Neoadjuvant immunotherapy may be effective prior to surgery in multiple types of cancers, according to a recent study published by Topalian et al in Cancer Cell.
Background
Neoadjuvant immune checkpoint blockades have been a rapidly growing area of research and are currently being tested across multiple tumor types in clinical trials—some of which have demonstrated that the treatments may produce pathologic complete responses in some settings. Although neoadjuvant immune checkpoint blockades are still largely experimental, there have been recent U.S. Food and Drug Administration approvals in triple-negative breast cancer and lung cancer.
Study Methods and Results
In the new study, investigators reviewed clinical trials examining the efficacy of immune checkpoint blockades in patients with lung cancer, triple-negative breast cancer, melanoma and nonmelanoma skin cancers, and gastrointestinal cancers that have established cross-cutting principles for this treatment approach.
The investigators noted that in patients with lung cancer, changes that happen in cancer tissue after immune checkpoint blockades may occur much more rapidly than what can be observed on computed tomography (CT) scans in standard oncology practice. In some cases, a tumor that may still be visible on CT scans contains no live tumor cells by the time of scheduled surgery. In the setting of neoadjuvant immune checkpoint blockades, pathologic response can tell researchers more about the treatment effects than radiographic response.
After analyzing immune checkpoint blockade trials in triple-negative breast cancer, the investigators found that a combination of chemotherapy plus immune checkpoint blockades can be effective at preventing postsurgical relapse and that administering immune checkpoint blockades in patients with earlier-stage cancer prior to surgery may be more effective than administering it in patients with advanced, inoperable disease. Further, in skin cancers, the investigators discovered that combination therapies may be helpful but not always needed and that some patients who have complete responses as seen under a microscope may not require extensive medical treatment. The investigators also revealed that patients with microsatellite instability–high gastrointestinal cancers may respond well to neoadjuvant immune checkpoint blockades and that some of them may not require surgery posttreatment.
Among other findings from the new study were:
- Immunotherapy regimens showing significant efficacy against advanced, inoperable tumors also tended to be effective when given prior to surgery.
- The degree of pathologic response after neoadjuvant immune checkpoint blockades may predict the relapse-free time interval after surgery.
- Neoadjuvant immune checkpoint blockades may not only prime antitumor activity in the immune system, but can also have a positive effect on surgery by either shrinking the tumors to the point where removing them may be less disfiguring or potentially making surgery unnecessary.
- Surgically removed tissue after neoadjuvant immune checkpoint blockades may offer a unique resource for in-depth scientific studies to learn more about how the treatment works and about how to overcome treatment resistance.
Conclusions
“We consider this approach to cancer immunotherapy to be a gold mine for advancing our scientific knowledge of how an immune checkpoint blockade is working, to define better biomarkers that predict clinical outcomes, and to help us design the next generation of more effective treatments with combination therapies,” concluded lead study author Suzanne Topalian, MD, Director of the Johns Hopkins Melanoma/Skin Cancer Program and Associate Director of the Bloomberg~Kimmel Institute for Cancer Immunotherapy.
Disclosure: For full disclosures of the study authors, visit sciencedirect.com.
