Cancer Care in Transition: Navigating Breakthrough Therapies Amid Economic Strain

Cancer care is entering an era characterized by extraordinary scientific innovation alongside significant financial challenges. During a recent Institute for Value-Based Medicine (IVBM) event in Orange County, California, panelists explored how advances in multiple myeloma, breast cancer, non–small cell lung cancer (NSCLC), and health equity are reshaping clinical decision-making and the economics of cancer care. Across discussions of smoldering myeloma, circulating tumor DNA (ctDNA), antibody-drug conjugates (ADCs), and immunotherapy, the panelists explored how innovation in cancer care is moving faster than the systems designed to deliver and pay for it.

During the 4 discussions, panelists highlighted the growing need to balance cutting-edge therapies with sustainable models of access while addressing disparities that leave some patients behind. From the evolving role of chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies to the challenges of biomarker testing and the impact of social determinants of health (SDOH), the panelists underscored that the promise of precision medicine will only be realized if affordability, infrastructure, and equity remain at the forefront of cancer care.

The Evolving Cost of Multiple Myeloma Care

The opening panel examined the tension between the expanding landscape of therapies in multiple myeloma and the financial realities of managing a disease where therapy often continues indefinitely. Panelists included Amrita Krishnan, MD, director of the Judy and Bernard Briskin Multiple Myeloma Center and professor of hematology/hematopoietic cell transplantation at City of Hope in Duarte, California; Ann Mohrbacher, MD, medical director of autologous bone marrow transplant, associate professor of clinical medicine and chair of the Biomedical Institutional Review Board 2 at the Keck School of Medicine of the University of Southern California (USC) in Los Angeles; Amitabha Mazumder, MD, a medical oncologist at The Oncology Institute of Hope & Innovation in Glendale, California; and Tiffany Phung, PharmD, director of specialty pharmacy, value, trade relations, and market access at UC Davis Health in California. The panelists also explored current controversies in smoldering myeloma management, the expanding role of CAR T-cell therapy, and the promise of bispecific antibodies.

Smoldering myeloma. Smoldering myeloma has become one of the most debated areas in practice, particularly since the release of results from the phase 3 AQUILA trial (NCT03301220),¹ according to Krishnan. “Smoldering myeloma is generally at least a 1-hour consult, and it has become even more complicated with the data many of you are familiar with from the AQUILA study, which showed a benefit of CD38-targeted therapy for [patients with] high-risk smoldering myeloma,” Krishnan said.

Mohrbacher added that she generally favors observation but acknowledged that immunotherapy offers a more rational approach than using older agents. Phung noted that daratumumab (Darzalex; Janssen) and lenalidomide (Revlimid; Bristol Myers Squibb) are options, although insurers are often reluctant to cover them outside of clinical trials.

“Basically, at this point, I think there are 2 approaches,” Phung said. “One is whether to use daratumumab or lenalidomide as treatment for smoldering disease, or whether to use a combination. At this point, there are no data for that. I think I’d have a tough time convincing insurance companies to approve daratumumab—certainly not daratumumab and [subcutaneous daratumumab]. We’re still trying to see whether we can join clinical trials.”

Mohrbacher also raised concerns about lead-time bias and emphasized the need for genomic risk stratification. “If we’re talking about economic considerations, has it been easier to get lenalidomide approved? I don’t know what your experience has been,” she said. “It’s also very expensive to use prophylactically, and you don’t know whether you’re just creating lead-time bias—just deferring disease a little and not necessarily changing what [the patient’s] 10-year outlook is. I look to the Europeans for that, because they keep track of patients over their entire lifetime.”

However, Krishnan pointed out that preventing active myeloma could reduce the higher costs associated with advanced disease, although not all high-risk patients progress. “The clinical data do seem to be pretty strong from the AQUILA study,” Krishnan said. “From an economic standpoint, obviously, these are expensive agents. If you look at it, not every high-risk patient is going to progress. That’s one challenge. On the other hand, you could argue you are preventing active myeloma, which has a much higher burden of care and cost.”

CAR T-cell therapy vs transplant. CAR T-cell therapy has become increasingly viable in earlier lines of treatment. Krishnan said City of Hope offers it as early as the second line for high-risk or CD38-refractory patients. Mohrbacher noted that some older patients unfit for autologous transplant may still be candidates for CAR T, which can deliver durable remissions through a one-time intervention. She added that although stem cell transplant is relatively inexpensive compared with ongoing quadruplet therapy, CAR T’s potential to eliminate years of costly maintenance makes it a strong option.

Phung explained that prior response often guides selection: Patients who respond poorly to frontline therapy may move to CAR T earlier. However, the panel acknowledged the enormous upfront cost of CAR T, noting that lenalidomide maintenance alone can exceed $100,000 per year, underscoring the need to consider lifetime cost.

Bispecific antibodies and access. As a class, bispecific antibodies were described as promising. But getting access can be limited by acquisition cost and intensive monitoring requirements. Mazumder emphasized the need for infrastructure to manage cytokine release syndrome, infection risk, and hypogammaglobulinemia. Mohrbacher added that referring physicians are often hesitant to transition patients back to community care after they start these therapies. “Bispecifics are coming fast,” Mohrbacher said. “Referring doctors are still hesitant to take patients back into the community after bispecifics—that’s been a barrier.”

Phung said her health system is building capacity to expand access, including partnerships that allow patients to continue therapy in community settings once they are stable. “We’re actually working with centers to bring patients back into the community right after initiation,” she said.

This discussion framed the core tension in myeloma care: Innovation continues to accelerate, but affordability and delivery models have not caught up.

Advancing Access to Personalized Breast Cancer Care
The second panel brought together Joanne Mortimer, MD, FACP, FASCO, director of Women’s Cancers Program, vice chair and professor in the Department of Medical Oncology and Therapeutics Research, and Baum Family Professor in Women’s Cancers at City of Hope; Oranus Mohammadi, MD, a medical oncologist at The Oncology Institute of Hope & Innovation; and Irene Kang, MD, a medical oncologist, assistant professor, and director of Women’s Health Medical Oncology at City of Hope, to discuss how innovations such as ctDNA testing, ADCs, and CDK4/6 inhibitors are reshaping the treatment of breast cancer. Their discussion highlighted not only the clinical impact of these tools but also the logistical and financial hurdles that continue to limit access for many patients.

Promise and limits of ctDNA. Mohammadi described routine ctDNA testing at metastatic diagnosis, particularly in hormone receptor–positive (HR+), HER2-negative (HER–) patients whose ESR1 and PIK3CA mutations influence therapy. He acknowledged, however, that serial testing every 8 to 12 weeks, as performed in trials, is impractical for most community practices.

Kang brought up results from the phase 3 SERENA-6 trial (NCT04964934), in which patients on aromatase inhibitors and CDK4/6 inhibitors underwent serial ctDNA testing.² When ESR1 mutations were detected, patients were switched to camizestrant (AstraZeneca) even without radiographic progression. Although the trial results showed progression-free survival (PFS) benefit, Kang noted logistical burdens and uncertain overall survival impact.

Mortimer added that ctDNA is most useful in cases where radiographic monitoring is difficult, such as lobular breast cancer or bone-only disease. Yet despite advances, the panel agreed that imaging remains the standard trigger for treatment change.

ADCs: Redefining treatment pathways. ADCs dominated the discussion, with panelists describing transformative outcomes across multiple subtypes. Kang called trastuzumab deruxtecan (Enhertu; AstraZeneca/Daiichi Sankyo) her first choice for HER2-low patients.

“With trastuzumab deruxtecan in HER2-positive metastatic disease, it’s sort of no question—there’s no other available agent that compares, and it’s incredibly active,” Kang said.

“But for HR+, HER2– but HER2-low disease, the DESTINY-Breast studies demonstrated really impressive PFS benefit and improvements over standard chemotherapy for patients whose tumors had developed resistance to endocrine therapy. Your first-line chemotherapy question—should it be trastuzumab deruxtecan [or] other available chemotherapy agents? Including subgroup analyses, patients with bone-only disease—patients you might expect to do fine on less-intensive therapy—still benefited from trastuzumab deruxtecan. So that’s my go-to in the HR+, HER2-low population.”

Mohammadi said sacituzumab govitecan (Trodelvy; Gilead Sciences) remains his go-to in triple-negative breast cancer, supported by results from the phase 3 ASCENT trial (NCT02574455).3 Both Mohammadi and Kang also mentioned datopotamab deruxtecan (Datroway; AstraZeneca/Daiichi Sankyo), which was approved by the FDA after demonstrating efficacy in HR+, HER2– patients, although it is associated with toxicities such as stomatitis and mucositis.
Mortimer reflected on the dramatic response rates seen with trastuzumab deruxtecan, noting that the drug has reshaped expectations in metastatic disease, where survival advantages are rare. The panel also raised challenges in HER2 testing, as older pathology reports often lack granularity, requiring retesting to determine ultralow HER2 status. Kang urged laboratories to update workflows to ensure timely access to ADCs.

Advancing Equitable Access to NSCLC Therapies

Moderated by Joseph Alvarnas, MD, professor of hematology and vice president of government affairs at City of Hope, the NSCLC panel featured Jorge Nieva, MD, associate professor of clinical medicine at Keck School of Medicine of USC; Aaron Lisberg, MD, assistant professor of clinical medicine at UCLA; and Lauren Antrim, MD, assistant clinical professor in the Department of Medical Oncology and Therapeutics Research at City of Hope, who examined the complexities of biomarker testing, payer-driven inequities, and the expanding role of immunotherapy in NSCLC. Their discussion underscored how rapid scientific progress is colliding with systemic barriers, raising questions about equity, infrastructure, and the role of artificial intelligence (AI) in guiding treatment decisions.

Biomarker testing and systemic barriers. Nieva stressed that reliance on small-gauge CT-guided biopsies often results in insufficient samples, producing false negatives for actionable mutations. He advocated for bronchoscopic biopsies, which provide higher yields for next-generation sequencing.

“We have inadequate tissue, in large part because we still have a culture where the CT-guided lung biopsy is the easiest test to order,” Nieva said. “We need to develop a culture where we know what disease the patient has, and we use techniques that actually have good yield for biomarker testing. There are not that many interventional pulmonologists across the country, so we need to be able to do biopsies bronchoscopically, which is where the highest yield is. That would be my pitch to solve this problem, which I think is largely cultural.”

Lisberg pointed out that new approvals—such as MET inhibitors via immunohistochemistry (IHC) and HER2-targeted therapies—require more robust testing. “In the NSCLC space, with recent approvals that require even more testing, we have MET approval based on IHC, as well as the pan-tumor HER2 overexpression approval. There are iterative questions [relating to barriers to adequate biomarker testing] that we continue to ask, especially in the context of PD-L1, which we certainly need to guide our immunotherapy decisions,” Lisberg said.

Yet systemic inequities persist. Nieva described the disparity between USC’s private system, where simultaneous tissue and blood testing is routine, and the county hospital system, where sequential testing and payer restrictions delay care. Lisberg added that such inequities are unacceptable, especially
within the same city.

Interpretation and the role of AI. Antrim praised the National Comprehensive Cancer Network (NCCN) guidelines and new AI tools such as OpenEvidence, which assist in mutation interpretation. “The NCCN guidelines are phenomenal, and very helpful. They can tell you [in the] first line, potentially start with these drugs vs second-line [therapies]. For example, HER2-mutated disease is usually treated in the second line. That’s very helpful,” Antrim said. “There are also really good AI tools now, such as OpenEvidence and others, that you can probe to try to identify what mutations are potentially targetable vs something like TP53, where it’s really a clinical trial situation.”

Lisberg noted that vendor reports are increasingly helpful in matching patients to trials. Still, Nieva warned that community oncologists cannot master the nuance of every tumor type, making subspecialization within practices essential.

Immunotherapy in early and advanced disease. Immunotherapy uptake has risen sharply, with survival gains of more than 50% in stage IV disease between 2010 and 2020. Antrim cited International Association for the Study of Lung Cancer consensus statements supporting neoadjuvant chemo-immunotherapy for patients with stage II or IIIA disease without EGFR or ALK alterations. Nieva argued that, biologically, neoadjuvant therapy has advantages, but practical barriers often push patients and surgeons toward immediate surgery.

The panelists also addressed discontinuation of immunotherapy after prolonged benefit. Nieva said he revisits the option at each visit, eventually persuading patients to stop. Lisberg emphasized that patient autonomy is central, noting many patients refuse to discontinue effective therapy.

Rewriting the Rules of Equity in Cancer Care
The final panel, featuring Yale Podnos, MD, MPH, FACS, chief medical officer at The Oncology Institute of Hope & Innovation; Daniel Virnich, MD, MBA, FACHE, CEO of The Oncology Institute of Hope & Innovation; Idoroenyi Amanam, MD, assistant professor of the Department of Hematology and Hematopoietic Cell Transplantation at City of Hope; and Alvarnas, tied together the themes of innovation and cost with a focus on equity. Their conversation emphasized
the critical role of SDOH, the need for inclusive genomic and clinical trial strategies, and the importance of training future clinicians to
deliver patient-centered care in diverse communities.

SDOH and outcomes. Amanam explained that transportation, housing, and language barriers directly affect patients’ transplant success. His team addresses these barriers through partnerships and multilingual staffing, enabling outcomes for disadvantaged patients comparable to national averages.

“From a transplant perspective, SDOH are definitely not an abstract issue. They actually determine which patients go to transplant and whether transplant is successful. You think about transportation, lodging, housing, language—living in Southern California, we have a very diverse population. These factors play a big role in determining how patients will do,” Amanam said. “On a national level, the data are mixed. Some show that social determinants are an independent predictor for poor transplant outcomes; others show no difference. We’ve been collecting a lot of data, but we haven’t
been taking action to use it to improve outcomes.”

Virnich stressed that financial strain delays treatment for most patients, often due to ancillary costs such as transportation. “Most people aren’t familiar with the national data on how much SDOH impact cancer care, quality, and access. Three-quarters of patients treated for cancer actually delay the start of therapy because they don’t have the money to meet their out-of-pocket spend, and oftentimes it’s not just the $2000 co-pay for chemotherapy—it’s that they can’t afford the bus or the ride to the clinic. It’s wide-ranging, and we see it every day. There are solutions, but it’s definitely a widespread problem across the industry,” Virnich said.

Alvarnas cited American Association for Cancer Research data showing that eliminating adverse SDOH could improve survival by 30%, but he argued that federal programs such as Medicaid often obstruct support by classifying transportation subsidies as inducements.

“I spend my life dealing with Medicare and Medicaid policies, and here’s an example: If a Medicaid patient can’t get to the clinic, we could theoretically provide gas money. But it’s illegal. It’s considered an inducement. Many logistical rules meant to prevent fraud actually make these programs inhospitable for the most vulnerable patients,” Alvarnas said. “If you were designing the system, you wouldn’t start by reverse-engineering dollars to make it fraud-proof. You’d start with the patient and family, building trust, ease, compassion, and convenience into the system. Medicare and Medicaid both need a profound reset to better reflect the needs of patients and families.”

Race, ancestry, and genomics. The panel distinguished between race as a social determinant and ancestry as a biological factor. Amanam called for predictive models integrating genomic, social, and clinical data to better identify high-risk populations. Alvarnas pointed to genomic sequencing initiatives at the Translational Genomics Research Institute (TGen) in Phoenix, Arizona, which capture biodiversity to guide drug metabolism, toxicity, and efficacy predictions.

“TGen, which is part of the City of Hope family, does genomic sequencing across a broad array of patients to capture adequate biodiversity,” Alvarnas said. “Just because someone looks a certain way or is labeled a certain way doesn’t determine the genomics that influence drug metabolism, germline mutations affecting toxicity, or likelihood of benefit. The same is true for somatic mutations. The only way to approach this is systematically.”

Clinical trials and trust. Virnich described placing trials in community settings with culturally tailored communication to improve enrollment among underserved groups. Amanam added that barriers also exist relating to strict eligibility criteria, transportation, and mistrust of physicians.

“For some trials, eligibility criteria are very strict, and that’s a problem for many patients,” Amanam said. “Distance is another. Take Los Angeles, for example: City of Hope is a multicenter institution, but most trials are run on the main campus. If you live in South [Los Angeles] and have an 11 am appointment, it might take you 2 hours to get there. If you don’t have a vehicle, how do you get transportation?”

Alvarnas emphasized the need to restructure clinical trial systems to meet patients where they are, rather than expecting them to navigate opaque systems. “The way the system largely works now, patients are expected to jump into our universe and surrender themselves to a highly complex system. But the right paradigm is that we meet patients within their own journey,” Alvarnas said. “That requires resetting our systems to be much more patient-focused, not system-focused.”

Training the next generation. The panelists concluded by reflecting on physician training. Virnich called for greater exposure to underserved settings during residency and fellowship. Alvarnas recalled mentors who modeled patient-centered leadership, contrasting those with research-focused institutions where clinical care was undervalued. Changing reward systems, he argued, is essential to making equity a priority.

Conclusion
The discussions at the Orange County IVBM event underscored that the next decade of cancer care will be defined as much by how systems adapt as by how science advances. Breakthroughs in multiple myeloma, breast cancer, and NSCLC are offering unprecedented opportunities to extend and improve lives, yet their promise can only be realized if access, affordability, and infrastructure evolve in step with innovation. Panelists emphasized that equity must remain a central priority, from addressing SDOH to ensuring inclusive clinical trials and sustainable financing models. As precision medicine accelerates, the challenge for clinicians, health systems, policy makers, and payers will be to build a framework where cutting-edge therapies are not only scientifically possible but also practically and fairly available to every patient who needs them.

References
1. A study of subcutaneous daratumumab versus active monitoring in participants with high-risk smoldering multiple myeloma. ClinicalTrials.gov. Updated August 17, 2025. Accessed September 3, 2025. https://clinicaltrials.gov/study/NCT03301220
2. Phase III study to assess AZD9833+ CDK4/​6 inhibitor in HR+/​HER2-MBC with detectable ESR1m before progression (SERENA-6) (SERENA-6). ClinicalTrials.gov. Updated July 16, 2025. Accessed September 3, 2025. https://clinicaltrials.gov/study/NCT04964934
3. Trial of sacituzumab govitecan in participants with refractory/​relapsed metastatic triple-negative breast cancer (TNBC) (ASCENT). ClinicalTrials.gov. Updated June 15, 2022. Accessed September 3, 2025. https://clinicaltrials.gov/study/NCT02574455