas E. Stinchcombe, MD: All of these things have not worked, and so it has really been a very frustrating field for us, and it’s one-third of our patients, like you said, so it’s a significant patient population.

Benjamin P. Levy, MD: And what percentage of your patients do you think are truly surgically resectable, and how is that decision made? Is it made up front by the surgeon and you stick with that decision? After an induction regimen, you go with it? How do you walk through that with a patient?

Thomas E. Stinchcombe, MD: So, I’m in a clinic where the thoracic surgeons and myself see them on the same day. We try and get the mediastinal staging, preferably with an EBUS (endobronchial ultrasound) at that time, and I have the surgeon say that this person is surgically resectable, making sure that there’s not a medical contraindication or a pulmonary function. Then what I’ve generally done is 2 cycles of cisplatin-based chemotherapy with a scan after cycles 2 and 4. And after cycle 4, we see them with the surgeons. Ideally, they do a mediastinoscopy at the time of the surgery, and if there’s persistent N2 disease, we know that that’s a very poor prognostic sign and that patient is unlikely going to benefit from a surgical resection. But if they have N2 clearance, then we try and do the resection at that point.

Benjamin P. Levy, MD: And do you give them consolidation chemotherapy after the surgery per the 0139 Intergroup trial?

Thomas E. Stinchcombe, MD: The 0139 trial used the chemoradiation, which is a reasonable paradigm, but I don’t employ that; there are some institutional preferences. I try and get all 4 cycles of the systemic therapy in prior to the operation, just because I think there’s a little bit better compliance. And then I think giving sometimes the postoperative platinum therapy can be very challenging in these patients.

Suresh S. Ramalingam, MD: I think what Tom said is important for our audience to keep in mind. If you have a patient with stage 3 disease, your decisions have to be made up front. If you have a patient who is surgically resectable, if you want to receive an induction chemotherapy or chemotherapy/RT and go to surgery, that’s fine. What is not a good approach is if you have a patient who is borderline resectable and you set out with the approach that you’re going to give chemotherapy/RT and see what happens. That never is a good strategy. You just have to decide up front. There may be situations where you think the patient is operable up front after induction, and it may not pan out and that’s OK. But don’t approach a borderline or unresectable situation as potentially salvageable after chemotherapy/RT.

Hossein Borghaei, DO, MS: I agree with that, and I think you have to make that decision up front.

Roy S. Herbst, MD, PhD: Because it’s curable disease.

Hossein Borghaei, DO, MS: Absolutely.

Roy S. Herbst, MD, PhD: This is why tumor boards are so important, as you said. I think all of our sites probably have a multimodality tumor board that meets at least once a week. We also have the fortune to be able to see the patients with our colleagues, surgeons, and the radiation oncologists.

Naiyer A. Rizvi, MD: And really the data are suggesting that you downstage patients with induction therapy. I think if the conversation of your tumor board is, “Let’s see what happens,” that means that they’re not resectable. I think that you are better off defining your path early on. Also, patients who are unresectable are not purely unresectable based on tumor location. Half of the patients that they combine modality therapy for are unresectable because of comorbidities, pulmonary functions, cardiac function. And so, you have technically resectable 3A patients, but the comorbidities preclude surgery.

Benjamin P. Levy, MD: And just a question, in terms of that unresectable patient, to the panel here. For those patients who may have challenging issues with comorbidities who are getting that weekly carboplatin/paclitaxel regimen, do we give consolidation after that, given that it’s a low dose and we’re not giving that systemic dose as we are with the cisplatin-containing regimens?

Hossein Borghaei, DO, MS: I do, for sure. If a patient can tolerate 6 or 7 weeks of concurrent chemotherapy/RT and they still have a reasonable performance status within normal parameters, I would try to get at least 1 or 2 cycles of the consolidation in. Now, you can argue what percentage of patients actually complete that, but I think my goal would be to get at least a cycle of that.

Suresh S. Ramalingam, MD: I used to do that a lot, but my enthusiasm to doing that has gone down after the Korean trial, which asked the question about the extra 2 cycles. And they didn’t see much of a benefit. So, in these days, if I give the concurrent chemoradiation, weekly carboplatin/paclitaxel, I’m happy to say we’re done with the treatments.

Benjamin P. Levy, MD: I always say some of my patients get the weekly regimen and I feel comfortable giving 2 consolidative doses. We just haven’t seen consolidation bear out in the trials; meta-analyses, Hoosier Oncology Group.

Hossein Borghaei, DO, MS: But those were a little bit different. Remember, on some of these studies, everybody got 2 full doses of cisplatin/etoposide per SWOG. In that case, when you’re giving full-dose chemotherapy, I completely agree with bypassing the consolidation because we don’t have data. It’s a different thing when you’re talking about weekly carboplatin/Taxol, and you know that the majority of these patients succumb to distant metastases, not so much local control—although the local control becomes an issue occasionally. So, for that reason, with the lower-dose chemotherapy, my argument has always been a little bit more systemic control where consolidated doses are appropriate. But definitely in the days whenever I used to do cisplatin/etoposide a lot, or if I do cisplatin/pemetrexed now, I’m not pushing people to get 2 or 3 additional cycles of full-dose chemotherapy. So, there is a difference in those studies.

Roy S. Herbst, MD, PhD: The data don’t really support. That said, even in testicular cancer, which is very platinum sensitive, you give 3 cycles. I think you have to be very selective, but ultimately, the way to cure these patients if they do have residual disease is going to be with molecular therapies and immunotherapies, which we’ll probably talk about later.

Hossein Borghaei, DO, MS: Yes, right.

Transcript Edited for Clarity 
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