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Beyond Progression in HER2-Positive Gastric/GEJ Cancers

Panelists: Johanna C. Bendell, MD, Sarah Cannon Research Institute; Ian Chau, MD, Royal Marsden Hospital; Yelena Y. Janjigian, MD, Memorial Sloan Kettering Cancer Center; Manish A. Shah, MD, Weill Cornell Medicine, New York-Presbyterian Hospital; Kohei Shitara, MD, National Cancer Center Hospital East, Japan
Published: Monday, Jul 31, 2017



Transcript:

Johanna C. Bendell, MD: Across the board, it seems like the thought in general is to use ramucirumab-based treatment, doublet or singlet, in the second-line setting. The question is, what do you do with HER2-positive disease? We’re going to come right back around again. Would you then give your HER2-positive second-line patient ramucirumab/paclitaxel after receiving trastuzumab-based therapy?

Yelena Y. Janjigian, MD: The answer is that you have to biopsy these patients to make sure they’re still HER2-positive, because if their loss of HER2 is noted, you should definitely not. And there are data presented at ASCO GI suggesting that continuation of trastuzumab beyond progression as opposed to—it wasn’t compared to. This not being a randomized study is important. So, definitely stopping trastuzumab altogether is the standard, but if you are able to continue it, it may be considered. Whether or not switching to ramucirumab is any inferior or superior to continuing trastuzumab beyond progression, we don’t know. And the standard, I would say outside of a clinical trial, is to do Taxol/ramucirumab.

Ian Chau, MD: Yes, because I think that some data, which Yelena alluded to, are retrospective—some of them are registry based—so I think there always could be potential bias into that and may potentially overestimate the benefit of continued trastuzumab. So, I think that in Japan, they have finished recruitment of a randomized study—although I understand it’s a randomized phase II study—of first-line trastuzumab-based chemotherapy, and then they were randomized to paclitaxel or paclitaxel plus continued trastuzumab. Is it called FELIX?

Kohei Shitara, MD: Exactly. We started this trial before the approval of ramucirumab, so we compare paclitaxel and paclitaxel/trastuzumab beyond progression for 90 patients after first-line therapy. We already finished recruitment, and we are waiting for the results. I agree with Yelena’s comment that to take a biopsy before second-line therapy is very important. We also have a similar experience of ROS/HER2 in approximately 20% of patients and their emergence over other oncogenic alterations such as MET or EGFR. I also have such patients. These patients might be good candidates for other clinical trials after second- or third-line chemotherapy. But regarding the RAINBOW data, we have a subgroup analysis, which was information submitted for their EMA, that shows a clear trend of improvement even for the HER2-positive disease with the ramucirumab. So, as a clinical practice, we use paclitaxel plus ramucirumab for HER2-positive disease.

Manish A. Shah, MD: So, I would just come back to the idea that HER2-positive gastric cancer is not the same thing as HER2-positive breast cancer. And we actually have more negative studies targeting HER2 in gastric cancer, 4 out of 5, compared with all the studies in breast cancer. I think that I would—really with a grain of salt—use trastuzumab beyond progression. If you were going to, a biopsy is absolutely important. But I think that you have actually active drugs—Taxol, ramucirumab, irinotecan, maybe a PD-1 inhibitor—and I’d hate for you not to use something that’s proven in that setting.

Transcript Edited for Clarity

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Transcript:

Johanna C. Bendell, MD: Across the board, it seems like the thought in general is to use ramucirumab-based treatment, doublet or singlet, in the second-line setting. The question is, what do you do with HER2-positive disease? We’re going to come right back around again. Would you then give your HER2-positive second-line patient ramucirumab/paclitaxel after receiving trastuzumab-based therapy?

Yelena Y. Janjigian, MD: The answer is that you have to biopsy these patients to make sure they’re still HER2-positive, because if their loss of HER2 is noted, you should definitely not. And there are data presented at ASCO GI suggesting that continuation of trastuzumab beyond progression as opposed to—it wasn’t compared to. This not being a randomized study is important. So, definitely stopping trastuzumab altogether is the standard, but if you are able to continue it, it may be considered. Whether or not switching to ramucirumab is any inferior or superior to continuing trastuzumab beyond progression, we don’t know. And the standard, I would say outside of a clinical trial, is to do Taxol/ramucirumab.

Ian Chau, MD: Yes, because I think that some data, which Yelena alluded to, are retrospective—some of them are registry based—so I think there always could be potential bias into that and may potentially overestimate the benefit of continued trastuzumab. So, I think that in Japan, they have finished recruitment of a randomized study—although I understand it’s a randomized phase II study—of first-line trastuzumab-based chemotherapy, and then they were randomized to paclitaxel or paclitaxel plus continued trastuzumab. Is it called FELIX?

Kohei Shitara, MD: Exactly. We started this trial before the approval of ramucirumab, so we compare paclitaxel and paclitaxel/trastuzumab beyond progression for 90 patients after first-line therapy. We already finished recruitment, and we are waiting for the results. I agree with Yelena’s comment that to take a biopsy before second-line therapy is very important. We also have a similar experience of ROS/HER2 in approximately 20% of patients and their emergence over other oncogenic alterations such as MET or EGFR. I also have such patients. These patients might be good candidates for other clinical trials after second- or third-line chemotherapy. But regarding the RAINBOW data, we have a subgroup analysis, which was information submitted for their EMA, that shows a clear trend of improvement even for the HER2-positive disease with the ramucirumab. So, as a clinical practice, we use paclitaxel plus ramucirumab for HER2-positive disease.

Manish A. Shah, MD: So, I would just come back to the idea that HER2-positive gastric cancer is not the same thing as HER2-positive breast cancer. And we actually have more negative studies targeting HER2 in gastric cancer, 4 out of 5, compared with all the studies in breast cancer. I think that I would—really with a grain of salt—use trastuzumab beyond progression. If you were going to, a biopsy is absolutely important. But I think that you have actually active drugs—Taxol, ramucirumab, irinotecan, maybe a PD-1 inhibitor—and I’d hate for you not to use something that’s proven in that setting.

Transcript Edited for Clarity
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