Q&A on Neuro-Ophthalmic Adverse Effects of Molecularly Targeted Cancer Drugs

Starting with the approval of rituximab in 1997, molecularly targeted cancer drugs have transformed the way cancer treatment is approached. However, the new drugs are not without risks. After noting the unique toxicity profiles of many of the new cancer drugs, Duke’s April Salama, MD, a medical oncologist, and M. Tariq Bhatti, MD, the chief of neuro-ophthalmology, conducted a comprehensive review of the neuro-ophthalmic adverse effects of monoclonal antibodies, immune checkpoint inhibitors, and small-molecule kinase inhibitors. Here, they summarize some of their observations.

How has the cancer treatment landscape changed in recent years?
Salama: Not too long ago, many chemotherapeutic agents were nonselective and had significant toxicity. But in the past 2 decades, there have been amazing advances in the development of molecularly targeted cancer therapies, enabled by our improved understanding of the molecular and genetic machinery of oncogenesis. These new, selective therapies have really helped improve survival rates, especially in patients with more advanced cancer who otherwise would have had a very poor prognosis.

What are some of the challenges associated with these new therapies?
Salama: We’re learning that just because something is a targeted therapy doesn’t mean it can’t have adverse effects, it’s just that they’re different. Whereas chemotherapies had a lot of commonalities in terms of adverse effects—nausea, vomiting, and hair loss, for example—these targeted therapies all have different targets, so they can have really different, rare side effects.

Bhatti: Part of the problem is that we still don’t truly understand how the immune system works, so we can’t always predict how it will respond to a new drug. And many of these adverse effects were not appreciated during the clinical trials. It was only once the drugs were used in clinical practice that we realized some of the toxicities that could occur.

How have these new adverse effects changed the management of cancer?
Salama: These therapies are more effective at treating advanced cancers—we’re now starting to talk about survivorship in patients with advanced cancers who just 5 years ago had few treatment options. But that also means that these patients may be living longer with adverse effects, some of which don’t respond well to simply holding the drug. Rather, management requires specific intervention, so I think we’re going to start seeing more specialists from outside of cancer partnering with oncologists to manage some of the unique complications of molecularly targeted therapies.

What advice do you have for other clinicians who care for patients treated with these newer drugs?
Bhatti: It’s incredibly difficult to keep up with the potential toxicity profiles of all of these drugs. The best advice I can give is to be aware that these adverse effects can occur. The challenge we run into now is that because neuro-ophthalmic adverse effects are relatively uncommon, oncologists may not discuss them with patients when prescribing a new medication. Then, because many specialists like ophthalmologists are often not heavily involved in prescribing these newer oncology drugs, they may not be aware of potential toxicities, so they go unrecognized and untreated. That’s why it’s also really important for neuro-ophthalmologists to work closely with the patient and the prescribing oncologist to determine the best management strategy.

Now that these rare adverse effects are on my radar, I examine the medication list of every oncology patient I see to assess whether their therapy, rather than their disease, could be the source of any problems. Educating myself about these potential toxicities has really improved my clinical practice.