ONCAlert | Upfront Therapy for mRCC

Case 3: Considerations for Second-Line Therapy in Stage IV NSCLC

Targeted Oncology
Published Online:12:41 PM, Wed September 26, 2018

Anne S. Tsao, MD: I want to reframe this case a little bit. Let’s say that instead of being a completely rapid progressor, she actually makes it through the triplet regimen for 4 cycles. Then, she goes on to maintenance pemetrexed/pembrolizumab and does pretty well. Then, you stop, for whatever reason. She comes back to your clinic a few months later. Do you ever rechallenge? Do you ever go back? What do you think about doing?

Paul K. Paik, MD: I have had a few cases in which this has come up. I rechallenge. In a setting where someone has responded to carboplatin/pembrolizumab, the reality is that you don’t really know what the active agent or agents are. You don’t know if it’s synergy, or if it’s the carboplatin/pembrolizumab that’s doing the lion’s share of the work, or if the pembrolizumab has no activity. That leaves you with trying to take a look at their course and make a rational decision about, “Well, maybe I should rechallenge them.”

Anne S. Tsao, MD: Ben, would you rechallenge, or would you think about rechallenging with another checkpoint inhibitor in that case?

Benjamin P. Levy, MD: I agree with Paul. I would be more comfortable going back to the regimen where the patient had garnered the benefit. That’s another discussion—whether these checkpoint inhibitors are all the same or not in their activity in non–small cell lung cancer, given some discrepant data that we’ve seen in similarly designed trials with different drugs. But, I would probably go back. If the patient had garnered a benefit, and if that benefit hadn’t been more than 6, 8, or 9 months and he/she had a treatment break, the question would be, would I go back to the pemetrexed/pembrolizumab regimen, or would I go back to the triplet and restart? I think this is where medicine becomes an art, not a science. We have to use our best judgement when determining what we think would be most meaningful for the patient. But, I’d probably rechallenge the patient. If this patient had never been off therapy, however, and had continued and then started to slowly putter along, I think this is a case where, again, I would consider second-line options with docetaxel and ramucirumab, even if they’re not rapidly progressing.

Anne S. Tsao, MD: Is that your favorite second-line regimen to go to after they’ve been on a triplet regimen?

Benjamin P. Levy, MD: Outside of the clinical trial for a fit patient, yes. But, I’m very ready to make a dose reduction with the docetaxel, and I don’t generally start at 75 mg/m2. I’ll start at 60 mg/m2, in most of my patients, with ramucirumab.

Paul K. Paik, MD: I agree. It’s my goal to go with modifications. Weekly docetaxel is better tolerated and is not less effective.

Anne S. Tsao, MD: What dose of weekly docetaxel do you use?

Paul K. Paik, MD: Really, 60 mg is worth considering. If you’re worried about additional toxicity, you can bring it down lower…

Anne S. Tsao, MD: Do you ever use nab-paclitaxel?

Paul K. Paik, MD: I’ve had difficulty getting it approved outside of the first-line setting. If someone has a hypersensitive reaction, or even if the steroid premedication is causing the issue with diabetes, I have gotten it approved. I have actually given ramucirumab in conjunction with nab-paclitaxel. It’s gone all right. There’s no reason to suggest that angiogenesis inhibition would not play well with other chemotherapy agents.

Anne S. Tsao, MD: The data suggests that it does, with what’s coming out, right? I think that we can close on this case, but I think what we’ve seen in lung cancer over the past 2 years is a rapid evolution in the frontline setting. We now have new therapies. I think that trend is going to extend into the salvage setting, where we begin to see that we have so many unanswered questions and a gap in knowledge, specifically in the immuno-refractory population. I think that there’s a lot of hope for these patients. Right now, in terms of salvage therapy, I agree that docetaxel/ramucirumab is a very reasonable option.

Transcript edited for clarity.

Anne S. Tsao, MD: I want to reframe this case a little bit. Let’s say that instead of being a completely rapid progressor, she actually makes it through the triplet regimen for 4 cycles. Then, she goes on to maintenance pemetrexed/pembrolizumab and does pretty well. Then, you stop, for whatever reason. She comes back to your clinic a few months later. Do you ever rechallenge? Do you ever go back? What do you think about doing?

Paul K. Paik, MD: I have had a few cases in which this has come up. I rechallenge. In a setting where someone has responded to carboplatin/pembrolizumab, the reality is that you don’t really know what the active agent or agents are. You don’t know if it’s synergy, or if it’s the carboplatin/pembrolizumab that’s doing the lion’s share of the work, or if the pembrolizumab has no activity. That leaves you with trying to take a look at their course and make a rational decision about, “Well, maybe I should rechallenge them.”

Anne S. Tsao, MD: Ben, would you rechallenge, or would you think about rechallenging with another checkpoint inhibitor in that case?

Benjamin P. Levy, MD: I agree with Paul. I would be more comfortable going back to the regimen where the patient had garnered the benefit. That’s another discussion—whether these checkpoint inhibitors are all the same or not in their activity in non–small cell lung cancer, given some discrepant data that we’ve seen in similarly designed trials with different drugs. But, I would probably go back. If the patient had garnered a benefit, and if that benefit hadn’t been more than 6, 8, or 9 months and he/she had a treatment break, the question would be, would I go back to the pemetrexed/pembrolizumab regimen, or would I go back to the triplet and restart? I think this is where medicine becomes an art, not a science. We have to use our best judgement when determining what we think would be most meaningful for the patient. But, I’d probably rechallenge the patient. If this patient had never been off therapy, however, and had continued and then started to slowly putter along, I think this is a case where, again, I would consider second-line options with docetaxel and ramucirumab, even if they’re not rapidly progressing.

Anne S. Tsao, MD: Is that your favorite second-line regimen to go to after they’ve been on a triplet regimen?

Benjamin P. Levy, MD: Outside of the clinical trial for a fit patient, yes. But, I’m very ready to make a dose reduction with the docetaxel, and I don’t generally start at 75 mg/m2. I’ll start at 60 mg/m2, in most of my patients, with ramucirumab.

Paul K. Paik, MD: I agree. It’s my goal to go with modifications. Weekly docetaxel is better tolerated and is not less effective.

Anne S. Tsao, MD: What dose of weekly docetaxel do you use?

Paul K. Paik, MD: Really, 60 mg is worth considering. If you’re worried about additional toxicity, you can bring it down lower…

Anne S. Tsao, MD: Do you ever use nab-paclitaxel?

Paul K. Paik, MD: I’ve had difficulty getting it approved outside of the first-line setting. If someone has a hypersensitive reaction, or even if the steroid premedication is causing the issue with diabetes, I have gotten it approved. I have actually given ramucirumab in conjunction with nab-paclitaxel. It’s gone all right. There’s no reason to suggest that angiogenesis inhibition would not play well with other chemotherapy agents.

Anne S. Tsao, MD: The data suggests that it does, with what’s coming out, right? I think that we can close on this case, but I think what we’ve seen in lung cancer over the past 2 years is a rapid evolution in the frontline setting. We now have new therapies. I think that trend is going to extend into the salvage setting, where we begin to see that we have so many unanswered questions and a gap in knowledge, specifically in the immuno-refractory population. I think that there’s a lot of hope for these patients. Right now, in terms of salvage therapy, I agree that docetaxel/ramucirumab is a very reasonable option.

Transcript edited for clarity.
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