Biomarker-Driven Care Is Racing Ahead of the Systems Built to Support It

Adjuvant CDK4/6 inhibitors are pushing breast cancer teams to build formal toxicity monitoring systems from scratch, fewer than two-thirds of high-risk patients with prostate cancer nationally are receiving guideline-recommended genomic testing, and multiple myeloma specialists are racing to move chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies out of academic medical centers and into the community—all while payers, tissue supply, and workforce capacity struggle to keep pace.

That was the through line across 4 panel discussions at an Institute for Value-Based Medicine^® event held by The American Journal of Managed Care^® in Pittsburgh, Pennsylvania, where clinicians from the University of Pittsburgh Medical Center (UPMC), Allegheny Health Network (AHN), the Veterans Affairs (VA) Pittsburgh Healthcare System, and West Virginia University (WVU) traded notes on breast, genitourinary (GU), hematologic, and lung malignancies.

Across all 4 sessions, a similar tension surfaced again and again: The science of precision oncology is advancing faster than the infrastructure, reimbursement pathways, and staffing needed to deliver it equitably. Circulating tumor DNA (ctDNA) testing captured that divide especially well, coming up in 3 of the 4 discussions. In breast cancer, it is used cautiously to guide de-escalation decisions; in GU cancers, it is being embraced more readily, both as a tiebreaker and alongside a newly FDA-approved adjuvant tool; and in lung cancer, one oncologist dismissed it as mostly unproven hype.

Breast Cancer: Adjuvant CDK4/6 Inhibitors Test the Limits of Monitoring Capacity

Moderator Adam Brufsky, MD, medical director of the Magee-Womens Cancer Program at UPMC, opened the evening by pressing panelists on how they manage patients now that CDK4/6 inhibitors—abemaciclib (Verzenio; Eli Lilly and Company) and ribociclib (Kisqali; Novartis), approved based on the monarchE (NCT03155997) and NATALEE (NCT03701334) trials, respectively^1-4—have moved into the adjuvant setting. Although abemaciclib is mostly reserved for a higher-risk population and ribociclib is used in a wider population of patients, Julia Foldi, MD, PhD, breast medical oncologist at UPMC Magee-Womens Hospital, said she can use these drugs interchangeably depending on which one a patient tolerates better.

The drugs available in the metastatic setting require more monitoring, which AHN handles with a dedicated team of nurses and pharmacists who conduct toxicity assessments and lab monitoring (much of it virtually) to keep patients out of the office, explained Danielle Roman, PharmD, BCOP, manager of oncology clinical pharmacy services at AHN. Shannon Puhalla, MD, assistant professor of medicine at the University of Pittsburgh School of Medicine and a medical oncologist and hematologist at UPMC Hillman Cancer Center (Hillman), takes a different approach.

“Sometimes you kind of feel that the only way to get things done is to schedule an office visit,” Puhalla said, adding that her practice schedules visits every 2 weeks for the first several months because toxicities are too easily missed otherwise. “I find that [for] those first 2 months, just scheduling office visits is the safest way to do it unless someone is super on top of things and trustworthy.”

The stakes are real: Foldi cited institutional data showing that approximately 40% of patients starting adjuvant abemaciclib discontinued treatment without ever undergoing a dose reduction first, which is evidence that toxicity is going unaddressed before patients simply quit. The panel also debated when ctDNA should influence treatment. Foldi said ctDNA status now outperforms pathologic complete response as a predictor of long-term outcomes in triple-negative disease, although the group agreed the data are not yet mature enough to use ctDNA results to withhold CDK4/6 inhibitors or capecitabine outside of select cases.

Looking ahead, the panelists flagged oral selective estrogen receptor degraders (SERDs) and antibody-drug conjugate (ADC) sequencing as the next flash points, with Roman warning that oral SERDs moving into earlier lines will “present some unique challenges with cost of care.”

Testing Gaps Persist in GU Oncology as Targeted Therapy Reshapes Practice

Moderator Shifeng Mao, MD, of AHN, guided a discussion on how biomarker testing has transformed prostate and bladder cancer care while exposing stark access gaps. Prostate-specific membrane antigen (PSMA) PET imaging has changed staging decisions so significantly that it’s a burden on the system, said Quoc-Dien Trinh, MD, chair of the Department of Urology at the University of Pittsburgh School of Medicine and chair of urology at UPMC.

“We’re ordering so many PSMA PET [that] we’re taxing the system.… [The radiologists] just can’t keep up, and we’re having a lot of access issues,” Trinh said, noting that scans are now catching occult metastatic disease in patients who previously would have gone straight to surgery.

Leonard Appleman, MD, PhD, associate professor of medicine and director of the genitourinary cancer disease section at the University of Pittsburgh, said germline testing can take approximately 3 months to process, a bottleneck Trinh linked to a broader access problem as testing volume has expanded from a handful of patients to hundreds.

Nationally, Mao noted, only approximately 50% to 60% of patients with high-risk prostate cancer receive recommended next-generation sequencing,^5,6 a gap Bana Antonios, MD, of AHN (now with Loyola Medicine), attributed partly to fragmented ordering practices and inconsistent panel interpretation across practices that don’t specialize in GU cancers. Reflex testing built into pathology workflows and electronic health record order sets, as Trinh described from his prior institution, was cited as one fix.

The panelists also raised the financial side of testing. Despite assurances from testing companies that patients will not be billed, Mao said patients still occasionally show up with bills for several thousand dollars. In bladder cancer, Antonios pointed to HER2 immunohistochemistry and FGFR3 alterations as increasingly actionable targets, borrowing ADCs such as trastuzumab deruxtecan (Enhertu; AstraZeneca) from breast cancer, and commented that ctDNA-guided approaches created a lot of conversation at the 2026 American Society of Clinical Oncology Annual Meeting. Appleman is using ctDNA as a tiebreaker in the advanced setting if risks and benefits of a treatment decision are closely balanced.

“I think everybody will be excited about more ctDNA‑guided approaches—mostly in the early stages—to guide our therapies,” Antonios said. “Are we getting closer to potentially sparing people cystectomies? I don’t know how soon that will be, but that’s the hope.”

CAR T and Bispecifics Push Into the Community for Multiple Myeloma

With 2 CAR T-cell therapies and 4 bispecific antibodies now approved in multiple myeloma, clinicians must weigh patient characteristics to choose between the 2 modalities. Konstantinos Sdrimas, MD, associate professor in the Department of Medical Oncology at WVU, said he prioritizes CAR T-cell therapy, when possible, given its higher complete response rates, particularly with ciltacabtagene autoleucel. However, Salman Fazal, MD, hematology lead at UPMC Hillman Cancer Center, said real-world logistics, such as rapidly progressing disease, transportation barriers, or caregiver limitations in older patients, often push care toward bispecifics instead.

“If a patient is progressing rather quickly…it’s easy to start the patients on bispecifics quickly, and that always plays [a role] in terms of decision‑making,” Fazal said.

Outpatient administration is becoming standard for bispecifics, with Sdrimas describing a model in which patients complete step-up dosing near WVU while staying in nearby housing and walking to the infusion center daily. Fazal said his program has successfully treated select patients on an outpatient basis using prophylactic tocilizumab, although he cautioned that a single severe toxicity event “could really jeopardize the outpatient administration” of the whole program.

Cyrus Khan, MD, staff physician in hematology/oncology at Hillman, recently moved from a center that takes referrals in Pittsburgh to a position further out in the community, and he sees a difference.

“Honestly, patients just don’t want to travel, come to Pittsburgh, get admitted to the hospital,” he said. “One of the more important things to do is to push it to the community setting so the patients can get benefit from it. Otherwise, they won’t come for bispecifics. They won’t come for CAR T, either.”

The panelists reported few payer roadblocks on drug approvals themselves, but Fazal and Jeff Goff, RPh, MS, senior director of pharmacy and global oncology services at Hillman, both said prior authorization is still routinely required for hospital admission or tocilizumab use to manage cytokine release syndrome. Goff added that CAR T-cell costs could fall substantially if US hospitals adopt the point-of-care manufacturing model already used in parts of Europe. “It’s a third” of the cost, he said.

Asked what they’re most looking forward to, the panelists pointed to minimal residual disease–guided, time-limited therapy and CAR T-cell therapy moving into first-line treatment.

“I remember sitting in the room when I learned about CAR T for the first time, and I turned to the person next to me and said, ‘Remember where you were when you heard this,’” Goff said.

Testing Infrastructure for Lung Cancer Varies Widely, and Financial Toxicity Looms Large

The final panel, moderated by Jeremy Pappacena, PharmD, BCOP, clinical pharmacy specialist at AHN, examined why comprehensive genomic profiling—now standard of care for nonsquamous non–small cell lung cancer (NSCLC)—still isn’t reaching every eligible patient. James Herman, MD, associate director of the Hematology/Oncology Fellowship Program at the University of Pittsburgh and oncologist in the Division of Hematology and Oncology at the VA Pittsburgh Healthcare System, said the VA’s decision 5 years ago to centrally fund testing for every indicated patient has produced what he estimated is 100% testing adherence, compared with UPMC’s reflex, pathology-driven model, which he said is also an effective method if it is done properly.

The in-house 500-plus gene panel at Hillman typically returns results within 10 to 14 days, fast enough to have answers ready before a patient’s first treatment-planning visit, said Laura Stabile, PhD, associate professor of pharmacology and chemical biology at the University of Pittsburgh. Jennifer Niccolai, PharmD, BCOP, a clinical pharmacy specialist at AHN, said ordering there still depends heavily on individual physicians entering staging information correctly to trigger the right test, which can “also impact the turnaround time of that [test result] significantly.”

Testing strategy also shifts depending on where a patient is in treatment, the panelists said. In the neoadjuvant setting, Herman said his team specifically wants to rule out EGFR and ALK alterations before starting patients on immunotherapy, as those patients tend to do worse on checkpoint inhibitors and can have unexpected toxicity if they later switch to a targeted therapy. Stabile added that limited specimen size from lung biopsies is the other reason comprehensive panels make more sense than single-gene tests in most cases. When comprehensive testing fails because there isn’t enough tissue, Herman said he’ll ask the pathologist to prioritize the 2 or 3 genes he thinks are most likely to be relevant rather than lose the sample entirely.

“It’s a guess, but you’re trying to get something rather than getting a failed [test],” he said.

For patients who need a second liquid biopsy because the first tissue sample was insufficient, Herman said the decision to pursue it is individualized based on age, smoking history, and the likelihood of finding an actionable mutation.

“[If the patient is a] heavy smoker, I mostly want to know about KRAS right now,” he said, noting that a full panel isn’t worth the delay for every patient. “It’s balancing the benefit of another biopsy vs the risk of another biopsy, the inconvenience, and the delay in getting things going.”

The panel spent significant time on affordability. With some targeted therapies now extending into the adjuvant setting for early-stage, fully resected disease, Herman said patients face 2 to 3 years of treatment with no evidence of remaining cancer—and co-pays that can reach 20% of a $15,000 monthly drug cost.

“It’s a huge issue,” he said. He added that this is even a challenge in the metastatic setting, where drugs are now keeping patients alive 2 to 5 years down the road. “They’re great drugs, but there’s just a cost.”

Niccolai said insurance instability compounds the problem because patients can lose coverage for medications keeping them alive after a job or policy change. Stabile also described cases in which insurers cover only 1 of several FDA-approved options for ALK-positive NSCLC despite newer trial data. Pappacena recalled a patient whose insurer preferred alectinib (Alecensa; Genentech) over lorlatinib (Lorbrena; Pfizer), the drug his team wanted to start based on the phase 3 CROWN trial (NCT03052608).^7,8

On ctDNA, Herman was more skeptical than his GU and breast oncology colleagues earlier in the evening, saying the technology has proven itself mainly in colorectal cancer and hasn’t yet been shown to change outcomes in lung cancer, even though he sees promise in using it to guide the duration of maintenance immunotherapy after chemoradiation and to monitor patients through neoadjuvant chemoimmunotherapy and surgery.

“I think there’s a lot of talk and there’s a lot of smoke, but there’s not a lot of fire underneath it, for sure,” he said of ctDNA’s current role in lung cancer.

References

1. FDA approves Verzenio (abemaciclib) as the first and only CDK4/6 inhibitor for certain people with HR+ HER2- high risk early breast cancer. News release. Eli Lilly & Company. October 13, 2021. Accessed September 9, 2026. https://investor.lilly.com/news-releases/news-release-details/fda-approves-verzenior-abemaciclib-first-and-only-cdk46

2. Johnston SRD, Toi M, O’Shaughnessy J, et al; monarchE Committee Members. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. 2023;24(1):77-90. doi:10.1016/S1470-2045(22)00694-5

3. Santoro C. FDA approves ribociclib for early breast cancer treatment with high recurrence rate. AJMC. September 17, 2024. Accessed September 10, 2026. https://www.ajmc.com/view/fda-approves-ribociclib-for-early-breast-cancer-treatment-with-high-recurrence-rate

4. Slamon D, Lipatov O, Nowecki Z, et al. Ribociclib plus endocrine therapy in early breast cancer. N Engl J Med. 2024;390(12):1080-1091. doi:10.1056/NEJMoa2305488

5. Klugman MF, Tsai HL, Iranmanesh Y, et al. A comparison of characteristics and outcomes of metastatic prostate cancer patients with and without next-generation sequencing testing. JCO Oncol Pract. Published online February 19, 2026. doi:10.1200/OP-25-00688

6. Hage Chehade C, Jo Y, Gebrael G, et al. Trends and disparities in next-generation sequencing in metastatic prostate and urothelial cancers. JAMA Netw Open. 2024;7(7):e2423186. doi:10.1001/jamanetworkopen.2024.23186

7. Shaw AT, Solomon BJ, Felip E, et al. Lorlatinib versus crizotinib as first-line treatment for advanced ALK-positive non-small-cell lung cancer: 7-year update from the phase III CROWN study. Ann Oncol. 2026;37(9):1242-1252. doi:10.1016/j.annonc.2026.05.692

8. Garcia C, Abrahami D, Polli A, et al. Comparative efficacy and safety of lorlatinib versus alectinib and lorlatinib versus brigatinib for ALK-positive advanced/metastatic NSCLC: matching-adjusted indirect comparisons. Clin Lung Cancer. 2024;25(7):634-642. doi:10.1016/j.cllc.2024.08.003