Combination Immunotherapy Shows New Promise for Lung Cancer

By Matthew Tontonoz,

Wednesday, June 1, 2016

Lung cancer and immunotherapy expert Matthew Hellmann
Summary

Immunotherapy has emerged as a promising new treatment option for people with lung cancer. MSK scientists are conducting research to enable more patients to benefit from immunotherapies, at earlier stages. We spoke with MSK lung cancer and immunotherapy expert Matthew Hellmann to learn more.

Highlights
  • Immunotherapy drugs are currently approved as second-line treatment for non–small cell lung cancer.
  • MSK researchers are testing immunotherapy drug combinations as first-line treatment for advanced disease.
  • Compared with chemotherapy and targeted therapy, immunotherapies may offer more hope for durable, long-term remissions.

For people with lung cancer, immunotherapy has emerged as an important new treatment option. Drugs called immune checkpoint inhibitors that “release the brakes” on the immune system have produced remarkable results in some patients, offering hope to the more than 200,000 people in the United States who are diagnosed with lung cancer every year. 

Yet currently only a small group of patients respond to these drugs. Researchers believe that combining immunotherapy drugs may be one way to boost the number of responders. They would also like to give immunotherapy earlier in the course of the disease, including to patients with early-stage cancers and as first-line treatment for metastatic cancer. (Currently, immunotherapy drugs are approved for non–small cell lung cancer only as second-line treatment, after chemotherapy.)

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This week at the annual meeting of the American Society of Clinical Oncology (ASCO), Memorial Sloan Kettering’s Matthew Hellmann will present results from a phase I study of two immunotherapy drugs, nivolumab and ipilimumab, given in combination to patients with previously untreated advanced non­–small cell lung cancer. Nivolumab is a checkpoint inhibitor that targets an immune protein called PD-1, while ipilimumab targets one called CTLA-4.

We sat down with Dr. Hellmann to discuss how immunotherapy is changing the care of patients with this disease.

How would you describe the progress we’re making in immunotherapy for lung cancer?

What I think is remarkable is that, just a few years ago, nobody thought immunotherapy was relevant in lung cancer. Since 2012, there’s been this remarkable expansion of trials and data for PD-1 inhibitors. The result is that we now have a totally new class of drugs for the most common and deadliest type of cancer in the world.

Although the change in the field has been profound, not everyone benefits from these therapies. Only 15 to 20 percent of patients with lung cancer benefit from PD-1 blockade by itself. And so it prompts two major questions: How do we identify more precisely the people who should get PD-1 therapy? And then also how do we develop new immunotherapy combinations so that we can help more people?

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At ASCO, you’ll be presenting updated data from a clinical trial that combined a PD-1 inhibitor with another immunotherapy drug. How do the data look?

I think the data are really compelling. I hope the message that comes out of ASCO, both from this report and others, is that the initial successes of PD-1 inhibitors by themselves for patients with lung cancer are just the beginning. There is real promise in combination immunotherapy and I expect there will be opportunities for new molecules and new combinations to let more patients benefit from immunotherapy in the future.

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The patients in this study had no prior treatment, including chemotherapy. Are we looking at the end of chemotherapy for lung cancer?

I worry about the narrative “chemo is terrible.” I think that’s the wrong way to look at it. Immunotherapy is a really important, transformative addition to the options we have to help people with lung cancer. But sometimes it doesn’t work, and sometimes chemotherapy is the right thing for patients. The point is that you want a treatment that works, whatever it is. The more options we have and the more diversity of types of treatment we can use, the better off we all are.

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How will doctors determine which treatment is best to give in the first-line setting?

Several important clinical trials are ongoing now looking more closely at combination immunotherapies. In one phase II trial, everyone is getting the combination of ipilimumab plus nivolumab. A large phase III trial is comparing chemotherapy versus nivolumab by itself versus ipilimumab plus nivolumab. That trial is aimed at answering the question of what’s the best first thing to give somebody with lung cancer? Tissue samples are being collected, and the hope is that we will be able to understand how treatment responses relate to the underlying tumor biology. Eventually, the goal is to use characteristics of the tumor to choose the right therapy for the right patient.

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In lung cancer, are you seeing long-term responders to immunotherapy like we’ve seen in melanoma?

The longest cases we have are just over five years, from the phase I study of nivolumab that began in March 2011. There were two patients in that study who received treatment for two years who responded. They have been off treatment now for three years and are still doing well.

Only time will tell how long these responses can last, but we hope they are permanent. There are a handful of patients who, in a very literal way, have had their lives given back to them. That’s pretty cool.  

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What role do you see for immunotherapy as a treatment for lung cancer going forward?

The opportunity to cure someone with metastatic lung cancer has not previously been possible, so the fact that we now have some patients who have had a complete pathologic response at least gives you that nugget of hope. I think that what is transcendent about immunotherapy is the possibility of durability — something that generally isn’t seen with chemo or targeted therapies. Yet I also think it’s important that we remain vigilant about the possibility that these responses may not last forever and that we still have lots of work to do in order to increase the number of people we can help.

For more on open combination immunotherapy trials at MSK, see the following studies. In nonsmall cell lung cancer: 14-137, 15-251, 16-183, 13-197. In small cell lung cancer: 13-187.

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The phase I clinical trial of nivolumab and ipilimumab (CheckMate012) is being supported by Bristol-Myers Squibb, the maker of these drugs.

Comments

Hello
My father needs immunotherapy but we live in canada could he join the trial.

Dear Vince, the staff at our International Center can help answer your questions and either arrange for a medical records review with one of our specialists or if appropriate, make an appointment for an in-person visit. You may contact them directly at international@mskcc.org or for more information about our services for patients who live abroad, go to https://www.mskcc.org/experience/become-patient/international-patients.

To learn more about immunotherapy at MSK: https://www.mskcc.org/immunotherapy-msk

To browse through our clinical trials: https://www.mskcc.org/cancer-care/clinical-trials.

Thank you for reaching out to us.

A family member is looking at clinical trials for small cell lung cancer. I have noticed two types of trials involving nivolumab in combination with another drug. One trial uses nivolumab and ipilimumab and the other trial combines nivolumab and uloculumab . Are these trials similar in nature or does one show more promise than the other for small cell lung cancer.

Dear Lawrence,

Nivolumab and ipilimumab are two immunotherapy drugs known as checkpoint inhibitors that work to “take the brakes off the immune system,” allowing it to mount a stronger attack against cancer. This combination has shown promise in treating melanoma and lung cancer (both non-small cell and small cell lung cancer). Nivolumab and ipilimumab are antibodies.

Ulocuplumab is another type of antibody drug that works in a different fashion, by blocking a molecule that helps cells grow. Which combination is a better treatment for small cell lung cancer is not yet known, and that’s why they are being tested in clinical trials. We recommend your family member talk to their doctor about which trial might be better suited to their needs. Thank you for your comment.

My husband has non-small non scaumous lung cancer, has a HER2 mutation. He was on chemotherapy for 1.5 years, then tried the afatinib pill for 5 months, then 2 months of nivolumab, that did not work at all for him, then for 2 months was on Herceptin and docetaxel which worked but the side effects were really bad, had to stop it last week. Are there any trials at Sloan that he can qualify for? Would appreciate any response with any suggestions, advices.

Irene, MSK has a number of trials for the type of cancer your husband has. If you'd like to learn more about them and which ones may be right for him, you can make an appointment by calling 800-525-2225. You can go to https://www.mskcc.org/experience/become-patient/appointment for more information on making an appointment. Thank you for your comment.

Breast CA 2014, estrogen +, progesterone- Hert2 positive left breast mastectomy lymphectomy(5) removed Herceptin for 1 year. Aug 2016 treated 3 times for pneumonia then finally told cancer is back in left lung prognosis poor per onocoloist.
Told it was the same cancer as before

Dear Mechell, we are sorry to hear about your diagnosis. If you would like to make an appointment with one of our specialists to discuss possible treatment options, please call our Physician Referral Service at 800-525-2225. Thank you for reaching out to us.

My wife of 49 years had a CT scan in September that revealed a mass on her lower left lung. A biopsy done on November 4th confirmed a pulmonary adenocarcinoma, moderately differentiated, acinar pattern. TTF-1: Positive, Napsin A: Positive, CK7: Positive, p40: Negative.
She is Diabetic with Lupus as an underlying Autoimmune disease.
With her compromised immune system could she still be helped with Immunotherapy? Or does that reduce the effectiveness of the treatment below the already low percentile response rate?

Dear Michael,
The safety of immunotherapy for cancer in patients with an underlying autoimmune disease is uncertain. There is a theoretical concern that patients with certain autoimmune diseases may experience worsening of their autoimmune condition when given immunotherapy for cancer. For that reason, many clinical trials of experimental immunotherapies exclude patients with underlying autoimmune diseases. However, for drugs that are FDA approved, patients with autoimmune conditions may be eligible to receive immunotherapy for cancer and may benefit from it. For a patient with an autoimmune condition who also has cancer, the best thing for him or her to do is talk with a doctor about the risks and benefits of immunotherapy treatment. Thank you for your comment.

Hello,

My Mom has recently diagnosed with a non-small cell lung cancer after she did a liver biopsy which shows EGFR mutation positive. She also had a plural effusion and when when it was drained it was TTF-1 positive. She started the Tarceva three days ago.

My question is could my Mom benefit from the immunotherapy? Is she eligible to attend the trial? Is it early for her to start with the immunotherapy?

Not that my she had a Brest cancer triple possiive back in 2012. It was an early stage ( no lump nudes were involved) She had a mastectomy, Chemo therapy ( 4 rounds )and 1 year of herceptine.

Hi Amerah, we're sorry to hear about your mom's diagnosis. If she'd like to have a consultation at MSK to find out whether we have a trial that may be appropriate for her, she can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information on making an appointment. Thank you for your comment.

Hello, my husband diagnosed may 2015 stage IV NON-small cell Aden with mets to brain.
His history
6 rounds of carbo/taxol
2 round of alimta
Several sterotactical brain treatments
Wbt 10 rounds
30 rounds of radiation to chest
Hospitalized several times
Seizures
Blood clot to lung
Last episode very bad with a case of pneumonia while finishing last of his 30 chest treatments.
Since that episode he has been doing extermely well. He also has received two rounds of opdiva as he couldn't take the alimta anymore. Y question... they got him to 2 mg of decadron and started him on the immunotherapy. Recently they increased his steroids due to some headaches and nauseousness. We meet with his rad oncologist end of month for his brain. So now he is up to 4 mg of dex and doc won't do his treatment this week. I am upset as is he. We were excited about this treatment. I am reading conflicting information about the use of steroids, Dosage amounts and immunotherapy. Could you please clarify.

Thank you in advance.

Stacey.

Hi Stacey, because every case is different, we are not able to answer questions about individual medical treatments. If you have questions, we recommend you discuss this further with your husband's medical team. Best wishes to you, and thank you for your comment.

Is immunotherapy available for pleomorphic sarcoma. Initial tumor in the lef and patient received treatment: chemo, surgery and radiation. Tumor successfully removed from leg but one year later thetr are 9 nodules in lungs

MSK does have several clinical trials evaluating immunotherapy for various sarcoma types. You can learn more here: https://www.mskcc.org/cancer-care/clinical-trials/search?keys=immunothe…

If the sarcoma carries a type of mutation called an MMR defect, it may also be treatable with the immunotherapy drug pembrolizumab. This therapy is now approved by the FDA for any cancer that carries this mutation, and does not require participating in a clinical trial.

Thank you for your comment.

I am 55 yrs. old & I have small cell lung cancer. Diagnosed May 25, 2017. Have started my 3rd rd. of chemo (Cisplatin for 1st two - Carboplatin for 3rd -- hearing issue). Am working w/ Dr. for prophylactic radiation to help prevent spreading to the brain. Are there any trials out there??? I saw that my 5 yr. mortality outlook is 2%. Otherwise I am pretty healthy. HELP !!!
Heidi

Dear Heidi, we're very sorry to hear about your diagnosis. MSK has a number of trials for small-cell lung cancer. You can view the list here: https://www.mskcc.org/cancer-care/clinical-trials/search?keys=small+cel…

If you are interested in having a consultation to learn about these trials, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information on making an appointment. Thank you for your comment, and best wishes to you.

Help,
I live in Sweden and my mom was diagnosed with small cell lung cancer in September 2017. It was limited to the left lung, but it had spread within the lung and the main tumor invaded the pulmonary artery. She was given Carboplatin/Etoposide (x 3 days IV). Already after the first round of chemotherapy she was feeling great. The cough and the shortness of breath disappeared, and she was back to “normal”. We therefore thought that the chemo was working really well. The first CT scan (after 2 sessions) showed overall shrinkage. The second CT scan (after 4 sessions) still showed shrinkage, except the main tumor (the tumor that invades the pulmonary artery) which showed no shrinkage, but no growth either. Since the main tumor invades the pulmonary artery they did not want to give her radiotherapy. Instead they chose to change the chemotherapy and give her Topotecan (x 5 days oral) instead. After 2 sessions of Topotecan they told us that it looked like the main tumor has shrunk a little (they only did x-ray on the lungs). She is now on her 4th session (x 5 days oral), and she will do a CT scan in 2 weeks.
Now, the question is how to proceed after this! I have asked about immunotherapy, and the doctors (we have met quite a few) tell us that no immunotherapies exist for sclc. But I know that it does in other countries (or at least in the US). It scares me that the doctors do not know about this, when I have been able to find this by searching the Internet. I, who one year ago did not even know that a cancer called small cell lung cancer existed.
She has had very few side effects throughout the journey. She has not been ill or lost weight, and he values and blood counts have been good. I feel like we have to try EVERYTHING possible before we reach the end of this journey.
I have found that Opdivo+/-Yervoy is a standard second line (or beyond) treatment for sclc in the US. Is that right?
What determines whether the patient should be given the combination Opdivo/Yervoy (which seems to be working the best) or only Opdivo?
What are the chances of response, or at least stabilization (according to previous studies)?
Is Keytruda also a standard second line (or beyond) treatment for sclc in the US, or is it only used in trials?
Do you have any suggestions of how to proceed to be able to try immunotherapy even though we live in Sweden? The drugs (Opdivo, Yervoy, Keytruda) are used here, but only on nsclc patients I believe.
Thank you for your time!
Best regards,
Jenny

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