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SCLC, Limited Disease

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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GRACE Cancer Video Library - Lung

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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Transcript

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.


Many Clinical Trial Options Exist for Small Cell Lung Cancer Patients

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Small cell lung cancer (SCLC) patients badly need new treatment options because the ones they have have not changed in almost 40 years. But a renewed interest in SCLC has led to an increase in research and the development of clinical trials testing new drugs. The links below beginning with “NCT” (National Clinical Trial) will provide more information that you can take to your doctor.

- Alisertib, an aurora kinase A inhibitor, is being studied with paclitaxel in the second line (NCT02038647); early trials using the drug showed activity and in particular, pre-clinical work has shown that tumors with MYC alterations may be most sensitive to Aurora Kinase inhibitors.

- Fibroblast growth factor receptor 1 (FGFR1) is amplified in 6% of small cell lung cancer and there are clinical studies evaluating drugs targeting the FGFR family members for SCLC patients, including the experimental drug JNJ 42756493 (NCT01703481).

- SCLC is known to have many abnormalities in DNA damage repair proteins and genes. One protein being studied is PARP, which is over-expressed in SCLC. There are active studies evaluating the PARP inhibitors, talazoparib and veliparib either alone or in combination with chemotherapy for the treatment of SCLC (NCT01286987, NCT01642251, NCT02289690, and NCT01638546). Olaparib, another PARP inhibitor, is being evaluated with temozolomide in the setting of a phase II clinical trial (NCT02446704).

The immune checkpoint inhibitors, nivolumab and pembrolizumab, have been FDA-approved for the treatment of non-small cell lung cancer. Early studies using these agents in SCLC have showed encouraging and prolonged response rates.  There are numerous studies using immune checkpoint inhibitors that are currently open or about to launch. These drugs are being studied as:

- Maintenance treatment (NCT02538666 and NCT02359019);
- In the second line setting (NCT02481830);
- With radiation therapy (NCT02402920); or
- After several lines of therapy (NCT01928394NCT02261220, and NCT02472977).

Recently, results from a phase I/Ib study showed impressive activity in the second- and third- line setting for an antibody drug conjugate, rovalpituzumab tesirine, especially in the subset of patients whose tumors had high expression of the delta-like protein 3, which the drug targets. Phase II studies with rovalpituzumab tesirine are planned and likely will be available in 2016. A phase I study evaluating a similar compound is actively recruiting patients (NCT02500914).  

The studies highlighted above do not represent an inclusive list, but they do show that there are many trials searching for better answers for small cell lung cancer. Hopefully, the findings from these studies will begin to change the prognosis for patients with this disease. 

Please consider a clinical trial at some point during your treatment.

 


GRACE Video

Radiation Management of Limited Stage SCLC

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GRACE Cancer Video Library - Lung

GCVL_LU-GA04_Radiation_Management_Limited_Stage_SCLC

 

Dr. Vivek Mehta, radiation oncologist, reviews the basic principles and treatment approach for limited stage small cell lung cancer, which combines chest radiation with concurrent chemotherapy.

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Transcript

Small cell cancer of the lung is a type of lung cancer. Small cell cancer of the lung come in two shapes and sizes, if you will. Limited stage disease is cancer that’s affecting only the chest, or what we think about in radiation oncology as sort of “the box,” if you will, and extensive stage disease is small cell cancer that started in the chest, that spread to other parts of the body — for example, the liver, the bone, or other tissues.

The treatment for limited stage disease is often to use a combination of chemotherapy and radiation treatment. The chemotherapy goes throughout your body, killing not only the cancer that you can see, but the cancer that you also could be hiding somewhere that’s too small to detect. The radiation is directed at the bulky cancer that’s within the chest. The radiation treatment is delivered Monday through Friday, generally over a period of five or six weeks. The treatment is used in combination because, when you do radiation alone, you don’t kill most of the cancer that’s hiding elsewhere in the body — when you do chemotherapy alone, there’s a high risk of the cancer coming back in the region that it started. When you combine the radiation and chemotherapy together, you have a much greater chance of eradicating every last cell. Eradicating the last cell is the hope in this whole cancer, because you’re trying to cure these patients.

We’ve done studies in terms of the timing of when it’s best to give the radiation, relative to the chemotherapy, and what we’ve learned is that, if you can get the radiation and the chemotherapy started at the same time early on, that’s actually more effective than doing chemotherapy first and having the radiation at the tail end of treatment. So, our preference here at this center is to treat everybody with upfront chemoradiation, when it’s possible, in patients that can tolerate it, with limited stage disease. We’re hoping, again, to try to cure as many of these patients as we possibly can.


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