Dr. Leena Gandhi Answers Questions About Immunotherapy for Lung Cancer from the 2020 CRI Virtual Immunotherapy Patient Summit

At the CRI Virtual Immunotherapy Patient Summit in October, patients and caregivers were eager to further their understanding of immunotherapy for lung cancer.

Leena Gandhi, MD, PhD, director of the Clinical Center for Therapeutic Innovation at Dana-Farber Cancer Institute, led the Lung Cancer and Immunotherapy Breakout Session.

We followed up with Dr. Gandhi after the event to discuss several more questions from attendees.

How long can a patient continue immunotherapy if scans show no sign of cancer?

Dr. Gandhi: There is no specific time. If scans show no sign of cancer, that is something we call a “complete response.” In many cases, that type of response will continue even if you stop the immunotherapy. Some patients will never have any cancer growth again. Some will show growth again over time, and studies show that the cancer can respond again if retreated with the same immunotherapy. A recent study suggested that continuing immunotherapy instead of discontinuing it may be beneficial, but there were many flaws in that study. Many patients included in the study had not had a response at the time they were discontinued. My own feeling is that it can be safe to discontinue, particularly if you have had a complete response, but you should remain under close supervision by your doctor.

What is a “PD-L1 score,” and how high does it need to be for a patient to benefit from immunotherapy? 

Dr. Gandhi: A PD-L1 score, as used in lung cancer, refers to the percentage of tumor cells that make a protein called PD-L1. This protein is normally made by immune cells, but cancer cells can make it, and it is one of the ways they can evade being killed by your immune system. PD-L1 expression can vary from 0% (about a third of lung cancer patients) to 100%.

For those who have more than 50% of their tumor cells expressing PD-L1, the chance of benefitting from immunotherapy is better than it is from chemotherapy. These patients can often be treated with immunotherapy instead of chemotherapy with better results. Even for those who express lower levels of PD-L1 (1-49%), there can be benefit from immunotherapy, but in these cases, there is a higher chance of benefit when combined with chemotherapy (or additional immunotherapies). 

Can you clarify whether immunotherapy is effective in lung cancer that has mutations like EGFR, ALK, or ROS1?

Dr. Gandhi: Patients with EGFR, ALK, or ROS1 alterations are often non-smokers and often have cancer cells that are less severely “altered” or different from normal cells than those that occur in smokers. As the number of alterations can correlate with the chance of being recognized as “foreign” and killed by your immune system, we don’t see as much benefit from anti-PD-1 immunotherapies on their own as in those who have cancers that are more “altered.”

Specifically, the chance of benefit may be lower and may not last as long. That said, everyone is different and some of these cancers can respond well. Also, it is possible that combining chemotherapy with immunotherapy may be just as effective in EGFR/ALK/ROS1 patients as others (studies are ongoing). We are learning that some combination therapies may be uniquely effective in such patients. For instance, a small study done in China combining a vaccine made up of a patient’s whole tumor with anti-PD-1 therapy showed that in some patients with a specific EGFR mutation, durable benefit could be achieved because a specific fragment of the altered EGFR was signaling the immune system to kill the cancer cells and the vaccine boosted this signal.

So, we are still trying to understand how best to use immunotherapy in EGFR/ALK/ROS1 patients. It may be that a combination of therapies can work very well.

Is it unusual to have "no evidence of disease" after six months of immunotherapy?

Dr. Gandhi: It is unusual. It is something we always hope for, but having “no evidence of disease” or a “complete response” happens in only a small percentage of patients treated with immunotherapy. Most patients who benefit have a more mixed picture, with some shrinkage but still “evidence of disease”—a “partial response.” A complete response is considered especially encouraging for the chances of long-term cancer control, but a partial response can also be long-lived.

I sometimes take high dose steroids to treat immunotherapy-related colitis. Is there a limit to how often or how long I can take these steroid courses? 

Dr. Gandhi: There is not a limit per se, however, the more important question is how serious the colitis is. If the colitis causes you to get sick enough to require hospitalization, that can be very dangerous, and even if steroids help, immunotherapy shouldn’t be continued because subsequent reactions could be as bad or worse. If the colitis is more minor, steroids could be used repeatedly, but while you are on them, you should not receive immunotherapy to treat your cancer.

Most small studies do not suggest that steroids limit your ability to benefit from immunotherapy (a few do), but we don’t know enough yet to limit these. This is a case-by-case decision you can discuss with your doctor.

High-dose steroids used frequently or for long periods can have other health consequences though, so these should be limited as much as possible. If you need frequent or prolonged dosing, you should talk to your doctor about the risks versus benefits of continuing the immunotherapy. We have seen that for some patients who develop immune-related toxicities related to immunotherapy, these can be associated with durable benefit, even if the immunotherapy is stopped. 

After successful treatment with immunotherapy and becoming disease-free, if my lung cancer comes back, would treatment with the same immunotherapy be effective in reaching the same result?

Dr. Gandhi: Yes, it can be. Studies in patients who stop immunotherapy after becoming disease-free (or having a partial response) suggest that re-responses can occur if no other intervening treatment used. However, that doesn’t happen in all patients as the cancer can change over time. That said, it is definitely a safe and worthwhile approach if you can be closely monitored by your doctor. 

Register for Part 2 of the CRI Virtual Immunotherapy Patient Summit