immune checkpoint inhibitor

Study Compiling Outcomes of 17,000 Cancer Patients Highlights Need for Careful Treatment Planning, Monitoring

Adding immunotherapy to conventional treatment extends survival but is linked to increase in serious side effects

  • Largest study assessing impact of adding immunotherapy to conventional therapy
  • New study in Lancet Oncology documents increase in grade 3/4 adverse events
  • Findings highlight need for research into predictive biomarkers, risk factors

BUFFALO, N.Y. — Data from a multi-institutional research effort shed light on opportunities to improve the safety of adding immunotherapy to conventional curative therapies, underscoring the importance of close monitoring and multidisciplinary management. Led by a Roswell Park Comprehensive Cancer Center fellow, the work, newly published in The Lancet Oncology, demonstrates that the addition of immune checkpoint inhibition (ICI) to perioperative therapy was associated with increased treatment-related adverse events as well as an increasing trend of fatal toxicity.

The new work is the largest study to date to estimate the impact of adding immunotherapy to conventional perioperative systemic therapy. Lead author Yu Fujiwara, MD, a Hematology/Oncology Fellow at Roswell Park, notes that immune checkpoint blockade both before and after surgery remains an important treatment option for many patients with cancer. Dr. Fujiwara and colleagues including Senior Author Abdul Rafeh Naqash, MD, of Stephenson Cancer Center at the University of Oklahoma, initiated a meta-analysis analyzing the incidence of toxicity from immunotherapy before and/or after surgery in approximately 17,000 cancer patients.

“While recent studies have shown that the use of immune checkpoint blockade immunotherapy in the perioperative setting improved survival outcomes in patients with early-stage cancer, we saw a need for further safety evaluations of this approach,” says Dr. Fujiwara, who began the work during his internal medicine residency at the Icahn School of Medicine at Mount Sinai Beth Israel. “Our findings highlight the importance of good communication between patients and care teams both in treatment planning and during active treatment, and how critical it is for physicians to closely monitor for signs of potential adverse events in patients receiving checkpoint inhibitors.”

“The rate of fatal events with checkpoint inhibitors in the perioperative setting for early-stage cancer was 0.41%, closely mimicking the rate for fatal events for advanced/unresectable cancer 0.4-0.5% seen with single agent anti PD-1 inhibitors and lower than for combination of anti-CTLA4/PD-1, generally 1.0-1.2%. These findings underscore the importance careful patient selection and monitoring for these novel approaches,” notes Roswell Park Senior Vice President of Clinical Investigation and immunotherapy expert Igor Puzanov, MD, MSCI, FACP, who was not involved with this research.

A database search was conducted to identify studies assessing the use of immune checkpoint blockade alongside neoadjuvant/adjuvant therapy. Twenty-eight randomized-controlled trials, with a total of 16,976 patients, were included in the analysis. Of these studies, 19 were phase 3 and nine were phase 2. In regard to specific immunotherapies, the addition of CTLA-4, PD-1, and PD-L1 blockade was examined in seven, 10, and 11 clinical trials, respectively.

The addition of immune checkpoint blockade showed an increasing but not statistically significant increasing trend of grade 5 treatment-related deaths, and the authors report that this treatment approach increased grade 3-4 treatment-related adverse events and adverse events leading to treatment discontinuation, including fatal events in 0.41% of cases.

Findings from this study were consistent across different immune checkpoint blockade therapies with varying mechanisms of action (CTLA-4, PD-1 and PD-L1 blockade). Additionally, Dr. Fujiwara and colleagues found that the trends identified in this analysis were more prominent in studies with an ICI vs. placebo design, which was primarily used in the adjuvant treatment setting.

Given ongoing interest in neoadjuvant and adjuvant immune checkpoint blockade therapy, results from this analysis provide valuable safety information for future clinical trials. This data also emphasize the need for multidisciplinary management to ensure close monitoring of treatment-related adverse events as well as timely intervention by the appropriate clinicians.

Patient education is another key component of successful management of immune checkpoint inhibition therapy toxicity, note Dr. Fujiwara and colleagues, emphasizing that effective communication can help prevent treatment discontinuation and complications while potentially leading to improved outcomes and quality of life.

“Our analysis points to a need for further research into risk factors and identification of appropriate biomarkers to predict both efficacy and toxicity associated with cancer immunotherapy,” says Dr. Fujiwara.


From the world’s first chemotherapy research to the PSA prostate cancer biomarker, Roswell Park Comprehensive Cancer Center generates innovations that shape how cancer is detected, treated and prevented worldwide. Driven to eliminate cancer’s grip on humanity, the Roswell Park team of 4,000 makes compassionate, patient-centered cancer care and services accessible across New York State and beyond. Founded in 1898, Roswell Park was among the first three cancer centers nationwide to become a National Cancer Institute-designated comprehensive cancer center and is the only one to hold this designation in Upstate New York. To learn more about Roswell Park Comprehensive Cancer Center and the Roswell Park Care Network, visit, call 1-800-ROSWELL (1-800-767-9355) or email

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