Moffitt Experts Discuss Innovation in Precision Medicine, Radiation Oncology, Value-Based Care

At a recent event held by The American Journal of Managed Care Institute for Value-Based Medicine titled, “Shaping the Future of Cancer Care: A New Era of Innovative Therapies,” oncologists discussed the current landscape and future of precision medicine, radiation therapy, cellular immunotherapy, and value-based perspectives in cancer care and medicine.

The event was held in partnership with Moffitt Cancer Center in Tampa, Florida. It featured physicians and staff from the center and was cochaired by Jason Bever, BLS, employer relations liaison, and Richard Kim, MD, service chief of medical gastrointestinal oncology and senior member in the Department of Gastrointestinal Oncology.

The opening session was presented by Tiago Biachi de Castria, MD, PhD, an associate member in the Department of Gastrointestinal Oncology, on advancing precision medicine developments in solid tumors. Precision medicine represents a paradigm shift in patient care, Biachi said, one that moves from treatment decisions based on anatomy to those focused on genetic alterations in tumors, including DNA, RNA, protein expression, metabolism, and microbiome analysis.

According to Biachi, precision medicine includes the following:

• Sequencing genes
• Locating cancer-causing genes
• Identifying ways to personalize treatment
• Finding ways to turn the immune system on
• Personalizing treatment with drugs that activate the immune system
• Discovering drugs that turn specific genes on or off

“If we can define precision oncology in 1 word, it is characterization,” Biachi said. “The reason why we need this is to deliver the right treatment to the right patient at the right time.”

Biachi illustrated the practical applications of precision oncology, such as choosing optimal treatments, predicting responses or resistance to therapies, and even determining chemotherapy doses based on specific genetic markers. He discussed different types of targets, including monoclonal antibodies that block ligand-induced signaling, small molecules that can inhibit receptor kinase domain activation, downstream signaling molecules that also can be inhibited by small molecules, and combination approaches involving antibodies and small molecules can be used.

Biachi described a success story in colorectal cancer involving anti-BRAF therapy, which highlighted the importance of understanding genetic mutations and mechanisms of resistance. The need to comprehend resistance mechanisms is emphasized for developing effective drug combinations and achieving better patient outcomes, he noted.

This was a phase 3 trial (NCT02928224) examining the combination of encorafenib (Braftovi), binimetinib (Mektovi), and cetuximab (Erbitux), and another arm of this study [using] encorafenib and cetuximab, Biachi said. “They compared these drugs with the standard chemotherapy for second-line treatment, and they proved that these targeted therapies could increase overall survival for those patients by 3 months with less toxicity compared [with] regular chemotherapy.”

Looking toward the future, Biachi discussed challenges, including the high cost of implementing precision oncology technologies. Strategies to reduce costs involve smarter clinical trial designs, utilizing preclinical models, and improving drug development efficiency. Biachi envisioned a future where advanced technologies, beyond current next-generation sequencing panels, are translated to clinical practice, analyzing various aspects such as the tumor microenvironment and microbiome.

When asked in an interview about key findings from his presentation, Biachi relayed the importance of population-based model and reducing cost. “We can bring more patients to be treated in clinical trials, and maybe expedite this drug development,” he said. “Because we do know that drug development is a critical component of health care costs.”

Collaborative models for clinical trials can expedite patient recruitment and enhance the success rate of drug development, he noted. “The future is this next step of not only identifying genetic alterations in the tumor but also assessing tumor microenvironment, microbiome, not only gene expression but RNA expression and protein expression,” Biachi said. “And again, I would say [we need] more innovative models for clinical trials, not site-based, but maybe a population-based clinical trial. And for this, of course, precision oncology is critical.”

Innovation in Radiation Oncology
Jessica M. Frakes, MD, associate member in the Department of Radiation Oncology, opened a presentation on innovation in radiation oncology by discussing its history as a pillar of cancer treatment. Unlike surgery, radiation therapy is largely noninvasive and requires means other than a physician’s vision to guide the radiation beam, Frakes said.

She emphasized the importance of technology in radiation oncology. “From a radiation oncology perspective, if you can see it, you can treat it, and if you can treat it, you can potentially cure that tumor,” she said.
Frakes explored advancements in radiation technology, particularly the transition from CT-guided radiation to MRI-guided radiation.

The benefits of MRI-guided radiation, she said, include as follows:

• Exceptional soft tissue contrast
• Continuous infraction imaging
• Gross tumor volume that is directly visualized, with its position gating the beam
• Routine online adaptive replanning

Frakes then explained the benefits of implementing MRI-guided imaging into a virtual reality clinic setting, which was found to improve the patient experience with treatment, allowing patients who initially could not tolerate treatment to complete treatment and helping reduce their anxiety.

“As the technology has improved and there are smaller spaces for patients to be in, it brings about a lot of anxiety, a lot of issues with claustrophobic patients and various other factors,” Frakes said. “And so, one of the nice things that we’ve done from a patient perspective is bringing virtual reality into the clinic.”

The presentation also delved into the realm of adaptive therapy, discussing both CT-guided and MRI-guided approaches. Frakes emphasized the potential of adaptive therapy to personalize treatment by adjusting radiation doses based on day-to-day variations in tumor and normal tissue positions. Proton therapy was highlighted as a valuable tool, especially in scenarios where minimizing radiation to surrounding healthy tissues is crucial, according to Frakes. She touched on the evolving landscape of combination therapies, incorporating radiation with systemic treatments such as targeted therapy and cellular therapy.

She also discussed emerging areas of research in radiopharmaceuticals. “There is new technology [that is] using radiopharmaceuticals to determine where to treat patients,” Frakes said. “No trials have been started. This is really just in the infancy, but I just wanted to put up there that this is the direction things are going [toward] personalizing treatment.”

Frakes concluded her presentation by highlighting advances in personalized therapy based on genomic signatures, mathematical modeling, and radiomic- derived doses. “Radiation really shouldn’t be a one-size-fits-all approach,” Frakes said. “We have a lot of tools to delineate what dose we should be giving patients, and [we are] starting to follow our medical oncology colleagues by really looking at the genomic profile and other factors to delineate what tool we should be using for each patient.”

Updates in Cellular Immunotherapy
Dae Won Kim, MD, a gastrointestinal oncologist at the center, discussed the use of cellular immunotherapy for solid tumors, highlighting tumor-infiltrating lymphocytes, chimeric antigen receptor T-cell therapy, T-cell receptor therapy, and bispecific T-cell engager therapy.

“Since the discoveries of immune checkpoint molecule CTLA-4 and PD-1, cancer immunotherapy has become one of the major therapeutic options, in addition to surgery, radiation, and chemotherapy,” Kim said.
Kim explained the importance of tumor antigens in immunotherapy and addressed the challenges and successes of each approach.

• Tumor antigens, Kim said, include as follows:
• Intracellular or extracellular tumor-specific molecules
• Oncofetal antigens, such as carcinoembryonic antigen
• Oncoviral antigens, such as human papillomavirus E6 and E7
• Overexpressed antigens, notably HER2
• Cancer/testis antigens, including New York esophageal squamous cell carcinoma
• Mutated antigens, notably KRAS, TP53, BRCA

Kim said that the ideal tumor antigen for immunotherapy includes overexpression on cancer cell surfaces and no or very low expression in normal tissues. Additionally, Kim noted how clinical trial data are shared to showcase the efficacy of these therapies in various types of cancers. Furthermore, he emphasized the promise of cellular immunotherapy in treating patients with solid tumors, while acknowledging the need for further refinement in terms of efficacy and toxicity management.

Although some studies of cellular immunotherapy show promising results in solid cancer, “Improvement in efficacy and toxicity is needed to go to the next level,” Kim said.

Pursuing Value-based Care
The evening ended with a discussion among Asmita Mishra, MD, MBA, associate member in the Department of Blood and Marrow Transplantation and Cellular Immunotherapy; Donn W. Davis, PharmD, MHA, BCPS, pharmacy operations manager; and Joseph Mirrow, director of managed care.

The panelists discussed challenges and strategies related to the implementation of value-based medicine in cancer care; adoption of new therapies; integration of technology, such as artificial intelligence into decision-making; cost considerations; adherence to guidelines; patient engagement; and the challenges health care organizations face in transitioning to value-based models.

“We’re really making inroads in integrating data and technology, sharing data with payers, sharing data with other institutions,” Mirrow said.
The panelists also emphasized the importance of data interoperability, collaboration, and continuous improvement in achieving high-quality outcomes while controlling costs.

“Hospitals were, for a long time, really good at one thing: billing,” Mirrow said. “And now you need to be interoperable with a whole care continuum and care interoperability team; you need to build in cultural and workflow changes; and at the far end of the spectrum, of course, is taking a lot of financial risk.”

Regarding the main factors contributing to cost, Davis noted the role biosimilars play as an alternative for controlling costs.

“We were very much a forerunner in [biosimilars] and in that space,” Davis said. He added, “The whole spirit of the Biosimilar Act’s approval was to lower that cost to the patients.” Formally known as the Biologics Price Competition and Innovation Act, this 2010 legislation was included in the Affordable Care Act.

“We got ahead of that very early on [for] our patient models and quickly implemented it housewide, depending on the disease state…. So the adoption of that has been very helpful, and it’s helped [increase] access of care to our patients, and other payers have been appreciative…and working with them,” he said.

The speakers collectively emphasized the pivotal role of patient engagement. Informed and engaged patients are generally more adherent, and they are actively involved in decision-making processes.

“An informed and engaged patient is the most [adherent] patient. If you have a patient who is part of the decision-making process, that is the patient who is going to have not necessarily the best outcome in terms of survival, but the best quality of life along the way,” Mishra said.

One attendee asked the panel which elements of patient engagement in clinical trials are most important post COVID-19 compared with before the pandemic.

“COVID-19 made it extremely apparent that people who didn’t have access to health care had poor outcomes, and we certainly see that in the cancer space,” Mishra said. “People with disparities do not have as much genomic testing, do not get targeted therapies as frequently as those people who have better access to cancer care, and certainly [do not get into] clinical trials.”

When asked what the level of knowledge was for medical directors or staff of payers with regards to new therapies that have been launched, Mishra stated frankly that the level of knowledge among payers and even among those in the oncology space is very low.

“I think this is where I feel that it has been a really amazing role for me to live in that space, treat those patients, and then additionally be in the payer strategy role,” Mishra said. “Because you’re right, my job has been a lot of education. It has been really an amazing time for that because as these drugs get approved at a rapid-fire pace, a lot of that has been trying to explain what those drugs are. And then, quite frankly, [we have to explain] the toxicities and why it’s so important for the patients to receive [the drugs], all the monitoring that goes along with them, and why people need these extremely expensive drugs.”