Oncologists Grapple With Sequencing, Access as Treatments Multiply

Matching an expanding menu of targeted drugs, antibody-drug conjugates (ADCs), and biomarker tests to the right patient, while also keeping insurers, caregivers, and social barriers from getting in the way, is increasingly challenging, experts explained during 4 panels at an Institute for Value-Based Medicine^® event held in the Detroit, Michigan, area and hosted by The American Journal of Managed Care^®.

Physicians and pharmacists from Henry Ford Cancer (Henry Ford), Karmanos Cancer Institute (Karmanos), Corewell Health, Trinity Health Oakland/IHA, the VA Detroit Healthcare System, and the University of Michigan/Ann Arbor VA walked through how they are sequencing new therapies in chronic lymphocytic leukemia (CLL), breast cancer, and lung cancer, plus how social determinants of health can derail even the best-laid treatment plan.

An “Embarrassment of Riches” in CLL

With a growing list of Bruton tyrosine kinase (BTK) inhibitors and fixed-duration, venetoclax-based regimens for patients with CLL, clinicians have more choices when selecting treatment, said experts in the opening panel, moderated by Ahmad Mattour, MD, a hematologist-oncologist at Henry Ford. Mohammad M. Chisti, MD, a hematologist-oncologist at Corewell Health William Beaumont University Hospital, said cardiovascular risk is usually the first filter he applies, followed by tolerability, disease biology, and drug-drug interactions, before he factors in patient preference.

“When you give options, it’s like a menu card in a restaurant. And when they look at it, what’s the [easiest] one?” Chisti said.

High-risk features such as TP53 mutations or 17p deletion tend to push Chisti toward continuous BTK inhibitor therapy rather than a fixed-duration course, he said, whereas patients with cardiovascular disease, renal impairment, or frailty may be better served by a shorter, time-limited regimen. Mattour noted that emerging tools such as minimal residual disease testing are helping clinicians gauge depth of response, though he questioned whether continuous treatment is “comforting to the patient or comforting to ourselves as the treating physicians.”

Qianyao Qiu, PharmD, BCOP, an oncology clinical pharmacy specialist at Karmanos, said her team leans heavily on a 4-part workup for patients starting oral oncolytics: medication access, education, drug interaction evaluation, and toxicity management. Because BTK inhibitors carry antiplatelet effects, she said pharmacists pay particular attention to older patients already on anticoagulation for atrial fibrillation.

Her specialty pharmacy handles prior authorizations directly and can usually get a new prescription filled within days, she said, although insurer-mandated step therapy—including cases in which plans push ibrutinib ahead of newer, better-tolerated options—remains a recurring holdup, sometimes requiring a peer-to-peer call and supporting literature before approval comes through.

Chisti added that a dedicated specialty pharmacy navigator, paired with shared decision-making about a patient’s tolerance for chronic therapy, has made a meaningful difference in matching “the right drug for the right patient.” Distance from the infusion center also factors into the choice between oral and intravenous options.

“Oral is exciting, like zanubrutinib [Brukinsa; BeOne Medicines],” Chisti said. “I have patients [who] live 3 [or] 4 hours away, and they will just do video visits and send the labs by fax or do the local labs, so it works well.”

Sequencing a Crowded Field of ADCs in Breast Cancer

With trastuzumab deruxtecan (T-DXd; Enhertu; Daiichi Sankyo) now paired with pertuzumab (Perjeta; Genentech) as a first-line option in HER2-positive metastatic breast cancer¹—joining sacituzumab govitecan (Trodelvy; Gilead Sciences) and datopotamab deruxtecan (Datroway; Daiichi Sankyo) across HER2-low and triple-negative disease^2,3—oncologists at Henry Ford are increasingly confronting how to sequence multiple ADCs in the same patient. Moderator Rebecca Chacko, MD, said many of the panel’s questions come directly from the group’s weekly breast cancer meetings.

Vrushali Dabak, MD, said a retrospective review of her institution’s own data found that using ADC after ADC tends to produce a weaker response from the second agent, prompting her to consider what can be used instead. Haythem Ali, MD, said schedule and adverse event profile should drive the choice among agents once resistance patterns are considered.

“The imagination stops with the payload,” Ali said, noting that most of an ADC’s activity and its toxicity comes from the drug attached to the antibody rather than the antibody itself. “When you sequence, you have to move away from the mechanism of action that you just used,” he added.

Monitoring for those toxicities is intensive. For patients receiving T-DXd, Hiba Jabbour-Aida, MD, said she orders high-resolution chest CT scans every 6 to 8 weeks to catch interstitial lung disease, as well as echocardiograms every 3 months. She also monitors closely for neutropenia with sacituzumab govitecan and manages persistent, delayed nausea, which can require adjusting premedication regimens.

Insurance remains a persistent obstacle, the panelists agreed, although less so for the ADCs themselves than for companion targeted agents. Medicaid spend-down requirements pose another hurdle: Chacko said they can force patients to come up with several thousand dollars before coverage kicks in, regardless of which treatment they receive.

Jabbour-Aida said she has run into more resistance getting targeted agents such as capivasertib (Truqap; AstraZeneca) approved than ADCs, as some payers require patients to first fail an older drug like alpelisib (Piqray; Novartis). “Even when you try to appeal, sometimes you cannot get them to approve the drug that you want,” she said.

With constant therapy updates happening in the space, patients are educating themselves and asking about new regimens, Chacko said. “We’re in a space where patients are almost getting real-time updates in the same time that we are, and we do have to be finding ways to be prepared to get that authorization without delaying the patient’s care,” she said.

However, clinicians also have to manage patient expectations. There are a lot of new regimens, but protocols need to be in place to ensure adherence and toxicity management, Chacko added. Henry Ford has a nurse program with pharmacists specializing in oral chemotherapy to check the drug interactions after they are prescribed and then check with insurance to get the drug authorized, Jabbour-Aida explained.

Closing Community-Academic Gaps in Lung Cancer Biomarker Testing

In lung cancer, comprehensive genomic testing is now essential before starting treatment, said Nithya Ramnath, MD, a professor at the University of Michigan and section chief of oncology at the Ann Arbor VA, during the third panel, moderated by Ammar Sukari, MD, chief of the Division of Medical Oncology at Karmanos. Ramnath pointed to the VA’s own experience: A dedicated precision oncology program increased testing rates for veterans with lung cancer over 5 years through reflex testing pathways.⁴

Bindu Potugari, MD, a thoracic oncologist at Henry Ford, said she now orders next-generation sequencing for essentially all patients regardless of histology, having caught targetable alterations, including EGFR and MET exon 14 skipping mutations, even in squamous and small cell histologies where such findings are rare. Turnaround time and insurance denials remain her biggest obstacles, she said, along with getting newly approved drugs into patients’ hands once a mutation is identified; she described trying twice, unsuccessfully, to obtain sunvozertinib (Zegfrovy; Dizal Pharma) for a patient with an EGFR exon 20 insertion.

“They are approving the drugs, but we have to think about [whether] we have access to the drug,” Potugari said.

Community practices without a dedicated thoracic pathologist or interventional pulmonologist can still close the testing gap by pushing biopsy teams to collect more tissue up front and by leaning on liquid biopsy platforms when repeat sampling isn’t feasible, said Potugari and Ali, who stayed on from the previous breast cancer panel. Ali added that financial barriers are more pronounced with in-house testing panels, which tend to have less patient assistance support than external platforms such as Tempus or Foundation Medicine.

“It’s really hard for me to just keep dumping patients [who] have financial issues on the outside companies, but you do what you have to do,” Ali said.

The panelists broadly agreed that toxicity management has grown more complex alongside the expanding drug list. Ramnath said 2 patients receiving immunotherapy in their clinics have died, underscoring why she uses a stricter biomarker cutoff than current labeling requires before starting adjuvant immunotherapy. Ali said building prophylactic medications directly into chemotherapy order sets, rather than relying on memory, has cut down on avoidable complications, and Potugari credited a clinical pharmacist who calls patients weekly to see how they’re doing and making sure they are adhering to their regimen.

Confronting Social Barriers That Undercut Clinical Progress

The final panel turned from what happens inside the exam room to what happens outside it. Social needs such as transportation, housing, and food insecurity “can derail the best laid plans,” said moderator Garth Strohbehn, MD, MPhil, an assistant professor at the University of Michigan and staff oncologist at the Ann Arbor VA. Isabela Mazur, PharmD, a clinical pharmacy practitioner at the Detroit VA and Henry Ford Health, said universal screening at treatment initiation, followed by direct connection to social work resources, has proven essential for a veteran population that often lives alone with limited family support.

Ibrahim Azar, MD, a medical oncologist with Trinity Health Oakland/IHA, said community oncology carries its own advantages despite fewer formal resources than academic centers, including smaller staffs and closer relationships with patients that can surface unspoken barriers to care. Phoebe Tsao, MD, a physician at the University of Michigan and Ann Arbor VA, pointed to research from the Atlanta VA showing that veterans with early-stage non–small cell lung cancer who received housing and unemployment support had better overall survival, calling the finding “just as good as the drugs that we give.”

Disengagement from care linked to untreated mental illness was another focus. Tsao described a Dana-Farber Cancer Institute collaborative care model that flags patients with a serious mental illness diagnosis, such as schizophrenia or bipolar disorder, and connects them with a social worker and psychiatrist before they ever reach their first oncology appointment, rather than waiting for problems to surface in clinic.

“If you wait for [the patient] to walk in the door of the cancer center, you’re already behind, because tons of them don’t even make it to their first oncologist appointment,” she said.

Mazur said nurse coordinators can play a similar role by bundling scheduling for scans and specialist visits into a single trip, reducing the number of separate touchpoints that can overwhelm patients who are newly navigating the health system.

The panelists also weighed how much responsibility falls on the oncologists themselves for the financial burden that treatment creates. Azar said a running cost display in his institution’s electronic health record, showing the price of each order next to it, has made him more deliberate about what tests and scans he orders. Tsao then pointed to a Michigan collaborative care model, backed by Blue Cross Blue Shield, that embeds social workers and consulting psychiatrists directly into primary care and, increasingly, cancer clinics, as a rare example of a financial incentive aligning with better patient care.

Mazur said price transparency across health care, not just for individual drugs, will be needed to fully close the gap. “It might just take some time,” she said, “but we’ll get there.”

References

1. McCrear S. FDA approves fam-trastuzumab deruxtecan-nxki for metastatic HER2-positive breast cancer. AJMC. December 15, 2025. Accessed September 10, 2026. https://www.ajmc.com/view/fda-approved-fam-trastuzumab-deruxtecan-nxki-for-metastatic-her2-positive-breast-cancer

2. Hohmann E. FDA approves sacituzumab govitecan-hziy for first-line metastatic triple-negative breast cancer. AJMC. June 25, 2026. Accessed September 10, 2026. https://www.ajmc.com/view/fda-approves-sacituzumab-govitecan-hziy-for-first-line-metastatic-triple-negative-breast-cancer

3. Hohmann E. Datopotamab deruxtecan wins first-line FDA approval for immunotherapy-ineligible triple-negative breast cancer. AJMC. May 22, 2026. Accessed September 10, 2026. https://www.ajmc.com/view/datroway-wins-first-line-fda-approval-for-immunotherapy-ineligible-triple-negative-breast-cancer

4. Kelley MJ. VA National Precision Oncology Program. Fed Pract. 2020;37(suppl 4):S22-S27. doi:10.12788/fp.0037