Ken Kato, MD, PhD, a medical oncologist at the National Cancer Center of Tokyo, and investigator in the pivotal CheckMate 648 study, underscores relevant safety data updates from the trial and important symptom management considerations with the FDA-approved combinations.
Nivolumab (Opdivo) in combination with fluoropyrimidine- and platinum-containing chemotherapy or ipilimumab (Yervoy) may become the new frontline standard of care for patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC), according to Ken Kato, MD, PhD.
Both combinations were recently approved by the FDA for adult patients, irrespective of PD-L1 status.1 The approvals were supported by findings from the global, randomized, open-label phase 3 CheckMate 648 trial (NCT03143153), in which 970 patients with unresectable advanced, recurrent, or metastatic ESCC were randomized 1:1:1 to receive nivolumab at 240 mg every 2 weeks plus fluorouracil and cisplatin every 4 weeks (n = 321), nivolumab at 3 mg/kg every 2 weeks plus ipilimumab at 1 mg/kg every 6 weeks (n = 325), or fluorouracil plus cisplatin every 4 weeks (n = 324).2
The findings demonstrated that patients who received either of the experimental combinations achieved superior overall survival (OS) compared with those who received chemotherapy alone. In the intention-to-treat population the median OS with the dual immunotherapy combination was 12.8 months (95% CI, 11.3-15.5) and 13.2 months (95% CI, 11.1-15.7) with the chemoimmunotherapy regimen. Compared with patients treated in the chemotherapy arm who had a median OS of 10.7 months (95% CI, 9.4-11.9), the reduction in risk of death was 22% (HR, 0.78; 95% CI, 0.65-0.95; P = .0110) and 26% (HR, 0.74; 95% CI, 0.61-0.90; P = .0021), respectively.1
In an interview with Oncology Nursing News®, Kato, a medical oncologist and chief of the Department of Esophageal, Head, and Neck Medical Oncology at the National Cancer Center Hospital in Tokyo, Japan, and an investigator in the CheckMate 648 trial, discusses safety data related to the combinations and what this means for prescribing nurses.
“The recent data from the Checkmate 648 Study shows a positive result for the first-round [treatment] with chemotherapy/nivolumab or nivolumab plus ipilimumab over chemotherapy alone,” Kato said. “[In my opinion,] these 2 treatments could become a new standard of care for the first line therapy for ESCC.”
Oncology Nursing News®: How did the safety profiles of the nivolumab-based combinations compare with one another?
Kato: IO [immune-oncology] combinations increase the [incidence of] irAEs [immune-related adverse effects] compared with IO monotherapy and chemotherapy/IO combination therapy. Endocrine [toxicities] were especially increased compared with the nivolumab/chemotherapy arm or nivolumab alone.3 For example, in the Checkmate 648, 27% of patients [n = 88] in the IO combination arm [experienced] any-grade endocrine toxicity and 6%  experienced grade 3 or 4 endocrine toxicity. On the other hand, only 12% [n = 36] of patients in the nivolumab/chemotherapy arm experienced this toxicity at any grade and only 1% [n = 4] of these patients experienced it severely. For chemotherapy alone, only 1% [n = 1] of patients experienced endocrine toxicities and no grade 3 or 4 [events] occurred.
At the recent 2022 ASCO [American Society of Clinical Oncology] Annual Meeting, Ian Chau, MD, reported on the timing of onset irAEs in this study. For example, with endocrine-related toxicities, the median onset time was 13.0 [range, 5.0 to 100.0] weeks with the nivolumab/chemotherapy combination. On the other hand, in the nivolumab/ipilimumab combination, the median onset time was 8.2 weeks [range, 1.9 to 72.9].
Skin toxicities were also reported in high proportion; 17% of patients [n = 54] experienced skin toxicities in the chemotherapy/nivolumab arm and 34% [n = 110] in the nivolumab/ipilimumab arm, compared with 4% [n = 11] in the chemotherapy arm.
Time-to-onset was [accelerated] in the IO arm and severity was increased. So, we should take care in the clinical practice whenever we prescribe this combination.
What are the key takeaways for oncology nurses?
I would emphasize that we should take care for [nonspecific] symptoms of the patient, because most often, irAEs do not have a specific symptom. For example, the initial symptom of the myocarditis is fatigue and of course, endocrine-related irAEs are the same: Fatigue is the first symptom. [Fatigue] contains the possibility [to be] many irAEs. We should take care as a community to communicate with the patient and their families.
If a patient has a change in symptoms, most of which are nonspecific symptoms, we can recommend they come to the clinic. Then we can [perform an] examination, for example, hormone doing, electrocardiogram, CT scan, or chest X-ray,[to] determine if an irAE is occurring. We should always check the nonspecific symptoms. It is very important.