Authors: T.J. Sharpe
Immunotherapy is the hot topic of oncology research in the last few years. As this timeline of immunotherapy highlights, discoveries and treatments dotted the landscape sporadically until early this decade, when the anti-CTLA-4 antibody ipilimumab (Yervoy®) kick-started a wave of immunotherapy innovations. The latest approvals show that existing immunotherapy drugs are effective on a number of traditional cancer types. Further, combination therapies continue to show promise and other novel checkpoint inhibitors lead the field into an ever-increasing number of possible treatments.
“Digging a little deeper, though, the true value of this research becomes evident…”
Recently, an extremely high response rate for a specific kind of melanoma highlighted how far immunotherapy has come. Researchers at Moffitt Cancer Center (FL, USA) demonstrated that desmoplastic melanoma patients’ response to anti-PD-1 or anti-PD-L1 antibodies was significantly higher than patients with more common forms of melanoma. As a melanoma patient – and one who was treated at Moffitt – hearing this news gave an initial “That’s great!” reaction that has become commonplace when reading new anti-PD-1 antibody results. Digging a little deeper, though, the true value of this research becomes evident.
The significance of the work wasn’t the results it gave to a very, very small subset of patients. While that is great news for them, it’s not much to move the needle for other treatments on its own. What will make that needle move is the resulting work done to determine the underlying mechanisms. The findings led Moffitt to collaborate with other cancer centers to perform whole-exome sequencing of the melanoma tumors. This, in turn, led the team to discover that contrary to existing belief, desmoplastic melanomas had a high mutation load with very specific mutations.
THESE findings are the real breakthrough; that this specific cancer type, previously theorized to be unaffected by immunotherapies due to its structure and lack of mutations, actually had characteristics that made it a target for a specific immunotherapy – one that was also proven to work. It continues the progress the hypothesis that cancer can be treated via genetics versus tumor origin. With Keytruda® (pembrolizumab) already granted a regulatory approval based on tumor genetic markers, that hypothesis is already being proven.
When cancer centers share findings, data, theories and tests, it’s more than just smart people talking shop with other smart people. Breakthroughs happen when labs begin comparing notes; when researchers see non-familiar treatments as complimentary, not threatening or inferior; when pharmaceutical companies view other pharmaceutical companies as potential partners instead of rivals. That a major United States cancer center engaged their colleagues (even ones they may be competing with for patients) and pushes to find out WHY something good just happened, everyone reaps the benefits – the researchers, the treating physicians, the pharma companies… and, crucially, the patients at the end of all of this.
“Breakthroughs happen when labs begin comparing notes; when researchers see non-familiar treatments as complimentary, not threatening or inferior; when pharmaceutical companies view other pharmaceutical companies as potential partners instead of rivals.”
The overarching thing these results bring? Hope. This is evidence that these new breakthrough therapies can work on even the most stubborn of cancers, if only the cancer and the treatments are correctly identified and paired. Now, there’s another layer of treatment possibilities brought on by the genetics of a cancer, and with it, more potential treatments and combinations. If a cancer doesn’t respond to the standard of care for its origin, well, maybe it will to a treatment that has shown promise against its genetic features.
The only way to validate this hope is the continued accrual of data via trial. For researchers, this means advocating for trials that push targeted data collection for multiple purposes. Research that doesn’t simply look for a way to make a small population live incrementally longer than they do on an existing therapy. Research that builds upon the knowledge already validated to support the theories being shared and the collaborations looking to prove treatment worth across multiple pathways. This research has value far downstream, as that knowledge base is built for the next wave of treatments and the scientists working on them.
Patients also need to be shown the value of their participation in this effort. Oncology trial participation rates continue to remain low, despite efforts to promote their awareness and participation. However, the early KEYNOTE and CheckMate melanoma studies, for pembrolizumab and nivolumab, respectfully, had opposite issues – they filled up so quickly that in some cases, patients were left without the chance to try these new therapies as compassionate use struggled to keep up with leftover demand from filled trials.
Patients understood the value these drugs brought to their healthcare; ultimately, an untold number of cancer patients got a treatment that would have been otherwise unavailable. As patients consider the “what’s in it for me?” part of trial consideration, educating them on the greater good that goes along with the immediate benefit is a chance every oncologist has to add meaningful data to the body of knowledge future patients, and their oncologists, will use to determine the right treatment at the right time for the right cancer. That is how to use the model laid out by the Moffitt team to accelerate the research for a better treatment and, ultimately, a cure for the right patient.
T.J. Sharpe is a Stage IV melanoma patient who shares his journey through cancer in the Patient #1 Blog on www.oncology-central.com, www.philly.com/patient1/, www.SkinCancer.net, and on www.NovartisOncology.com. He was diagnosed in August 2012 with melanoma tumors in multiple organs, only 4 weeks after his second child was born. Since then, he has undergone six surgeries and four immunotherapy treatments over two different clinical trials. The initial failures, and subsequent complete response, have been chronicled in his blog posts since December 2012. In addition to writing, he is a keynote speaker and consultant to the biopharma and clinical research industries, bringing an educated patient voice as a true stakeholder in challenging healthcare’s status and making a difference in patients’ lives via his company, Starfish Harbor LLC. A South Jersey native, T.J. lives in Fort Lauderdale, FL, with his wife Jennifer and two young children, Josie and Tommy.