Real-World Study Confirms Nivolumab Plus Ipilimumab Safety in Advanced NSCLC


A real-world study confirmed that the rate of adverse events associated with first-line nivolumab plus iplimumab therapy was in line with the safety profiles of other immuno-oncology and chemotherapy combination regimens.

A real-world study among patients with advanced non–small cell lung cancer (NSCLC), found that the safety of first-line (1L) nivolumab plus iplimumab (NIVO + IPI) therapy was similar to that of other approved combination therapies involving an immuno-oncology (IO) agent and chemotherapy.

The retrospective, observational analysis, published in Future Oncology, sought to clarify the safety profile of 1L NIVO + IPI because although the regimen has been declared as safe by the FDA, some patients still experience adverse events. Additionally, there is limited information on the side effects of this treatment in real-world settings.

cancer cells | Image credit: Sodapeaw -

Image credit: Sodapeaw -

Researchers collected data from the Flatiron Health database, which only goes up to October 2021. The database included health record and unstructured data from physicians’ notes and other documents. Patients were eligible for inclusion if they were recorded in the advanced NSCLC Core Registry on or after January 1, 2011 and received 1 of the following 1L therapies before April 30, 2021:

  • Cohort 1: NIVO + IPI
  • Cohort 2: NIVO + IPI plus chemotherapy
  • Cohort 3: another approved IO agent plus chemotherapy

Overall, 262 patients were enrolled (cohort 1, n = 137; cohort 2, n = 46; cohort 3, n = 79). Patients from cohorts 1 and 2 were included in the Flatiron Health database, whereas the cohort 3 patients were randomly selected from all eligible patients receiving other approved IO agents plus chemotherapy. The mean (SD) ages for each cohort were 71.4 (9.9), 68.8 (9.4), 68.7 (8.5), respectively. Men comprised the majority of all cohorts (female, 46.7% vs 391% vs 45.6%), and most patients were White (72.3% vs 60.9% vs 72.2%).

Across cohorts, most patients were diagnosed with stage IV disease, exhibited an Eastern Cooperative Oncology Group performance status of 0 or 1, and had non-squamous NSCLC. Moreover, when comparing cohorts 1 and 2 vs cohort 3, a similar proportion of patients had tumor PD-L1 expression levels below 1% (29.2% vs 35.4%), had levels between 1% and 49% (38.7% vs 29.1%), had levels of 50% or higher (17.5% vs 13.9%), and had unknown tumor PD-L1 expression levels (14.6% vs 21.5%). The median (IQR) treatment duration was 3.7 (1.3-8.5) months for cohorts 1 and 2 and 3.0 (2.8-4.3) for cohort 3.

The most common adverse events among those receiving NIVO +IPI were fatigue (67.9%), pain (66.4%), dyspnea (47.4%), weight loss (43.8%), decreased appetite (40.1%), diarrhea (38.7%), nausea/vomiting (35.8%), cough (35.0%), constipation (32.1%), and rash (29.9%). Additionally, 17.5% of patients receiving this therapy experienced lung infections during treatment.

Most patients in cohorts 1 and 2 who experienced adverse events received treatment to manage them, including 26.3% of patients who required hospitalization, 24.8% who held therapy due to adverse events, 4.4% who requested dose or schedule changes, and 9.5% who discontinued treatment.

Among the patients in cohort 3, the most common adverse events were fatigue (77.2%), pain (60.8%), nausea/vomiting (51.9%), decreased appetite (45.6%), constipation (45.6%), weight loss (44.3%), dyspnea (43.0%), cough (43.0%), diarrhea (36.7%), rash (29.1%), and peripheral edema (29.1%). Another 15.2% encountered lung infections.

Nearly all the patients in cohort 3 who experienced and adverse event (96.2%) received treatment to manage them. Overall, 25.3% of patients experienced AEs that led to hospitalization, 30.4% required therapy hold due to AE, 12.7% experienced therapy dose or schedule change, and 16.5% discontinued therapy.

The authors noted that the similar rates of hospitalization suggested similar clinical and economic burdens between cohorts.

The study had some limitations, including focusing solely on first-line therapy for assessing adverse events, lacking grading data, and having small sample sizes across cohorts. The authors cautioned against comparing safety data due to descriptive analysis and highlighted the possibility of overlooking other clinically significant adverse events such as anemia and hepatitis within its predefined scope.


Betts KA, Gao S, Ray S, Schoenfeld AJ. Real-world safety of first-line immuno-oncology combination therapies for advanced non-small-cell lung cancer. Future Oncol. Published online January 19, 2024. doi:10.2217/fon-2023-0612

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