What oncology market researchers should understand about toxicity

On July 17, the FDA’s Oncology Drugs Advisory Committee (ODAC) recommended against approving the antibody-drug conjugate Blenrep (belantamab vedotin) for the treatment of multiple myeloma (https://www.fiercepharma.com/pharma/fda-advisors-spurn-gsks-blenrep-comeback-dreams-safety-trial-concerns). Blenrep had previously been removed from the market as a single agent after a confirmatory study required as part of the expedited approval failed to show benefit.  More recent studies (DREAMM-7 and DREAMM-8) had shown a substantial benefit in efficacy in combination with standard myeloma therapies such as Velcade (bortezomib) or Pomalyst (pomalidomide), but ODAC raised concerns about high rates of dose modification in the DREAMM-7 and -8 trials, the low rates of US patient enrollment in those trials, and the frequency and degree of ocular toxicity.

The FDA has since delayed its decision date for Blenrep (https://www.fiercepharma.com/pharma/fda-pushes-back-blenrep-decision-date-putting-gsks-multiple-myeloma-comeback-dreams-ice).  In the interim, Health Canada has approved it.  Even if it is eventually approved in the US, hematologist/oncologists, especially those in the community, are likely to weigh the benefits and risks of these combinations carefully, particularly given the rates of ocular toxicities.

Oncologists are used to managing toxicities.  In the interviews I have conducted with oncologists over the years, I have spent a lot of time asking about, and learning about, the toxicities of different oncology medications.  I have learned that oncologists tend to care about three aspects of toxicities:

• Are they manageable? That is, can toxicities resolve when patients are treated with supportive care medications or dose adjustments?  Do patients need to discontinue therapy for these toxicities?
• Are they predictable? That is, do oncologists know what to expect when the toxicity occurs?
• Do they affect patient quality of life? Oncologists often refer to some toxicities, particularly cytopenias, as “paper toxicities” because the patient doesn’t feel worse.  In contrast, nausea and fatigue are not necessarily life-threatening but can have a significant impact on QOL.

By these standards, ocular toxicity poses a challenge.  Oncologists are unfamiliar with managing ocular toxicity, making it both challenging to manage and difficult to predict, and it can certainly affect patient quality of life when it occurs.  They will need to involve ophthalmologists in the care of their patients, and they do not necessarily have long-standing relationships with ophthalmologists, nor do patients always have their own ophthalmologists.  In clinical practice, could this be too much of a barrier for physicians and patients, particularly given that Blenrep regimens, while efficacious, are not curative?

When toxicity poses a challenge for adoption, it is incumbent upon manufacturers to make oncologists’ jobs as easy as possible.  In this case (and in the case of other antibody-drug conjugates that cause ocular toxicity), enabling oncologists and their patients to find ophthalmologists who are willing and able to carry out monitoring for ocular toxicity (and treatment, when required) could go a long way to overcome this potential barrier.  Guidance regarding how to manage these toxicities, and/or partnership with experts with experience in managing the toxicities, can also be crucial to ensuring physicians’ comfort with a new therapy or regimen and, eventually, uptake.

A final crucial issue for marketers is to understand how oncologists talk to their patients about these toxicities.  Oncologists may be persuaded of the benefit of a regimen and may be comfortable managing toxicities by themselves or in collaboration with other specialists, but they still need to ensure that patients are comfortable with the risks and benefits of a given treatment and know what they need to do if a toxicity occurs.  Oncologists often mention to us that messaging is important not just for their understanding of a given medication, but it can also provide vocabulary or a framework for them to educate their patients in turn.