Gaining real-world oncology insights from engagement of key opinion leaders through virtual and live solutions

Evolution in cancer therapeutics offers vast opportunities to learn from key opinion leaders

Traditional approaches for cancer treatment have included surgery, radiotherapy, and chemotherapy. In recent decades, however, an intensifying body of knowledge surrounding the role of genomics and the immune system in cancer has led to the development of therapies targeted to specific molecular alterations and/or other biologic characteristics (eg, immune suppression). As such, molecularly personalized therapy, or precision therapeutics, in which an individual’s characteristics and/or genetic profile is used to guide clinical decision making, has emerged as the fundamental method to treating patients with cancer. This approach is aimed at selecting the right treatment for the right patient at the right time. 

Along with advances in genomics, an exponential growth in data mining capabilities has also led to a major shift away from the traditional tumor type-centered approach toward a gene-directed, histology-agnostic treatment approach. This paradigm shift is reflected by the emergence of precision medicine trials with innovative study designs, such as basket trials that target a common genetic defect across many histologies and umbrella trials that involve a single histology and evaluate different treatments based on genomic alterations in specific patient subgroups. 

Furthermore, immunotherapy has emerged as a principle therapeutic strategy to treat cancer via stimulation of the body’s own immune system to kill cancer cells. In fact, cancer immunotherapy was named as 2013’s Breakthrough of the Year by Science Magazine and has revolutionized the field of deoxyribonucleic acid (DNA)  therapeutics. Several innovative immunotherapy approaches, such as checkpoint blockade, cell-based products, vaccine platforms, oncolytic viruses, modified cytokines, CD3-bispecific antibodies, and adoptive cell therapy, have already been approved and continue to be investigated. 

Additionally, the discovery and approval of autologous, patient-specific chimeric antigen receptor (CAR) T-cell therapy represents the result of efforts to use DNA plasmids or vector technology to tip the balance in favor of the immune system for the elimination of hematologic malignancies. Efforts are underway to expand CAR T-cell therapy’s applicability to solid tumors and also to overcome the patient-specific hurdles of such CAR T-cell platform and the time required for manufacturing via universal “off-the-shell,” or allogeneic, CAR-T cell alternatives.

Lastly, while conventional DNA therapeutics have relied on finding small molecule drugs and developing recombinant proteins to target active sites and subsequently inhibit their function, ribonucleic acid (RNA) therapeutics have emerged as the latest advancement to drug development for rare genetic disorders, including cancer. RNA therapeutics are the category of drugs that target highly specific pathways in sites previously considered “undruggable.” RNA therapeutics also take less time to develop compared with their DNA counterparts as their manufacturing processes are relatively simple and are anticipated to be more cost-effective. Together, these advantages of RNA therapeutics are projected to propel personalized medicine to new heights, particularly following the record time to market of COVID vaccines using messenger RNA and also historical approvals of various RNA interference drugs. RNA therapeutics currently available or under investigation include antisense oligonucleotides, aptamers, small interfering RNAs, microRNAs, and messenger RNA.

Gaining provider and payer insights via virtual and live engagements

Provider insights, including from specialized clinicians in oncology and rare diseases, are important to ensuring appropriate formulary or health technology assessment (HTA) positioning and uptake of innovative products to help bridge the gap between the “what” and the “why” behind growing therapy choices and patient-centered management. Based on the impact of the COVID-19 global pandemic, obtaining these insights has become challenging and has highlighted the need to use virtual environments, which offer a flexible option that can be tailored toward the manufacturers and their particular therapeutic area and/or situation. A publication by Hackshaw et al described the use of a web-based study to collect and evaluate provider preferences for treatment of hypothetical metastatic renal cell carcinoma patients set the precedent for collecting provider insights in a virtual environment. By utilizing a virtual platform, researchers were able to gain insight from a variety of practitioners into varying clinical scenarios to help discern preference and perception of treatments in a complicated and crowded disease space. Additionally, payer insights can provide relevant and actionable information to help overcome market access challenges. Virtual or live engagements offer the opportunity to bring together a broad mix of payers from national and regional plans as well as formulary and HTA decision makers to receive actionable qualitative and quantitative insights related to market access, clinical, and data generation needs for investigational drugs in development and/or approved therapies in cancer and rare diseases.

Provider and payer insights aid in overcoming oncology market access hurdles

In general, a collection of provider and/or payer insights may aid in overcoming 5 potential hurdles: 1) therapy-related—perception of toxicity profile or interpretation of efficacy data (eg, sequencing of agents in the crowded space like renal cell carcinoma or chronic lymphocytic leukemia), 2) patient-related—awareness of supportive care or access programs (eg, securing multi-tumor access to drug and testing across a range of indications) or worry regarding adherence/compliance tools (eg, oral targeted therapies), 3) knowledge-based—comprised understanding of the patient population/sub-populations (eg, complexity of high-risk myelodysplastic syndromes) or low familiarity with an evolving standard of care (eg, non-metastatic castration-resistant prostate cancer or heavily pretreated relapsed/refractory population like multiple myeloma), 4) infrastructure-based—absence of supporting resources or lack of internal procedural pathways (eg, Risk Evaluation and Mitigation Strategy (REMs) program, specialty pharmacy), and 5) cost-based—incomplete understanding of direct and indirect cost drivers of therapy, negative impact of high one-time payments, and, importantly, a growing need for demonstrating the value of therapeutic innovations. 

Understanding the factors driving providers’ treatment decisions and/or payer coverage and HTA decisions allows for the development of strategies to address these issues, thereby removing hurdles to the patient access. Three specific areas of contemporary interest—agnostic therapy, cell and gene therapy, and RNA technologies—along with specific market access hurdles and the potential for the benefit of provider and/or payer insights are described below:

• Agnostic therapies: Tumor agnostic therapies can benefit rare subgroups of patients within traditionally recognized tumors. In these smaller populations, however, demonstrating value becomes more fragmented and stakeholder needs become more diverse. Importantly, provider and/or payer insights on these unique subpopulations, resulting in real-world evidence generation, can be used to help demonstrate meaningful value and supplement limited clinical trial evidence with these therapies allowing patients to gain timely market access. 
• Cell and gene therapy: While cell and gene therapies offer hope to patients suffering from rare, and/or serious diseases with a high unmet need, key market access issues with these therapies include those related to manufacturing, high cost, and potential long-term safety concerns. Pharmaceutical companies are working meticulously to fill the gaps, but manufacturing capacity often limits the number of patients who can be treated. Moreover, the high cost of these therapies is compounded by the fact that administration is concentrated over a short period of time, making it challenging for payers to absorb it. Finally, regulatory bodies and providers are looking to balance the benefits of early access to these innovative therapies with potential unknown long-term safety risks. There is a tremendous opportunity for real-world evidence generation to help answer these questions.
• RNA technologies: Successful market access to RNA technologies, specifically RNA interference drugs, relies on timely administration, accurate diagnosis of  rare diseases, patient education, and knowledge of clinical trials as often no standard of care exists, and commercial drug availability is evolving in the given therapeutic space. Proactive engagement of providers and payers to gain insights into disease burden can foster a stronger understanding of patient need and support evidence generation for possible value-based agreements. 

Appropriate selection of and timely access to all of these innovative therapies for cancer patients as well as patients with rare diseases in the clinic and hospital settings is critical for providers, while the high cost and budget impact of these therapies are a key focus area for payers. As such, it is important to understand the perspectives of both providers and payer decision makers on use and value of these therapies. Collection of oncology insights from both providers or payers in a virtual or live environment can aid manufacturers in preparing and overcoming the aforementioned oncology market access hurdles as emerging therapeutic approaches continue to enter into the market and positively impact the treatment landscape for patients with cancer.

The article should be referenced as follows: 

Hennenfent K, Shields K. Gaining real-world oncology insights from engagement of key opinion leaders through virtual and live solutions. HTA Quarterly. Fall 2021. https://www.xcenda.com/insights/htaq-fall-2021-real-world-oncology-insights

Sources:

• Couzin-Frankel J. Breakthrough of the year 2013. Cancer immunotherapy. Science. 2013;20;342(6165):1432-3. 
• Hackshaw MD, Holmes M, Lankford M, Thomas M, Ogbonnaya A, Eaddy M. Prescribing preferences in the first-line treatment for patients with metastatic renal cell carcinoma in the United States. Clin Genitourin Cancer. 2016;14(5):e479-e487.
• Hu B, Zhong L, Weng Y, et al. Therapeutic siRNA: state of the art. Sig Transduc Target Ther. 2020;5:101-126.
• Damase TR, Sukhovershin R, Boada C, Taraballi F, Pettigrew RI, Cooke JP. The limitless future of RNA therapeutics. Front Bioeng Biotechnol. 2021;9. doi: 10.3389/fbioe.2021.628137
• Tian Z, Liang G, Cui K, et al. Insight into the prospects for RNAi therapy of cancer. Front Pharmacol. 12:doi:10.3389.fphar.2021.644718
• Tsimberidou AM, Fountzilas E, Nikanjam M, Kurzrock R. Review of precision cancer medicine: evolution of the treatment paradigm. Cancer Treat Rev. 2020;86. doi:10.1016/j.ctrv.2020.102019
• Yang Y. Cancer immunotherapy: harnessing the immune system to battle cancer. J Clin Invest. 2015;125(9):3325-3337.
• Zhang Y, Zhang Z. The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications. Cell Mol Immunol. 2020;17:807-821.