David Alsadius, MD, PhD, Senior Medical Director, Oncology Center of Excellence, IQVIA
Sergio Sánchez-Gambetta Director, Design Analytics, IQVIA
Matt Simmons Senior Director, Oncology Strategy, IQVIA Biotech
Investment into cancer drugs is reportedly expected to reach $375 billion by 2027, making it evident that all eyes are on the accelerated discovery, development, and delivery of novel and effective therapies to improve patient outcomes. And rightfully so, because patients worldwide need treatment options that reduce disease burden, delay progression, and prolong survival while improving or maintaining quality of life.
Despite significant therapeutic advances in several tumor types, there is still a high unmet need in cancer care, especially for rare or difficult-to-treat cancers. There is a sense of urgency and strengthened commitment among the global oncology community to elevate innovation in all aspects of drug development. This includes how to address the complexities that come with the high level of transformative science.
Ahead, we discuss several exciting areas of progress in oncology R&D and what sponsors, contract research organizations (CROs), regulators, and other key stakeholders will need to keep in mind for successful drug development.
Exploring emerging modalities: Radioligand therapeutics
Radiopharmaceuticals have been instrumental in diagnostic imaging procedures for many therapeutic areas for years. They have also been an important tool for treating certain cancer types, with sodium iodine-131 being the first radiopharmaceutical approved by the FDA in 1951 for the treatment of thyroid disorders. Together with several other isotopes, iodine-131 is now being used to develop novel radioligand therapeutics (RLTs), proving that scientific breakthroughs in cancer R&D do not always have to focus on newly discovered compounds alone.
RLTs are quickly grabbing the attention of cancer-care stakeholders and creating excitement about their targeted modality, which allows delivery of radioactive agents directly to cancer cells and/or the tumor microenvironment. After showing clinical benefits for the treatment of advanced prostate cancer and neuroendocrine tumors, RLTs are being evaluated across multiple tumor types (e.g., breast and lung) and blood cancers.
Innovation meets intricacies in RLT development
As large pharmaceutical companies invest billions into evaluating the promise of RLTs, it is important for all stakeholders to build and sustain a detailed framework to support their efficient development across the patient’s full cancer-care journey, from diagnosis to treatment administration, and across countries. Integrating these agents into clinical evaluation and use requires specialized knowledge to protect both patients and providers, as well as adherence to regulators’ best practices for clinical trial design.
- In early trial planning, sponsors will need to consider several nuances to optimize RLT development and ensure equitable access to patients in need:
- Diagnostic capacity. Access to diagnostic tools (e.g., PET and SPECT scans) needed to identify patients suitable for treatment with RLTs may vary per location. Selecting sites with up-to-date imaging equipment that can efficiently optimize diagnostic visits and treatment schedules with patient preferences in mind is critical.
- Patient referral processes. Given the intricacies of RLT diagnosis and treatment, clear referral pathways and collaboration between sites and providers can help maximize patient flow from end-to-end. However, there are currently no standard referral pathways for RLTs across sites and countries. A recent analysis among European countries says that in France the estimated diagnosis-to-treatment time is three weeks, while in Germany and Spain, it is closer to seven to eight weeks.
- Differing regulatory frameworks. Sponsors need to carefully evaluate country and regional regulations for RLT development. RLTs are not thoroughly addressed in many cancer policies. Even in international guidance, there are significant discrepancies regarding radioprotection among countries. Additionally, regulations may not address the differences between radioisotopes (e.g., diagnostic or therapeutic), which may restrict use of some RLTs in some regions. As regulators aim to better standardize RLT integration into country-specific and local treatment approaches, sponsors will need to closely monitor updates in applicable requirements and guidance.
- Skilled trial sites and experienced workforce. RLT administration is typically an in-patient procedure with hospitalization times varying per isotope and country regulations, so sponsors need to account for which sites have enough beds for isolation requirements. In early planning, it is also key to confirm these sites are staffed with expert nuclear medicine physicians, especially for global trials. Ensuring sites are appropriately trained on imaging, treatment calibration, and dosimetry is also necessary. If aiming to conduct RLT trials in Europe, for example, per a recent report, sites in Germany have 8.9 of these expert physicians per center of interest compared to Italy (6.3), Spain (6.6), and France (2.9).
- Robust supply chain system. RLT supply chain strategies need great attention to detail at every step. From scalable production to careful transportation and quality control, sponsors have to adhere to strict regulatory requirements and the International Atomic Energy Agency’s international quality assurance standards to ensure the safe handling of these materials. When developing new RLTs, it will be critical to work closely with regulators to uphold quality control throughout the supply chain.
As the collection of data demonstrating the value of RLTs grows, sponsors developing these therapies will be able to further fine-tune approaches and gauge what is needed to update policies and optimize trial design.
Moving beyond discussions, creating actionable change
Are the industry’s collective oncology R&D efforts providing patients with optimal care and treatment plans, and if not, what are some practical ways to transform current approaches to achieve better outcomes? As global oncology R&D continues to bring forward some of the most compelling novel science in droves, these questions are top of mind for regulators, drug developers, CROs, etc.
There is a noticeable push from regulators and public health groups for innovative cancer care approaches that put patients front and center, accounting for their quality-of-life needs, perspectives, and treatment challenges in a tangible way.
For example, the FDA’s Oncology Center of Excellence currently has more than 30 ongoing initiatives to improve patient centricity in oncology drug development. This includes its patient-focused drug development program, which aims to help stakeholders incorporate patient experience data into R&D and regulatory decisions. Also, the FDA’s Project Endpoint is designed to further explore potential uses for early, novel endpoints that may help improve patient outcomes, such as minimal residual disease in solid tumors via liquid biopsies.
The industry mindset is shifting from developing drugs for patients to with patients, keeping empathy in mind. For one, in terms of practical barriers to optimal care, not being able to see a provider quickly after a new diagnosis of cancer can be a frustrating and concerning time for patients. According to a paper published in the Journal of Clinical Oncology Practice earlier this year, studies show that “delays in cancer care are associated with inferior cure rates and survival across all disease sites.” To address the issue of lengthy wait times from diagnosis to treatment and backlogs of scheduling appointments and related workflows, industry experts are examining the option of same-day treatment visits after diagnosis.
When shifting away from a “first-come, first-served” policy, providers implementing same-day visits would need to consider how they’ll rework busy daily schedules to accommodate more time with patients and what to do when seeing patients who did not receive thorough diagnostic evaluations. A standardized care path detailing patient visit flow and expected timelines from disease presentation to imaging and treatment decisions may be effective.
The industry is also moving beyond discussing the potential benefits of early and broader genetic testing to further personalize treatment approaches. For example, the UK National Health Service’s 100,000 Genomes Project aims to sequence 100,000 whole human genomes from patients with common cancers and those with rare diseases and review existing clinical insights to better understand disease causes and fine-tune diagnosis efforts and treatment plans. Through projects such as this, industry stakeholders can leverage data-driven analytics directly from patients to extract and share patterns of interest to improve patient responses and further personalize drug development approaches and potentially provide earlier interventions.
Understanding the real-world patient journey
Traditional data sources, such as medical guidelines and journals, are rigid by nature, manifest momentary realities, can often be incomplete and do not always adequately account for regional differences in prevalence of oncology subpopulations. This includes missing disease classifications and lack of detailed biomarker data. Gaps in granular data lead to the use of assumptions or proxies. This can compromise trial design by leading to inaccurate patient estimations, which hurt recruitment efforts and cause costly amendments.
Like never before, the use of applied analytics and artificial intelligence/machine learning gives trial sponsors a tremendous opportunity to leverage up to a billion unique non-identified patient records from claims data, medical records, and other real-world data (RWD) sources to gain a stronger understanding of patient journeys within specific types of cancer. By understanding treatment pathways and the number of patients within them, sponsors can make data-informed decisions about their eligibility criteria selection and/or its parameters. These insights are invaluable for optimizing trial design because they provide more precise estimations of specific subpopulations of patients with cancer, which accelerates identification and engagement of participants, one of the biggest challenges to successful completion of oncology trials.
Through RWD synthesis and analysis, there is opportunity to dive deeper into individual patient-population journeys with practicality that can help in several key areas:
- Within a given indication, sponsors can evaluate relevant treatment patterns to improve study design. For example, for women being treated for ovarian cancer, gauging who has received first, second, third, fourth, or even fifth lines of treatment is helpful for understanding their real-world journeys instead of relying only on published medical guidelines, which may not follow their actual treatment pathways.
- To gauge trial feasibility, sponsors can identify whether there is an adequate number of patients currently on a treatment journey that aligns with a specific trial protocol. RWD can reveal how modifying eligibility criteria can impact patient prevalence, thus informing recruitment potential.
- RWD can provide insights into outcomes of interest based on what is typically seen in standard of care to support endpoint selection. For example, if only 12% of a patient population was hospitalized within the last 15 months, then hospitalization would not be a proper endpoint for a 15-month study.
- Regarding site identification, sponsors can see where patients are located and receiving treatment and pinpoint specific institutions prescribing treatments that may align with the trial protocol.
- Detailed biomarker data can inform country and site strategies by identifying patients with positive results, which may lead to faster recruitment rates.
Furthermore, applying RWD linked to ethnicity data allows exploration of available eligible patients by race and ethnicity. RWD can also help identify how different race and ethnic groups respond to various lines of treatment and how changes in eligibility criteria can impact willingness to participate and availability. Uncovering these nuances can help sponsors understand the impact their study-design decisions have across various populations, enabling them to better define FDA-required diversity goals and to inform engagement and recruitment efforts.
Tangible steps
Though there is still much to be done, the industry is diligently working to explore practical ways to match the potential of scientific innovation and increased collection of real-world lessons to improve patients’ health journeys. Whether effectively providing earlier interventions, widening underrepresented communities’ access to novel therapies, transforming clinical research to bring quality drugs to market quicker, or making other advances, the oncology community is constantly in exploration mode, aiming to create actionable change that patients need to see.
David Alsadius, MD, PhD, Senior Medical Director, Oncology Center of Excellence, IQVIA; Sergio Sánchez-Gambetta, Director, Design Analytics, IQVIA; Matt Simmons, Senior Director, Oncology Strategy, IQVIA Biotech
