Getting Cancer Drugs To The Right Patients At The Right Time

Every advancement in cancer care — no matter how big or small — spurs optimism that we are moving closer to finding more effective treatments. Those advances are greatly needed since nearly 1.9 million new cancer cases are diagnosed annually in the United States alone.

Some of that optimism and innovation was on full display at the American Society of Clinical Oncology’s annual meeting in Chicago. The conference, which draws close to 40,000 attendees, brings together clinicians, drugmakers, policymakers, and researchers to share ways for improving cancer care and to unveil discoveries.

The theme of this year’s meeting was “Partnering with Patients: The Cornerstone of Cancer Care and Research.” We heard a lot of conversations along those lines during our time at ASCO. There was also a heavy emphasis on closing the health equity gap. Below are three areas that stood out to us as important markers for industry leaders.

Antibody-drug Conjugates — A Rising Wave in Solid Tumor Oncology

Although they’ve been around for nearly 20 years, ADCs are moving into the spotlight. The treatment, which essentially allows cancer-killing drugs to be targeted directly at a tumor, was a major focus during this year’s conference. We heard about several novel targets in both early- and late-stage development.

But as companies flesh out their investment strategies, they must consider the capabilities required to thrive in rapidly evolving marketing. We identified three themes as the field continues to explore how to best leverage these drugs and determine which patient populations are most likely to benefit from the treatment:

• Target expression matters: Although patients require less expression to see results from ADCs, higher target expression is often associated with greater benefits. This relationship appears to be heterogenous across tumor types, even for the same antigen target.
• Diverse resistance pathways: Understanding why cells develop resistance, whether to the antibody or the linker/payload, is critical for developing novel therapies and determining sequencing strategies. While little is known today, early experience indicates that there is high heterogeneity across patients.
• Future design concepts: The first clinical data of a bispecific antibody-drug conjugate was presented at ASCO this year, heralding the next wave of potential constructs. Novel payloads and combination strategies were also discussed as potential ways to improve outcomes with ADCs. 

The Race Between CAR-T and Bispecific Antibodies in Hematological Malignancies

Advances with CAR-T and bispecific antibody therapy are revolutionizing the hematological malignancy landscape, with the possibility of a cure in earlier lines of therapy on the horizon. The landscapes, overall, are becoming crowded with multiple product choices and combination regimens that must be weighed against underlying patient characteristics. As these therapies move into earlier lines of therapy, physicians are faced with the difficult challenges of selecting which drug or drug combinations are right for which patients and then how to sequence them once the disease progresses.

The opportunities and challenges for both were hot topics at ASCO. Looking at CAR-T, Surbhi Sidana, MD, from Stanford University School of Medicine, highlighted some key considerations, including access to care. The ability to take advantage of CAR-T is often hampered by the limited number of centers providing treatment, racial and socioeconomic inequities, and unknown outcomes in patients with common comorbidities. All of these perpetuate health disparities. The complexity of CAR-T manufacturing also leads to a long vein-to-vein time — the time from collection of T cells to CAR-T infusion. In one study, this resulted in only 29% of patients receiving therapy by 12 months and 32% of patients dying in the first year while awaiting therapy. Safety is also a factor, including cytokine release syndrome, severe neutropenia, and neurotoxicity. These side effects can be ameliorated with prophylactic supportive care but they add to the complexity, inconvenience, and overall cost of care.

While Bispecific antibody therapies are pushing survival rates to new levels in hematological malignancies, they also face challenges. Bispecifics cause some side effects but they have the advantage of being off the shelf and more readily accessible to physicians and patients. Although head-to-head studies versus CART are not available, it is anticipated that bispecific antibodies with similar mechanistic targets as CAR-T counterparts will have efficacy approaching, but not at the levels of CAR-T. These agents often have more favorable safety profiles but require consistent infusions with a provider instead of a one-time therapy such as CAR-T.

Embracing Change in Clinical Trials

The current system governing clinical trials is highly burdensome on participating patients, investigators, and research staff. It’s too slow, and, as our colleagues noted in this Oliver Wyman Health piece, exacerbates health inequities, with clinical trials inaccessible for most patients with cancer.

Simplifying protocols and lowering enrollment criteria when possible, such as with the PRAGMATICA-Lung study, are an essential path forward, as is the continued deployment of hybrid or decentralized clinical trials to decrease patient burden. It’s “critical to step back and ask what are the essential questions that the clinical trial is intended to answer and determine the most efficient way to do that,” Richard Pazdur, MD, Director of the Food and Drug Administration’s Oncology Center of Excellence remarked during a panel discussion.

There isn’t a one-size-fits-all approach, so biopharmaceutical manufacturers need to think about when and how to embrace innovative clinical trial models. Which programs are good candidates to be (partially) decentralized? What new capabilities or partnerships are necessary to enable these models? How can organizations mitigate the risks of change while doing right by patients?

We’ll dig deeper into innovation in oncology in future Oliver Wyman Health articles.

To learn more contact Matthew Weinstock, Senior Editor, Health and Life Sciences.