Remarkable Outcomes With Cancer Immunotherapy, but Clinical Adoption Remains Challenging

The cancer community has seen tremendous progress in the field of immunotherapy. However, educating patients and care providers across healthcare on this new tool remains a significant challenge. This was a common thought echoed by panelists at the Institute for Clinical Immuno-Oncology National Conference on September 30, 2016, as they discussed real-time adoption of immunotherapy. The meeting was organized by the Association of Community Cancer Centers in Philadelphia.

Academic center and community perspectives were outlined by 3 oncologists—Lee Schwartzberg, MD, FACP, from West Clinic and the University of Tennessee; Tara Gangadhar, MD, from the Abramson Cancer Center at the University of Pennsylvania; and Jose Lutzky, MD, FACP, from the Mount Sinai Medical Center Comprehensive Cancer Center.

Schwartzberg said that the cancer center at West Clinic has seen a significant increase in the number of patients receiving immuno-oncology (IO) agents—from 2 in 2014 to 306 patients in 2016 so far. “A majority of the treatments have been in patients diagnosed with non-small cell lung cancer,” he said. Statistics from their clinic documented 20% of patients were being treated with programmed death-1 (PD-1) inhibitors for indications yet to receive clinical approval, including for gynecological cancers; tumors of the central nervous system, thymus, and breast; and lymphoma.

“Community clinicians are paying attention to recent progress in the field,” Schwartzberg told the audience, adding that recent development has been remarkable, including the fact that the annual meeting of the American Society of Clinical Oncology saw 150 abstracts on checkpoint inhibitors alone.

However, providers across the spectrum of need to be aware of not just adverse effects such as cytotoxicity and immune-related adverse events (irAEs), but also pseudoprogression, Schwartzberg emphasized. “We are of course interested in biomarkers of response because we need to increase the percentage of responders,” he said, pointing out that, currently, the only known biomarkers being used in the clinic are programmed death-ligand 1 (PD-L1), total tumor burden, and mismatch repair-deficient high.

“Patient access is critical and there’s no referring it away,” Schwartzberg said. “Typically, with new treatments, patients are usually treated at the academic centers and then the treatment trickles into the clinic. IOs, however, have reached the clinics very quickly.”

The main concerns among payers as well as providers, however, is the affordability of these treatments. Combination therapy with 2 IO agents such as iplimumab and nivolumab could cost several hundred thousand annually. “What would be the value proposition of this treatment? Would it be the [quality-adjusted life years] or the impact of the treatment on the tail of the survival curve?” Schwartzberg asked.

Addressing IO Toxicity—What Do Patients Need?

Gangadhar focused her attention on managing the toxicity of these agents. Patients on IO need 24/7 access to providers, she said, adding that irAEs should be considered in the differential of any new symptom for any organ system that patients on IO agents might present with at the emergency room or clinic.

“It’s also important that patients are assessed for toxicity prior to each treatment—either by the primary care physician (PCP) or the oncologist,” Gangadhar said.

Gangadhar listed the following as the most common irAEs observed with PD-1 inhibitors:

• Pruritis/rash: which can be managed with antihistamines or over-the-counter steroids
• Arthralgia: can be controlled with non-steroidal anti-inflammatory agents
• Diarrhea
• Elevated AST/ALT (indicators of liver damage)

Some of the more uncommon adverse effects observed are aseptic meningitis, acute kidney injury, uveitis, and pancreatitis, Gangadhar said.

For toxicity management, “communication and reporting are very important. Increasing the frequency of phone check-ins and office visits can help monitor the patients better,” she said.

In Gangadhar’s clinic, atypical response has been documented in only 6% of patients in her clinic who are on pembrolizumab, while higher rates have been seen with ipilimumab.

Lutzky suggested that dual response criteria, such as RECIST and immune-relate response criteria used by radiologists, should be adapted to monitor patients on IO agents. “Additional imaging tests may be needed to confirm progression or delayed response to treatment,” he said.

According to Lutzky, education on patient reaction to treatment with IO should cross the boundaries of cancer centers and be provided to PCPs, emergency department and intensive care unit personnel, surgeons, and house staff. He echoed Gangadhar’s sentiments on close monitoring of patients, with calls by resident nurses as well as educating patients on what to expect and asking them to call in with any unusual health concerns.

All these services are an added cost to the system, not just the price of these agents alone. The amount of analysis on the pathology laboratory alone—such as immunohistochemistry of tumor infiltrates, mutation load, and new predictive tests—would significantly increase the cost of care.

Lutzky ended his presentation by highlighting some of the current financial challenges with the use of IO agents:

• Insurance coverage and authorization: choosing between FDA approval, National Comprehensive Cancer Network guidelines, and phase 3 data.
• Drug replacement plans: they can delay treatment, especially with high copays, because drugs are not delivered until the copay is cleared.
• Imaging and laboratory studies reimbursement needs third-party payer education

Adding another level of complexity are patients who are uninsured, off-label use of these agents that could be challenged by insurers, high annual deductibles, and patients who may be considered too rich to get financial assistance, Lutzky said.