Addition of immunotherapy to perioperative cancer treatment linked to more toxicity
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The addition of immunotherapy to perioperative conventional cancer therapy appeared linked to more grade 3 to grade 4 treatment related adverse events, according to findings published in The Lancet Oncology.
“Our study emphasizes the importance of safety evaluation among patients receiving immunotherapy before or after the curative treatment, which is usually surgery,” Yu Fujiwara, MD, a hematology/oncology fellow at Roswell Park Comprehensive Cancer Center, told Healio.
The use of immune checkpoint blockade as part of perioperative cancer therapy has improved outcomes; however, questions remained about the safety of this approach.
“These patients receive perioperative treatment with curative intent and are expected to live longer,” Fujiwara said. “Thus, we performed our study to accurately evaluate the impact of adding immunotherapy to conventional perioperative therapy on treatment-related adverse events, including fatal toxicity.”
Fujiwara and colleagues conducted a systematic review and meta-analysis of 28 randomized controlled trials with a combined 16,976 patients.
Researchers aimed to determine whether adding immune checkpoint blockade therapies that target CTLA-4, PD-1 or PD-L1 to perioperative therapy affected treatment-related adverse events.
Results showed the addition of immune checkpoint blockade increased incidence of grade 3 or grade 4 treatment-related adverse events (OR = 2.73; 95% CI, 1.98-3.76), any-grade treatment-related adverse events (OR = 2.6; 95% CI, 1.88-3.61) and adverse events that led to treatment discontinuation (OR = 3.67; 95% CI, 2.45-5.51).
However, the addition of immune checkpoint blockade did not appear linked to increased risk for treatment-related death (OR = 1.76; 95% CI, 0.95-3.25). Researchers identified 40 fatal toxicities among 9,864 patients treated with immune checkpoint blockade, with pneumonitis accounting for six (15%) of them.
Healio spoke with Fujiwara and senior study author Abdul Rafeh Naqash, MD, of Stephenson Cancer Center at University of Oklahoma, about the findings, their potential implications, and how oncologists can strive to ensure the safety of patients receiving immunotherapy as part of perioperative treatment regimens. Their joint responses appear below.
Healio: How did you conduct this study?
Fujiwara/Naqash: To ensure the quality of our research, we first identified all published articles reporting the incidence of treatment-related death and safety outcomes of randomized clinical trials, and then pooled the number of these outcomes. Upon conducting this study, we built a multi-institutional team with experts in the immunotherapy field and statistical analysis.
Healio: What did you find?
Fujiwara/Naqash: The major findings of our study are that the addition of perioperative immunotherapy to conventional treatment — adjuvant and/or neoadjuvant — increased the incidence of grade 3 to grade 4 treatment-related adverse events and adverse events leading to treatment discontinuation, but it did not statistically increase the incidence of treatment-related deaths. These findings were consistent across different types of immunotherapy and were more observed in studies evaluating immunotherapy in the adjuvant setting.
Healio: Do these findings indicate a need to better monitor potential adverse events among patients receiving perioperative immune checkpoint blockade?
Fujiwara/Naqash: Our study suggests that we should not underestimate the impact of immunotherapy on the incidence of adverse events and indicates a need to closely monitor adverse events. Our study was conducted by pooling data from randomized clinical trials, of which usually the observation periods are limited. Thus, long-term follow-up safety data in these clinical trials or from real-world data are needed to better understand how we should follow patients after they finish perioperative immunotherapy.
Healio: What can oncologists do to better serve these patients?
Fujiwara/Naqash: Symptoms of immunotherapy-related adverse events are often nonspecific. Consequently, oncologists need to establish better communication with patients so patients can easily mention any symptoms they may have during immunotherapy to oncologists. Oncologists should address these symptoms by performing laboratory work, which ensures early interventions for adverse events.
Reference:
For more information:
Yu Fujiwara, MD, can be reached at Roswell Park Comprehensive Cancer Center, 665 Elm St., Buffalo, NY 14203.
Abdul Rafeh Naqash, MD, can be reached at Medical Oncology/TSET Phase 1 Program, Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK 73104; email: abdulrafeh-naqash@ouhsc.edu.
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