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Lung Cancer: Immune Therapies Take Center Stage

Richard Frank, M.D.

It is perhaps the holy grail of treating advanced cancer: Harnessing a patient’s own immune system to successfully fight their cancer. No chemotherapy. No radiation. No nausea, vomiting, hair loss or infection. Achieving this end has eluded cancer scientists and physicians for decades despite the expenditure of billions of dollars in research. But this seemingly endless dark tunnel has finally found the light, in the name of a class of drugs that attach to molecules called “PD-1″ and “PD-L1.”

PD stands for programmed cell death receptor and was discovered by scientists studying how our immune system gets turned on and off. PD-1 is typically found on immune cells (called T-cells) that try to attack cancerous tumors in our bodies. If PD-1 is the ‘lock,’ then its ‘key’ is PD-L1 (L stands for “ligand”). PDL-1 is present on the outer surfaces of many cancer cells. But when PD-1 engages PD-L1, this lock and key system turns OFF the invading immune cells! The immune attack is disabled. This is one of the main reasons our immune systems fail to fight cancer.

The new findings, reported at this year’s American Society of Clinical Oncology meeting, show that the drug nivolumab (also called Opdivo), which blocks the ability of PD-1 to bind PDL-1, shrank lung cancer in more cases than did the chemotherapy drug docetaxel (Taxotere) and led to greater survival rates at 1 year (51% for nivolumab vs 39% for docetaxel). These results are in patients who have “non-squamous carcinoma” of the lung and previously received chemotherapy treatments. Non-squamous carcinoma is the most common type of lung cancer and includes the adenocarcinoma, large-cell carcinoma and other subtypes. Hopefully, the US Food and Drug Administration will soon approve Opdivo for the “second-line” treatment of this form of lung cancer. But there is more to this story.

Opdivo has already been approved recently by the FDA for the treatment of “squamous” lung cancer, the second most common type of lung cancer. Again, this approval is for patients who received chemotherapy as their first treatment. Now, oncologists can prescribe Opdivo instead of another chemotherapy as the second-line treatment for squamous lung cancer.

Both non-squamous and squamous carcinoma are types of non-small cell lung cancer. But what about small-cell lung cancer (SCLC), the third most common type of lung cancer but the most difficult to cure? Data presented at the ASCO meeting indicate that Opdivo also has some activity against SCLC, although less than for the other types of lung cancer. The results of ongoing studies are awaited to determine if Opdivo is an effective therapy for SCLC.

I should add that Opdivo is one of a host of new drugs in development targeting PD-1 or PDL-1. Pembrolizumab (Keytruda) also targets PD-1 and is approved to treat advanced melanoma; it will likely also receive FDA approval to treat lung cancer. These drugs are being tested in virtually every type of cancer.

This is of course very good news. So, what’s the bad news? The new immune therapies only benefit a fraction of lung cancer patients (especially those whose tumors express high levels of PDL-1) and they are still not a cure. There can be immune-related side effects requiring high doses of steroid drugs. And they are not cheap.

In order to improve the effectiveness of PD-1 and PD-L1 targeting drugs, they are being combined with other treatments, such as chemotherapy and different immune therapies. They are also being tested as the first-line treatment of lung cancer, without chemotherapy. These clinical trials are occurring throughout the world including at the Western CT Health Network.

Undoubtedly we are just beginning a new era in the treatment of lung cancer. But it certainly does look very promising!

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