Targeted agents and immunotherapies are two of the most promising areas for significant advancements in cancer treatment. Envision Pharma’s scientific solutions division lead Rebecca Goldstein, discusses this topic and other developments that cancer patients and their loved ones should be paying attention to.
People with cancer and their caregivers have long been active participants in discussions of how they are treated, but in the current digital information age, it is becoming more common for patients to self-advocate for the latest advancements in therapy. With so many active research areas in oncology, patients and their loved ones can easily be overwhelmed by information and not know where to direct their attention.
According to Envision Pharma’s Rebecca Goldstein, the developments in cancer treatment for patients to watch are those that build upon the two most revolutionary treatment advances we already have: targeted agents and immunotherapy. Oncogenic driver mutations are being found more quickly and targeted more effectively through new technology, and the first wave of immunotherapies are being improved upon by combining them either with other immunotherapies or with the standard of care.
Cancer patients and their loved ones can easily get overwhelmed by the sheer number of choices available. As Rebecca Goldstein says, “The fact is we have a lot of really active drugs in cancer right now. We have drugs that work really well, we have drugs that can cure cancer, we have surgeries that can cure cancer.”
Unfortunately, these treatments don’t work for everyone. Not all patients will benefit from any given drug, and some of those who do benefit will not benefit long-term. Some patients will experience a remission for a time, until the cancer succeeds in finding a way to begin to grow again. When that happens, the cancer comes back, and the patient needs another option – until there are no more options.
Other patients don’t benefit from the established standard of care because they can’t tolerate the drugs that we’ve got. The drug itself is too toxic for them, or they have some health condition that disqualifies them from receiving that drug.
According to Goldstein, “When patients or families are trying to learn about the latest advances in cancer treatment and ask me where to focus, I say I would be looking specifically for new advancements that will help me in one of these areas: Do I have a chance to live longer? Can I keep my cancer in check for longer? Can I be spared from certain side effects or just improve the quality of the time that I have left?”
Major improvements in oncogenic targeting have fallen into two approaches: finding the targets in patients more quickly and easily and improving the technology by which we target the mutations.
The most relevant innovation is already here: instead of looking for oncogenic drivers individually, we can put them in panels. Ongoing improvements in multi-gene panels are gradually lowering the price of these tests and making them accessible to more patients.
Innovative therapies that are making oncogenic targeting better are using different novel technologies to more thoroughly target a particular pathway, such as bi-specific antibodies; or those that use the mutation as a delivery mechanism for another stronger drug, such as antibody-drug conjugates.
Antibody drug conjugates have recently experienced major leaps forward in terms of design elements. “There are a lot of different design elements for antibody drug conjugates that can impact how well the actual molecule works in patients,” explains Goldstein. “The way that the chemotherapy is linked to the antibody, the type of chemotherapy that you choose, there are all sorts of design elements that you can play with.”
We’ve recently seen the first positive phase III study that put two ADCs developed against the same target head-to-head in the DESTINY 03 trial: proof that relatively small differences in drug design can have a significant impact on what happens to patients.
Possibly the most notable advancement in immunotherapy was with immune checkpoint inhibitors, which work by turning the patient’s immune system back on after the cancer has turned it off in order to “hide.” However, dramatic increases in lifespan don’t happen for most patients. We are continuing to get better and better at knowing how to extend the life-extending benefits of immune checkpoint inhibitors to more and more and more patients by pairing them with other drugs that work directly against the tumour.
“First and foremost, if you combine immunotherapy with the standard of care, you can sometimes extend the benefits of immunotherapy because you’re providing an extra level of efficacy to help get over the hump,” says Goldstein. “For instance, when you combine immunotherapy with chemotherapy, in some tumour types, you get the benefit of rapid tumour control from the chemo, but then you have the immunotherapy that can encourage the immune system to respond to the cancer. You’ll get that long-term benefit from an immune system that continues to survey the patient’s system and eliminate any residual cancer.”
Because immunotherapy targets the patient’s immune system, you can also combine two different immunotherapies to target multiple parts of the immune system. For any individual patient, this combination strategy improves the chances that the treatment is targeting the correct part of the immune system that their cancer is using to hide.
According to Goldstein, “That’s exciting because the immune system is very, very complex. That means there are lots of different ways that any individual cancer may be using to hide, also lots of different ways that you can intervene with a drug. Sometimes, if your cancer is not responding to one immunotherapy, it’s because that particular therapy is targeting part of the immune system that the cancer isn’t necessarily leveraging. You might need a different immunotherapy, or you might need to put two of them in combination.”
Clearly, we need to get better at matching individual therapies to individual patients based on what their own anti-cancer immune responses look like. There are some, but not many, tests that can be done to see how a patient’s own cancer may be hiding from their immune system. Patients should never shy away from asking their health care team about the latest advancements and technology in cancer testing.
As more and more patients become eligible for novel targeted therapy and immunotherapy and new treatments are used earlier in the course of cancer, it’s increasingly important to balance incremental improvements in care with health system impacts to ensure every patient has the same access to the best care. Yet, as Goldstein points out, the question of how to achieve this balance is still unanswered.
The gold-standard question in oncology is, “Do patients live longer if they get this treatment versus if they don’t?” but with advancements in cancer treatment, more and more patients now get multiple lines of therapy in sequence. It then becomes harder to tell what impact each treatment has on a patient’s overall lifespan.
To truly define the impact of a new therapy, Goldstein suggests additional questions that look to what patients’ priorities are: not just to live longer, but to live cancer-free for longer—to have more time when the impact of the disease does not burden them.
As Goldstein says, “Can you functionally cure more patients? Can you keep disease from coming back, which makes it much harder to cure every time it happens? Can you improve the quality of the days that each patient has, not just physically but mentally and emotionally?” The answers to these questions will demonstrate the true value of any therapeutic advancement.
Rebecca Goldstein currently serves as a scientific solutions division lead at Envision Pharma. A PhD-trained cell biologist and immunologist, Rebecca has held many roles over the years, supporting oncology and immuno-oncology development teams as a researcher and in strategic scientific communications. She lives in central New Jersey in a full house with her husband, three children, extended family, and two Siberian huskies.
Founded in 2001, Envision Pharma Group is a global, innovative technology and scientific communications company serving pharmaceutical, biotechnology, and medical device companies. Envision is a leading provider of evidence-based communication services and industry-leading technology solutions (iEnvision) that have applicability across many areas of medical affairs and related functional responsibility. Envision Pharma Group provides services and technology solutions to more than 90 companies, including all of the top 20 pharmaceutical companies.
Envision has 20 offices: six in the United Kingdom – Bishop’s Stortford, Glasgow, Horsham, London, Wilmslow, and Alderley Edge; one in Serbia – Subotica; one in Hungary – Szeged; one in Coimbra, Portugal, nine in the United States – Fairfield and Glastonbury, CT, Philadelphia and Wyomissing, PA, Warren, NJ, Boston and Melrose, MA, Powell, OH, Pasadena, CA; and two in the Asia-Pacific region – Tokyo and Sydney. The company employs 1100+ team members, including over 250 highly qualified and experienced in-house medical writers, and 200 technology solutions team members who provide software development and customer support. To find out more, visit www.envisionpharmagroup.com.