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Treatment Options for Lung Cancer Mutations & Contingencies

Insights From: Yasushi Goto, MD, PhD, National Cancer Center
Published: Thursday, Jan 03, 2019



Transcript:

Yasushi Goto, MD, PhD:
We are now able to use the first-line osimertinib [Tagrisso] in Japan. We tend to use this first line because of its toxicity and cytokine release syndrome [CNS] activity. It’s, of course, difficult to tell whether there is benefit in sequential treatment, such as with adding afatinib [Gilotrif] to osimertinib.

We still try to use the platinum doublet with pemetrexed [Alimta] as well. There are also emerging data with carboplatin [Paraplatin] and paclitaxel [Abraxane] with bevacizumab [Avastin] and atezolizumab [Tecentriq]. We are finding whether that treatment is feasible with Japanese patients; however, there is the argument of whether the PD-L1 [programmed death-ligand 1] inhibitors are doing well in patients with EGFR mutations. We’re taking it step-by-step to assess whether they are effective. Of course there is a chance for those patients to take PD-L1, but in Japan right now we still use pemetrexed and carboplatin or cisplatin [Platinol] as second-line treatment.

For patients with ALK translocation, we are using alectinib [Alecensa] first line, which was developed in Japan. We lead the ALEX and J-ALEX trials. We are lucky to have early access to alectinib—we have lots of experience with it. We don’t know whether alectinib first line is superior to other treatments in terms of efficacy; however, the toxicity of alectinib was a miracle since we can prescribe it as treatment for hypertension.

As for ROS1 mutations in Japan, we can use only crizotinib [Xalkori], which we are fortunately accustomed to using because there was a time when it was used to treat ALK translocation. Even though the ROS1 population is small, we found that we are confident we can prescribe crizotinib and manage the toxicity so that the patient can really benefit.
We also do BRAF testing. By next year, we are trying to reimburse the next-generation sequencing system; eg, target sequencing. We’re trying to make those consistent. Right now, we only have access to BRAF, but soon we’ll have MET 14 skipping or HER2 as well. We already have some experience that it’s working. We believe that after they are reimbursed by the universal health system in Japan, the patients with those kinds of uncommon mutations will rise. After that, we think, many patients will be able to go directly to those kinds of treatment after [next-generation sequencing] testing.

Loxo Oncology is promising some drugs for RET fusion. In Japan they have a phase I trial under way. So I believe we will have access to RET inhibitors soon.

As for second-line treatments of EGFR TKIs [tyrosine kinase inhibitors], we have pemetrexed with platinum doublet; however, in Japan, as in many countries, there are a lot of elderly who suffer from EGFR-mutation stage I cancer. In those patients, it’s difficult because we started with EGFR TKI treatments, on which they were doing well. Most of the patients using the EGFR TKI treatment were given it as supportive care before the emergence of the mutation.

After the relapse of the EGFR TKI, we now have to think about whether they have already experienced EGFR TKI mutation. She was doing well even with gland cancer, but she was over 85—should we give the platinum doublet? That’s too difficult of a decision. Maybe we should administer pemetrexed [Alimta], but we really have to think about the toxicity and clinical benefit to those kinds of patients. It is difficult to get evidence in the elderly regarding low-performance status.

Of course, we are waiting for the approval of the triplet regimen of platinum doublet with pembrolizumab and atezolizumab; however, we have a concern that after combination therapy, it’ll be difficult for us to find biomarkers, which means, if you give it once, some patients will benefit, but some will not. It’s a challenge for us to find more effective combination treatments.

Transcript Edited for Clarity.
 

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Transcript:

Yasushi Goto, MD, PhD:
We are now able to use the first-line osimertinib [Tagrisso] in Japan. We tend to use this first line because of its toxicity and cytokine release syndrome [CNS] activity. It’s, of course, difficult to tell whether there is benefit in sequential treatment, such as with adding afatinib [Gilotrif] to osimertinib.

We still try to use the platinum doublet with pemetrexed [Alimta] as well. There are also emerging data with carboplatin [Paraplatin] and paclitaxel [Abraxane] with bevacizumab [Avastin] and atezolizumab [Tecentriq]. We are finding whether that treatment is feasible with Japanese patients; however, there is the argument of whether the PD-L1 [programmed death-ligand 1] inhibitors are doing well in patients with EGFR mutations. We’re taking it step-by-step to assess whether they are effective. Of course there is a chance for those patients to take PD-L1, but in Japan right now we still use pemetrexed and carboplatin or cisplatin [Platinol] as second-line treatment.

For patients with ALK translocation, we are using alectinib [Alecensa] first line, which was developed in Japan. We lead the ALEX and J-ALEX trials. We are lucky to have early access to alectinib—we have lots of experience with it. We don’t know whether alectinib first line is superior to other treatments in terms of efficacy; however, the toxicity of alectinib was a miracle since we can prescribe it as treatment for hypertension.

As for ROS1 mutations in Japan, we can use only crizotinib [Xalkori], which we are fortunately accustomed to using because there was a time when it was used to treat ALK translocation. Even though the ROS1 population is small, we found that we are confident we can prescribe crizotinib and manage the toxicity so that the patient can really benefit.
We also do BRAF testing. By next year, we are trying to reimburse the next-generation sequencing system; eg, target sequencing. We’re trying to make those consistent. Right now, we only have access to BRAF, but soon we’ll have MET 14 skipping or HER2 as well. We already have some experience that it’s working. We believe that after they are reimbursed by the universal health system in Japan, the patients with those kinds of uncommon mutations will rise. After that, we think, many patients will be able to go directly to those kinds of treatment after [next-generation sequencing] testing.

Loxo Oncology is promising some drugs for RET fusion. In Japan they have a phase I trial under way. So I believe we will have access to RET inhibitors soon.

As for second-line treatments of EGFR TKIs [tyrosine kinase inhibitors], we have pemetrexed with platinum doublet; however, in Japan, as in many countries, there are a lot of elderly who suffer from EGFR-mutation stage I cancer. In those patients, it’s difficult because we started with EGFR TKI treatments, on which they were doing well. Most of the patients using the EGFR TKI treatment were given it as supportive care before the emergence of the mutation.

After the relapse of the EGFR TKI, we now have to think about whether they have already experienced EGFR TKI mutation. She was doing well even with gland cancer, but she was over 85—should we give the platinum doublet? That’s too difficult of a decision. Maybe we should administer pemetrexed [Alimta], but we really have to think about the toxicity and clinical benefit to those kinds of patients. It is difficult to get evidence in the elderly regarding low-performance status.

Of course, we are waiting for the approval of the triplet regimen of platinum doublet with pembrolizumab and atezolizumab; however, we have a concern that after combination therapy, it’ll be difficult for us to find biomarkers, which means, if you give it once, some patients will benefit, but some will not. It’s a challenge for us to find more effective combination treatments.

Transcript Edited for Clarity.
 
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