medwireNews: Data from a pooled analysis of studies investigating first-line nivolumab plus ipilimumab has shown that, in line with the original trials, the combination is well tolerated by people with metastatic non-small-cell lung cancer (NSCLC).
Furthermore, “[s]afety was generally consistent regardless of age or histology, and treatment discontinuation due to TRAEs [treatment-related adverse events] had no negative effect on survival outcomes,” write Luis Paz-Ares (Universidad Complutense de Madrid, Spain) and co-authors in the Journal of Thoracic Oncology.
They reviewed data for 1255 individuals with metastatic NSCLC and no genomic driver alterations who took part in the CheckMate 227 Part 1, CheckMate 817 cohort A, or CheckMate 568 Part 1 studies of first-line nivolumab (3 mg/kg or 240 mg every 2 weeks) plus ipilimumab (1 mg/kg every 6 weeks).
During the trials, patients received a median of nine doses of nivolumab and three doses of ipilimumab. The median treatment duration was 4.1 months and the follow-up period was at least 31.0 months.
Overall, 77.8% experienced a TRAE of any grade between the first dose and 30 days after the last dose of study treatment, 34.3% had a grade 3 or 4 TRAE, and 23.2% had a serious AE, with 20.6% discontinuing either nivolumab or ipilimumab as a result of a TRAE.
Of note, the researchers found that the incidence of TRAEs was similar between patients with squamous and nonsquamous histology.
The most frequent TRAE was diarrhea, which occurred at any grade in 20.4% of participants and at grade 3 or 4 in 2.4%, followed by fatigue (17.5% and 1.8%, respectively), pruritus (16.7% and 0.6%), and rash (13.9% and 1.4%).
Immune-mediated AEs were generally grade 1 or 2 in severity, tended to occur within the first 6 months of treatment, and resolved with corticosteroids. The most common grade 3 or 4 immune-mediated AEs were hepatitis (4.9%), diarrhea or colitis (3.9%), and pneumonitis (3.9%).
There were 16 (1.3%) treatment-related deaths, of which 31.0% were a result of pneumonitis. The remaining causes of death included myocarditis, shock, autoimmune hepatitis, and pancreatitis, occurring in one patient each.
Paz-Ares and co-investigators also analyzed the data for the subgroup of 175 patients who were aged 75 years and older as “this patient population is generally underrepresented in cancer trials.”
They observed that the AE profiles largely reflected those in the overall population but the rate of grade 3 or 4 TRAEs was higher (43.7%) and discontinuation due to TRAEs was more common (29.3%). Two (1.1%) participants in this age group died as a result of treatment, one from myocarditis and one from autoimmune esophagitis.
Finally, the researchers report that “[d]iscontinuing nivolumab plus ipilimumab due to TRAEs did not negatively affect the long-term survival benefit observed in the overall pooled population.”
Indeed, the 3-year overall survival rate was 50% in the 225 patients who discontinued nivolumab plus ipilimumab due to TRAEs and 35% in the pooled population. Furthermore, 42% of 130 responders remained in response 2 years after discontinuation and 38% of patients did not receive subsequent systemic treatment for at least 2 years.
Paz-Ares et al conclude that the “large, pooled safety analysis of nivolumab plus ipilimumab demonstrates that this combination immunotherapy regimen provides a manageable safety and tolerability profile in patients with metastatic NSCLC, consistent with the individual studies.”
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