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SCLC, Extensive Disease and Recurrent

Denise Brock

Lung Cancer Video Library – SCLC – Novel Therapies In Small Cell Lung Cancer (SCLC): Lurbinectedin

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GRACE Cancer Video Library - Lung

 

H. Jack West, MD
President & CEO, GRACE

 

We are pleased to have GRACE’s Jack West, MD, Medical Director, Thoracic Oncology Program, Swedish Cancer Institute in Seattle, Washington, and President and CEO of GRACE bring 2017 updates to our Lung Cancer Video Library.  

In this latest video, Dr. West discusses exciting new advances in SCLC –  Novel Therapies In Small Cell Lung Cancer (SCLC): Lurbinectedin.  

 


 

 

 

 

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GRACE Video

Immunotherapy for Small Cell Lung Cancer

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GRACE Cancer Video Library - Lung

GCVL_LU-G03_Immunotherapy_Small_Cell_Lung_Cancer

 

Dr. Cathy Pietanza from Memorial Sloan Kettering Cancer Center reviews early trial data of immunotherapy agents for treatment of small cell lung cancer (SCLC).

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There has been a lot of excitement with immunotherapy in non-small cell lung cancer — nivolumab was recently approved for the treatment, in the third line setting, for squamous cell lung cancer, and has received NCCN designation to be used in adenocarcinoma. These treatments, as I said, target the immune system, and the way that I like to explain it is that, currently, the cancer is able to decrease the amount that the immune system works against it, and by using immune therapy inhibitors, the proteins and the two systems become disconnected, so that way the immune system can really attack the cancer.

In June of 2015, at our annual clinical oncology conference, we saw data for two agents – one was nivolumab, and that clinical trial was very early phase, it was only a phase one, it was really only looking to see if there was safety. There were two arms to that study — one arm received nivolumab by itself, which is one inhibitor against the immune system, and the other used nivolumab with ipilimumab. Ipilimumab is another type of inhibitor against the immune system. It’s believed that, maybe, two inhibitors may work better than one alone, and both arms showed that there was a very nice response rate to these drugs in small cell lung cancer, and that the patients who did respond had a long-term response duration. And, so, these are being evaluated in newer trials. In fact, there’s a maintenance trial that’s planned to start opening in January 2016 or so, that will be looking at immune therapies in the maintenance setting, which is something that’s never really been explored in small cell lung cancer — that’s if we use a drug after first line chemotherapy. The trial is going to be a placebo controlled trial, so patients will be on one of three arms: either placebo, or nivolumab, or nivolumab with ipilimumab.

In June of 2015, also at our large clinical oncology conference, pembrolizumab, another immune therapy inhibitor, was also shown to be beneficial in patients with small cell lung cancer. There are several trials planned with this drug, also, in the maintenance setting, and in the second line setting. So, second line would be, again, after first line chemotherapy, when the disease recurs; the trial that’s expected to open there is a trial of pembrolizumab, versus the standard, topotecan.


GRACE Video

Second Line Chemotherapy Options for SCLC

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GCVL_LU-GB02_Second_Line_Chemotherapy_Options_SCLC

 

Dr. Cathy Pietanza from Memorial Sloan Kettering Cancer Center discusses standard chemotherapy options for treatment of both sensitive and refractory small cell lung cancer (SCLC).

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The type of treatment that one receives in second line does depend on whether the disease is refractory to initial chemotherapy, or sensitive to initial chemotherapy. Once again, to define each of those: patients with refractory disease are those whose relapse or progression has occurred while they’re getting first line chemotherapy, or within 60 days of completing their last cycle — some studies have used up to 90 days; for patients with sensitive disease, as the term implies, they have had a good response to initial chemotherapy, have maintained that response for 60 to 90 days, post-completion of their last cycle. The terms refractory and sensitive will help us determine, again, what types of treatment to give, and how effective that treatment will be for them.

In general, patients with refractory disease are less likely to benefit from other treatments, but we will try, and patients who have sensitive disease usually can benefit from additional chemotherapy. It also tells us that one is more aggressive than the other. For patients with sensitive relapse, the time frame is very important — if patients recur after six months of receiving their last cycle of etoposide and platinum, they can then receive more etoposide and platinum; if not, the other options include topotecan, and CAV. Now, there was one phase three study, that compared topotecan and CAV, and found that they were about equal, and Topotecan actually had a better side effect profile, and so it was FDA approved, and it’s actually the only agent that’s FDA approved in the second line setting for small cell lung cancer. Additional studies then showed that both patients with sensitive, and refractory small cell lung cancer can benefit from topotecan, and therefore, even patients with refractory disease can get this agent. We also like to use CAV because it is an effective chemotherapy regimen — CAV is cyclophosphamide, doxorubicin and vincristine, and in patients, especially if we feel that they need a quick response, this generally elicits that.

The other option for patients with refractory disease is to receive best supportive care. Now, in either of these types of relapse, another very, very important option is a clinical trial, and the last two to three years has seen a flurry in clinical trials in small cell lung cancer, which is extremely exciting and was very much needed, and hopefully we will come across new agents for this disease. It is imperative that if patients are in good shape after their disease recurs, that they seek a clinical trial — it may benefit them, and it will hopefully benefit our knowledge of the disease and the treatment of future patients with the disease.


GRACE Video

Have Your Practices Changed Regarding Prophylactic Cranial Irradiation for Extensive Stage SCLC Patients?

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WCLC_2015_23_Practices_Changed_Prophylactic_Cranial_Irradiation_Extensive_Stage_SCLC

 

Drs. Ben Solomon, Leora Horn, & Jack West discuss whether the data highlighting cognitive deficits from whole brain radiation therapy (WBRT) for patients with brain metastases should change our recommendations for prophylactic cranial irradiation (PCI).

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Dr. West:  What about patients with extensive stage small cell lung cancer who don’t have brain metastases, and complete four or six cycles of chemotherapy, and still have a good performance status? We’ve seen conflicting results on the potential value of prophylactic cranial irradiation — some suggesting a significant survival benefit, some even suggesting harm, and a greater concern, I would say, throughout cancer, and certainly lung cancer, about cognitive side effects of brain radiation. So, where does that leave you in terms of what you say to a patient who’s finishing first line therapy and still has a good performance status; Leora?

Dr. Horn:  So, I do talk to patients about the data being fairly controversial. In my clinical experience, the patients who don’t get PCI — many of them do end up with brain metastases at some point.

Dr. West:  It’s very common in small cell.

Dr. Horn:  Yeah, and so I tell them it may delay it, or if it’s not something you want to do, we don’t have to do it at this point. But, I do worry about those patients that we’re not doing PCI [for] anymore, because the Japanese studies suggested, you know, maybe we shouldn’t.

Dr. Solomon:  Yeah, so one of the things that I’ve wondered about that Japanese study, which might make it different from the Slotman study, was the Japanese patients had pretty rigorous imaging of their brain, even prior to entry onto the study, so that study, to my recollection, gave PCI to patients who didn’t have brain metastases, and I wonder whether that might be an explanation for the differences seen. So, again, we have the discussion about PCI with the concerns about neurocognitive effects, but I wonder whether an alternative in someone who doesn’t want to have PCI is to have a policy of CNS imaging — but that’s not yet supported by data, but it might be something to think about.


GRACE Video

What Are Your Current Practices for Consolidation Chest Radiation for Extensive SCLC?

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WCLC_2015_22_Current_Practices_Consolidation_Chest_Radiation_Extensive_SCLC

 

Drs. Leora Horn, Ben Solomon, & Jack West debate whether results from a European trial of chest radiation after chemotherapy for extensive stage small cell lung cancer should lead to a change in treatment for this setting.

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Dr. West:  Not a lot here on small cell lung cancer, but there are still a couple of pretty controversial questions, including what the role is for consolidation chest radiation in patients who have residual chest disease after a good, but incomplete, response to chemotherapy. What are you guys doing in that situation? Is this something that has become a standard, or something that you often recommend, or at least discuss with patients, or is it still not something that has penetrated into common practice; Ben?

Dr. Solomon:  Yeah, so I must admit, even prior to the results with the Slotman study, which was published in the New England Journal — or, no, it was presented at ASCO — about thoracic radiation after chemotherapy, I used to worry about patients who had residual disease in their chest, because you worry that that’s a site at which they’re going to progress, and we’ve had discussions with our radiation oncology colleagues about treating that, almost preemptively. I think those data provide support to that, and provide an argument for delivering consolidation radiotherapy, if you like, for patients who have residual disease in their chest. There is additional toxicity from the treatment — the patients are pretty bashed up after their chemotherapy, so I think it’s a sort of individual discussion that we have with patients.

Dr. West:  And your thoughts?

Dr. Horn:  So, were doing the same. In the patients who tolerated chemotherapy well, and are doing well after chemotherapy, and had either bulky disease, or have residual disease, we will send them to discuss the thoracic radiation with the radiation oncology folks.


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