Study Raises Clinical Considerations for Strategic Immunotherapy Use in Metastatic Cancer Care

Clinical Relevance: Increasing late-stage immunotherapy use necessitates careful consideration of timing and setting by physicians to maximize patient outcomes and survival.

__________________________________________________________________________________________________________The Yale School of Medicine has conducted a study highlighting the benefits of immunotherapy in treating certain late-stage cancer patients. This research underscores the importance of timing and setting in administering immunotherapy, as these factors significantly affect patient survival. Oncologists should carefully evaluate the appropriateness of this treatment for each patient, considering its potential to improve outcomes.

The national cohort study of 242,371 patients with stage IV melanoma, non-small cell lung cancer (NSCLC), or kidney cell carcinoma, the initiation of immunotherapy within one month of death significantly increased from 0.8% to 4.3% for melanoma, 0.9% to 3.2% for NSCLC, and 0.5% to 2.6% for kidney cell carcinoma from the initial approval dates through December 2019. 

By 2019, these late immunotherapy initiations accounted for 7.3% of all immunotherapy treatments. Patients with three or more organs involved in metastatic disease were 3.8 times more likely to die within one month of immunotherapy initiation compared to those with only lymph node involvement. 

The study also found that within the last decade, the number of metastatic cancer patients being given immunotherapy in the last month of their life has “significantly increased…accounting for one in 14 immunotherapy treatments overall.”

This trend underscores the growing use of end-of-life immunotherapy and highlights the need for further research on its benefits and value in advanced-stage disease.

Dr. Sajid Khan is the lead author of the JAMA Oncology study. He is also the section chief of Hepato-Pancreato-Biliary (HPB) and Mixed Tumors at Yale School of Medicine. He tells SurvivorNet that “immunotherapy is not effective for many patients with early-stage disease.” 

Hence, this contributed to metastatic cancer patients diagnosed with melanoma, non-small cell lung cancer, and kidney cancer being chosen for the study.

He adds that surgery is the mainstay treatment for these types of cancer patients in the early stages of their cancer.

“Immunotherapy is sometimes administered in an adjuvant (post-operative) setting. However, in metastatic cancers, immunotherapy is highly effective for treating melanoma, non-small cell lung cancer, and kidney cell cancer,” Dr. Khan added.

Related: Why Immunotherapy Doesn’t Work for Every Patient

Location, location, location

The study also suggests that treatment in academic or high-volume centers was associated with a 30-31% decrease in the odds of death within a month of starting immunotherapy. 

“Low-volume and non-academic hospitals have worse survival for immunotherapy as a whole, plus are more likely to have patients immunotherapy initiated within the last 30 days of life,” Dr. Khan explained.

He believes these facilities are “less resourced than high volume and academic hospitals,” which could be contributing factors to the poorer survival outcomes.

Academic centers and community centers both offer standard-of-care treatment for various cancers. However, academic centers may have more access to certain treatments in the clinical trial phase.

Standard care refers to delivering the appropriate treatment by standards formed based on current medical literature and national guidelines.

Academic cancer centers might have better access to ongoing clinical trials, but clinical trials differ from standard-of-care. Clinical trials seek to explore the effects of a new medication or compare new treatments to the current standard of care.

Additionally, there is a significant amount of variability between academic and community centers, making it difficult to make broad claims comparing the different cancer centers.

“In terms of access to standard care, be it chemotherapy, targeted therapy, or immunotherapy, all those approved drugs are available for use regardless of where you get treatment or care,” Dr. Chul Kim, a medical oncologist at MedStar Health in Washington, D.C. explained to SurvivorNet.

Despite the findings showing an advantage to treatment at a larger institution, the researchers say more research is still needed.

Related: New Cancer Treatments Like Immunotherapy Have Helped Prevent More Than 4 Million of Deaths From Cancer 

Immunotherapy Advancements

Immunotherapy represents a transformative approach in cancer treatment, leveraging the body’s immune system to recognize and combat cancer cells. 

Unlike traditional treatments such as chemotherapy and radiation, which directly target cancer cells but can also harm normal cells, immunotherapy works by enhancing or restoring the immune system’s inherent ability to fight cancer. 

This is achieved through various strategies, including checkpoint inhibitors that block proteins used by cancer cells to evade immune detection, cancer vaccines that stimulate the immune system to attack specific cancer antigens, and adoptive cell therapies like CAR T-cell therapy, which involves modifying a patient’s T cells to better target cancer cells.

For physicians, understanding the mechanisms of action, the potential for combination with other treatments, and the unique side effect profiles of immunotherapies is crucial. 

Checkpoint inhibitors, for example, target PD-1, PD-L1, and CTLA-4 pathways, integral checkpoints in immune regulation, to prevent cancer cells from inhibiting immune responses. 

This can lead to durable responses in various cancers, including melanoma, NSCLC, and kidney cancer. However, these treatments can also cause immune-related adverse events (irAEs) due to the activation of the immune system against normal tissues, requiring vigilance for symptoms and prompt management. 

However, immunotherapy doesn’t work for everyone with cancer. Dr. Vamsidhar Velcheti, the director of thoracic oncology at NYU Perlmutter Cancer Center, says that, unfortunately, it’s still difficult to predict which patients will respond well.

“The ways cancer generally escapes the body’s immune system is by protecting itself by producing certain proteins,” said Dr. Velcheti. “PD-L1 is one of those proteins that actually helps protect the cancer from the body’s immune system. For patients with high levels of PD-L1, you could potentially use single-agent immunotherapy with good outcomes. The problem is that these proteins are constantly in flux.”

Watch: Nobel Prize Winer, Dr. Jim Allison Discusses the Evolution of Immunotherapy