Immune to Cancer: The CRI Blog




Dr. Dmitriy Zamarin Answers Questions About Ovarian Cancer and Immunotherapy after the 2021 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 ovarian cancer.

Dmitriy Zamarin, MD, PhD, a medical oncologist at Memorial Sloan Kettering Cancer Center, led the Ovarian Cancer and Immunotherapy session.

We followed up with Dr. Zamarin after the event to discuss additional questions from attendees.

If side effects are too severe, can I discontinue checkpoint inhibitor immunotherapy for some time and then resume it later?

Excellent question. This depends on the type and severity of the side effects. Some side effects (for example rash or moderate diarrhea) can be reversible with steroids and patients can be safely restarted on an immune checkpoint inhibitor afterwards. However, some side effects can be so severe that they pose risk to a patient’s life; in those cases, one would need to think carefully about the risks of resuming checkpoint inhibitor later.

For example, one of my patients had severe inflammation in the lungs that required mechanical ventilation in the ICU. Thankfully, she has fully recovered, but I would be very concerned about restarting immunotherapy for her.

Is there any effective immunotherapy that works for recurrent ovarian cancer? Any current trials?

There are no immunotherapies that are currently approved for recurrent ovarian cancer, with the exception of mismatch repair-deficient ovarian cancers (these are very rare). Unfortunately, immune checkpoint inhibitors, such as pembrolizumab and nivolumab, are not very effective on their own in ovarian cancer. A number of current clinical trials are currently exploring immune checkpoint inhibitors in combination with other drugs, including chemotherapy, PARP inhibitors, and other novel immunotherapies. There are also a number of trials that are targeting tumor cells directly (for example REGN4018) and some trials using adoptive T cell therapy.

Does immunotherapy work on recurrent cervical cancer?

PD-1 inhibitor (pembrolizumab) is approved for patients with recurrent cervical cancer in combination with chemotherapy or after progression on chemotherapy. This drug only works in patients whose tumors express PD-L1. Another drug called tisotumab vedotin, which targets cancer cells directly, was also recently approved for therapy of recurrent cervical cancer after progression on prior therapy.

Why does immunotherapy not work for ovarian cancer as much as other cancers?

This is a very good question. Ovarian cancers have very few mutations, which makes them more difficult to be recognized by the immune system. In addition, these cancers may have multiple other mechanisms by which they suppress the immune response. However, while immune checkpoint inhibitors do not work well against ovarian cancer, other immunotherapies such as adoptive cell therapies and tumor-targeted antibodies still carry a strong potential. In addition, combinations of immune checkpoint inhibitors with other drugs may make ovarian tumors more susceptible to immune checkpoint inhibitors.

I have ovarian/endometrial type cancer. My oncologist says CAR T cell therapy will be good for me next year because it's not time yet. Is that right?

CAR T cell therapy is not for everyone. In addition, CAR T cells are not approved for ovarian cancer and are only available on trials. Not everyone is eligible for such studies, because not every tumor has a target for that specific CAR T cell therapy. CAR T cells can also be associated with significant risks, including death. The decision to pursue CAR T cell therapy must be balanced against the patient’s overall disease status and availability of other standard drugs. For patients that have effective therapeutic options available, we typically don’t start with CAR T cells immediately; however, for patients who are unlikely to respond to standard treatments CAR T cells may be more appropriate (if such study is available).

At what point should immunotherapy be sought? I'm currently doing chemo for a reoccurrence and this is my 3rd line of treatment. Is this a backup plan or something to coincide with chemo?

We always recommend for patients to look for clinical trials, regardless of lines of treatment. For example, some trials don’t even allow patients with more than 3 prior lines of therapy. There is some evidence from other cancers that immunotherapy may work better earlier in the course.

What is your suggestion for a patient who has exhausted and progressed on all front line therapies including two exposures to PARP?  Many trials become exclusionary with so many rounds of treatment.

It is true that many trials are exclusionary, but there are quite a few trials that don’t put limits on prior lines of therapy. Unfortunately, this may require looking through multiple institutions to see what’s available.

How about the treatment of low-grade ovarian cancer? Do you know of any advances in immunotherapy for low-grade ovarian cancer?

Unfortunately, too few patients with low-grade serous ovarian cancer have been treated with immunotherapy to date for us to be able to draw conclusions of whether immunotherapy is effective for these cancers. No studies are trying to address immunotherapy specifically in low-grade serous ovarian cancers, although low-grade serous cancers are often eligible for the same trials as high-grade serous ovarian cancers.

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