ONCAlert | Upfront Therapy for mRCC

Case 1: Consolidation Therapy in Locally Advanced NSCLC

Targeted Oncology
Published Online:1:07 PM, Wed September 12, 2018


EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Benjamin P. Levy, MD:
I want to talk about the chemosensitization backbone that people are routinely using for stage III disease. Paul, what’s the practice at Memorial Sloan Kettering Cancer Center, and what would you do in this case? The case has already been laid out—cisplatin/etoposide with radiation. Is there ever room for carboplatin/paclitaxel?

Paul K. Paik, MD: In squamous lung cancer, in particular, we’re a bit limited in the regimens that we can give concurrently. It boils down to cisplatin/etoposide, if you’re going to give a cisplatin-based regimen, and weekly carboplatin/paclitaxel, if you’re going to give a non-cisplatin regimen. That’s about it. So, it’s really a decision as to whether or not the patient can tolerate cisplatin. That’s pretty much it. There’s not much else. There’s consolidation chemotherapy that you can give afterwards with these regimens, but the data, at least for the PACIFIC trial, suggest that the sooner you start durvalumab, the bigger the PFS [progression-free survival] benefit. And so, in terms of the radiosensitization component, it’s sort of whatever the patient can tolerate.

Benjamin P. Levy, MD: So you would give, in this case, cisplatin/etoposide?

Paul K. Paik, MD: Yes. In this particular case, if the patient could tolerate it—in terms of renal function, the lack of any hearing loss, and if the performance status was OK—then I think it’s reasonable to give that. Still, I think we think that cisplatin-based regimens in the early-stage setting have some modest advantage over carboplatin-based regimens. I think the question of consolidative or post-chemoradiotherapy and durvalumab—I was one of the first to not totally be enthusiastic about the PACIFIC trial.

Benjamin P. Levy, MD: I remember that.

Paul K. Paik, MD: Yes, last year. This is before we had an announcement about an OS [overall survival] benefit. I thought the trial was relatively uncontrolled, but there was additional granularity in the data that we could potentially see to get a sense as to whether or not the benefit that we were seeing in PFS and response rate, and this notion of distant metastatic disease, progression, might be confounded by a lack of control during that chemoradiotherapy phase. It’s important to note that in the trial, that chemoradiotherapy phase was uncontrolled. It was sort of dealer’s choice. People could give whatever they wanted, in terms of dose.

Benjamin P. Levy, MD: Yes, almost 25% got induction therapy.

Paul K. Paik, MD: Yes. And so, it makes a randomized trial difficult to interpret when a good component of the therapy is not controlled.

Anne S. Tsao, MD: The neoadjuvant consolidation, in all randomized trials, has not shown benefit...

Paul K. Paik, MD: Yes. It was sort of theoretical. It’s nice to be able to see all of the data that’s there. One of the concerns I had was with the radiation dosing, for example. They basically had a set of 3 different strata, but there was nothing terribly fine within that. In 1 strata, most patients got between a 54 Gy to 66 Gy dose, but that’s still a big range of radiation. The OS benefit, I think, pushes us, right? This is for a disease that has a very bad prognosis. For stage IIIB disease, the 5-year survival is, at best, 10%. Any amount of OS benefit is great.

Benjamin P. Levy, MD: So, this patient gets platinum/etoposide with radiation. Let’s say it’s a nice response. Would you give consolidation chemotherapy, Anne?

Anne S. Tsao, MD: I don’t.

Benjamin P. Levy, MD: You don’t give the chemotherapy?

Anne S. Tsao, MD: That is also 1 of the big questions that we get. Now, with the PACIFIC data, do we give 2 cycles of consolidation, or not? Or, do we just go to immunotherapy? Across the US, I think the trend is to do it just like PACIFIC trial—don’t give the consolidation. People always gave the consolidation because they thought weekly carboplatin/paclitaxel wasn’t enough systemic treatment.

Benjamin P. Levy, MD: Yes.

Anne S. Tsao, MD: But now that they have a systemic therapy, they’re OK with not going to consolidation chemotherapy. In my practice, I don’t give it anymore.

Benjamin P. Levy, MD: You give cisplatin/etoposide with radiation. The patient is doing well. Right then, you scan them with a CAT scan to make sure they have stable disease. And then, you move to durvalumab a week later?

Anne S. Tsao, MD: Routinely, when they complete concurrent chemoradiotherapy, I’ll scan them about 4 to 6 weeks later. Then, I start durvalumab.

Benjamin P. Levy, MD: OK. You don’t start it earlier?

Anne S. Tsao, MD: I know that there’s some suggestion that you should start within 2 to 4 weeks, but, I’ll be honest, these people are beat up. Some of them are elderly and they need a break.

Benjamin P. Levy, MD: This is interesting. The unique part of this program is to get different perspectives from different institutions. Paul, what would you do here?

Paul K. Paik, MD: Anne, that’s an excellent point. There’s a sort of signal that, maybe, if you give it earlier, it’s essentially better. But there’s a lot about the trial that’s not standard—getting a CT scan right at the end of chemoradiotherapy and jumping forward to additional systemic therapy. And you’re right—these patients are beat up and they’ve gone through a lot.

Anne S. Tsao, MD: They’re tired.

Paul K. Paik, MD: They’re tired, and now you’re saying, “Let’s start every 2 weeks…”

Anne S. Tsao, MD: For a year.

Paul K. Paik, MD: For a year, right.

Benjamin P. Levy, MD: So, what would you do here? What’s your timing?

Paul K. Paik, MD: For me, there’s no timing. The trial took a look between days 1 and 42, post-chemoradiotherapy. So, that’s technically the window, right?

Benjamin P. Levy, MD: Yes.

Paul K. Paik, MD: For me, you play it by ear. You talk to the patient about it and see how they’re feeling. If they’re not feeling well, you have them come back a couple of weeks later. Then, you see how they’re feeling. You sort of start it when you think they can tolerate it. This also, I think, gives you a period of time to observe whether or not there might be some immediate concern for pneumonitis, which might pop up.

Benjamin P. Levy, MD: I think these are excellent points. Generally, if the patient is beat up, I’ll wait and do the scan. For this patient, if they’re beat up, I’d give them 2 to 4 weeks. Then, I’ll do the scan. If things look good, I’ll then move on to consolidation with durvalumab. If they’re ready to go, or if I had to give them weekly carboplatin/paclitaxel and they’re not as beat up from that—there are times that I would offer weekly carboplatin/paclitaxel rather than cisplatin/etoposide—I may do the scan 1 or 2 weeks afterwards. I’d start treatment in the third week. I’d get them going if they’re very motivated. I think these are all nuances from the trial that we’re trying to take and apply to everyday practice.

Transcript edited for clarity.


EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Benjamin P. Levy, MD:
I want to talk about the chemosensitization backbone that people are routinely using for stage III disease. Paul, what’s the practice at Memorial Sloan Kettering Cancer Center, and what would you do in this case? The case has already been laid out—cisplatin/etoposide with radiation. Is there ever room for carboplatin/paclitaxel?

Paul K. Paik, MD: In squamous lung cancer, in particular, we’re a bit limited in the regimens that we can give concurrently. It boils down to cisplatin/etoposide, if you’re going to give a cisplatin-based regimen, and weekly carboplatin/paclitaxel, if you’re going to give a non-cisplatin regimen. That’s about it. So, it’s really a decision as to whether or not the patient can tolerate cisplatin. That’s pretty much it. There’s not much else. There’s consolidation chemotherapy that you can give afterwards with these regimens, but the data, at least for the PACIFIC trial, suggest that the sooner you start durvalumab, the bigger the PFS [progression-free survival] benefit. And so, in terms of the radiosensitization component, it’s sort of whatever the patient can tolerate.

Benjamin P. Levy, MD: So you would give, in this case, cisplatin/etoposide?

Paul K. Paik, MD: Yes. In this particular case, if the patient could tolerate it—in terms of renal function, the lack of any hearing loss, and if the performance status was OK—then I think it’s reasonable to give that. Still, I think we think that cisplatin-based regimens in the early-stage setting have some modest advantage over carboplatin-based regimens. I think the question of consolidative or post-chemoradiotherapy and durvalumab—I was one of the first to not totally be enthusiastic about the PACIFIC trial.

Benjamin P. Levy, MD: I remember that.

Paul K. Paik, MD: Yes, last year. This is before we had an announcement about an OS [overall survival] benefit. I thought the trial was relatively uncontrolled, but there was additional granularity in the data that we could potentially see to get a sense as to whether or not the benefit that we were seeing in PFS and response rate, and this notion of distant metastatic disease, progression, might be confounded by a lack of control during that chemoradiotherapy phase. It’s important to note that in the trial, that chemoradiotherapy phase was uncontrolled. It was sort of dealer’s choice. People could give whatever they wanted, in terms of dose.

Benjamin P. Levy, MD: Yes, almost 25% got induction therapy.

Paul K. Paik, MD: Yes. And so, it makes a randomized trial difficult to interpret when a good component of the therapy is not controlled.

Anne S. Tsao, MD: The neoadjuvant consolidation, in all randomized trials, has not shown benefit...

Paul K. Paik, MD: Yes. It was sort of theoretical. It’s nice to be able to see all of the data that’s there. One of the concerns I had was with the radiation dosing, for example. They basically had a set of 3 different strata, but there was nothing terribly fine within that. In 1 strata, most patients got between a 54 Gy to 66 Gy dose, but that’s still a big range of radiation. The OS benefit, I think, pushes us, right? This is for a disease that has a very bad prognosis. For stage IIIB disease, the 5-year survival is, at best, 10%. Any amount of OS benefit is great.

Benjamin P. Levy, MD: So, this patient gets platinum/etoposide with radiation. Let’s say it’s a nice response. Would you give consolidation chemotherapy, Anne?

Anne S. Tsao, MD: I don’t.

Benjamin P. Levy, MD: You don’t give the chemotherapy?

Anne S. Tsao, MD: That is also 1 of the big questions that we get. Now, with the PACIFIC data, do we give 2 cycles of consolidation, or not? Or, do we just go to immunotherapy? Across the US, I think the trend is to do it just like PACIFIC trial—don’t give the consolidation. People always gave the consolidation because they thought weekly carboplatin/paclitaxel wasn’t enough systemic treatment.

Benjamin P. Levy, MD: Yes.

Anne S. Tsao, MD: But now that they have a systemic therapy, they’re OK with not going to consolidation chemotherapy. In my practice, I don’t give it anymore.

Benjamin P. Levy, MD: You give cisplatin/etoposide with radiation. The patient is doing well. Right then, you scan them with a CAT scan to make sure they have stable disease. And then, you move to durvalumab a week later?

Anne S. Tsao, MD: Routinely, when they complete concurrent chemoradiotherapy, I’ll scan them about 4 to 6 weeks later. Then, I start durvalumab.

Benjamin P. Levy, MD: OK. You don’t start it earlier?

Anne S. Tsao, MD: I know that there’s some suggestion that you should start within 2 to 4 weeks, but, I’ll be honest, these people are beat up. Some of them are elderly and they need a break.

Benjamin P. Levy, MD: This is interesting. The unique part of this program is to get different perspectives from different institutions. Paul, what would you do here?

Paul K. Paik, MD: Anne, that’s an excellent point. There’s a sort of signal that, maybe, if you give it earlier, it’s essentially better. But there’s a lot about the trial that’s not standard—getting a CT scan right at the end of chemoradiotherapy and jumping forward to additional systemic therapy. And you’re right—these patients are beat up and they’ve gone through a lot.

Anne S. Tsao, MD: They’re tired.

Paul K. Paik, MD: They’re tired, and now you’re saying, “Let’s start every 2 weeks…”

Anne S. Tsao, MD: For a year.

Paul K. Paik, MD: For a year, right.

Benjamin P. Levy, MD: So, what would you do here? What’s your timing?

Paul K. Paik, MD: For me, there’s no timing. The trial took a look between days 1 and 42, post-chemoradiotherapy. So, that’s technically the window, right?

Benjamin P. Levy, MD: Yes.

Paul K. Paik, MD: For me, you play it by ear. You talk to the patient about it and see how they’re feeling. If they’re not feeling well, you have them come back a couple of weeks later. Then, you see how they’re feeling. You sort of start it when you think they can tolerate it. This also, I think, gives you a period of time to observe whether or not there might be some immediate concern for pneumonitis, which might pop up.

Benjamin P. Levy, MD: I think these are excellent points. Generally, if the patient is beat up, I’ll wait and do the scan. For this patient, if they’re beat up, I’d give them 2 to 4 weeks. Then, I’ll do the scan. If things look good, I’ll then move on to consolidation with durvalumab. If they’re ready to go, or if I had to give them weekly carboplatin/paclitaxel and they’re not as beat up from that—there are times that I would offer weekly carboplatin/paclitaxel rather than cisplatin/etoposide—I may do the scan 1 or 2 weeks afterwards. I’d start treatment in the third week. I’d get them going if they’re very motivated. I think these are all nuances from the trial that we’re trying to take and apply to everyday practice.

Transcript edited for clarity.
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