Access and Disparity Questions Around Rilvegostomig+T-DXd: Coral Omene, MD, PhD

With nearly two-thirds of responding patients in the I-SPY 2.2 trial spared traditional chemotherapy and nearly all avoiding anthracyclines, the combination of rilvegostomig (R) and trastuzumab deruxtecan (T-DXd) raises pressing questions about toxicity tradeoffs, cost, and coverage in a drug class already known for high price tags, said Coral Omene, MD, PhD, program director of breast cancer disparities research and associate professor of medicine at Robert Wood Johnson Medical School, Division of Medical Oncology, Rutgers Cancer Institute.

It also raises questions about whether the patients most likely to benefit, including Black women with triple-negative breast cancer (TNBC), will actually have access to this approach if it reaches approval. Omene addresses these dimensions, drawing on her research in health disparities and her direct experience counseling patients through complex treatment decisions.

In part 1 of this conversation with The American Journal of Managed Care^® (AJMC^®), Omene discussed the efficacy results of the I-SPY 2.2 trial.

This transcript has been lightly edited for clarity.

AJMC: 64% of patients who responded to pCR skipped traditional chemotherapy entirely, and 97% avoided anthracyclines. For patients and oncologists, what does that mean in practice, and how do you counsel a patient about accepting the risks of this regimen in exchange for potentially skipping chemo?

Omene: For a long time now, in oncology, we have been focused on de-escalating treatment as much as possible while achieving similar or superior efficacy. One of the important goals has been trying to minimize the use of chemotherapy. In this instance, the majority of patients were spared unnecessary chemotherapy, including an anthracycline-containing regimen, which carries long-term risks for cardiotoxicity and leukemias. Comparing side effects between R + T-DXd (Block A and all blocks) vs control, there were similar rates of constipation, nausea, and fatigue, and lower rates of neutropenia, anemia, musculoskeletal pain, peripheral neuropathy, and rash were observed with the combination. It is true that the tradeoff would be the risk of interstitial lung disease (ILD), but the trial implemented real-time monitoring strategies with CT chest every 6 weeks being the most effective at detection of ILD. There are guidelines for treating ILD once suspected or detected. It was further reassuring that all the ILD events were mostly low grade and all patients recovered without recurrences.

AJMC: T-DXd is already approved for HER2-low metastatic breast cancer, and rilvegostomig is in multiple trials. If this combination moves forward toward approval in the neoadjuvant setting, what does the cost and access picture look like, particularly when the counterargument is that avoiding chemotherapy may offset some of that cost?

Omene: Unfortunately, the cost of drugs in oncology remains very high, and that is something that needs to be addressed urgently in our health care system, from policy changes to manufacturing to insurance coverage. While for some there may be strong commercial coverage and meaningful copay assistance program support, significant barriers for uninsured, Medicaid, and Medicare patients remain.

Broadly, we know the cost of antibody-drug conjugates and immunotherapy are expensive, but some of the costs may be offset by the avoidance of chemotherapy and associated side effects. For instance, the trial found that compared with controls, the R/T-DXd regimen showed decreased rates of neutropenia. Lower neutropenia rates particularly matter as we use granulocyte-colony stimulating factor (G-CSF) prophylaxis (filgrastim/pegfilgrastim) to correct this for patients and can add $3000 to $8000 per cycle. Hospitalizations for febrile neutropenia average $20,000 to $30,000 per episode, so reducing this is important both for the patient’s health as well as cost-wise.

AJMC: Your research has a strong focus on health disparities and TNBC, which disproportionately affects Black women. The immune-positive TNBC subtype was one of the groups that responded well here. How do you think about ensuring that the patients who stand to benefit most from a combination like this are actually represented in the trials and ultimately in the clinical rollout?

Omene: This is a question where the science and the health system infrastructure all must work simultaneously to improve diversity in trials and where we still have a lot of work to do in oncology. These patients who stand to benefit most have been systematically underrepresented in oncology trials for decades, face greater socioeconomic barriers to trial participation, and live in geographic areas with fewer academic medical centers running this kind of adaptive platform trial.

The solution is multifactorial and should include a concerted effort for outreach to these patients and education regarding the benefits of clinical trials. In trial design, there should be realistic diversity plans with enrollment targets. In this instance, pre-specifying that immune-positive TNBC in minority populations is a primary subgroup of interest, with minimum enrollment floors, not aspirational percentages, would be helpful. The trial infrastructure should be made available to community oncology settings or creating deliberate satellite enrollment models where community oncologists can refer and co-manage.

This is something that the I-SPY 2 trials have managed to do well in their partnering efforts for their trials. Biomarker assay access as a parallel workstream, not waiting for approval to figure out who gets tested and how it's reimbursed. Financial cost can be significant, and assistance should be embedded in a meaningful way in the trial. Even when minority patients enroll, they disproportionately drop out due to costs that trials don't cover: transportation, childcare, lost wages for trial visits, and lodging for patients traveling distances. The dropouts directly affect the data as it produces efficacy estimates that don't generalize to those patients anyway.