First-line sintilimab combination improves PFS in non-small cell lung cancer subset
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Adding sintilimab to gemcitabine and platinum improved PFS as first-line treatment for patients with locally advanced or metastatic squamous non-small cell lung cancer, according to a study published in Journal of Thoracic Oncology.
The combination also had an acceptable toxicity profile, results of the randomized, double-blind, phase 3 ORIENT-12 trial showed.
“In this study, the risk [for] disease progression or death was reduced by 37.9% at interim analysis and by 46.4% at updated analysis. The results from ORIENT-12 could provide a new option for combination therapy in this patient population,” Caicun Zhou, MD, PhD, director of the department of oncology at Shanghai Pulmonary Hospital in China, said in a press release.
Zhou and colleagues evaluated the efficacy and safety of sintilimab (Tyvyt; Eli Lilly, Innovent Biologics), an anti-PD-1 antibody, in combination with gemcitabine and platinum, a standard chemotherapy regimen for squamous NSCLC, because it had shown efficacy as first-line treatment in a phase 1b study.
Researchers screened 543 patients with locally advanced or metastatic squamous NSCLC and without EGFR-sensitive mutations or ALK rearrangements at 42 centers in China between Sept. 25, 2018, and July 26, 2019. They randomly assigned 357 of those patients 1:1 to either 200 mg sintilimab (n = 179) or placebo (n = 178) every 3 weeks in combination with 1 g/m2 IV gemcitabine on days 1 and 8 and either 75 mg/m2 IV cisplatin on day 1 or IV carboplatin area under the concentration-time curve 5 mg/mL/min on day 1 every 3 weeks for four to six cycles, as determined by investigator. Following the combination treatment, patients received 200 mg sintilimab or placebo as maintenance therapy every 3 weeks for up to 24 months until disease progression, intolerable toxicity or withdrawal of consent.
The sintilimab and placebo groups had similar baseline characteristics, including median patient age (64 years vs. 62 years) and percentages of men (91.1% vs. 92.1%), those with an ECOG performance status of 1 (83.2% vs. 87.6%) and those with stage IV disease (78.2% vs. 75.3%).
PFS according to independent radiographic review committee served as the primary endpoint.
Median follow-up was 12.9 months (range, 0.5-17.9) at the data cutoff on March 25, 2020.
Results showed 127 patients (70.9%) in the sintilimab group and 165 (92.7%) in the placebo group either experienced disease progression or died.
Researchers reported “meaningful improvement” in PFS with sintilimab vs. placebo (median, 5.5 months vs. 4.9 months; HR = 0.536, 95% CI, 0.422-0.681).
At 12 months, the PFS rate was 22.3% (95% CI, 16-29.4) with the sintilimab regimen and 3.1% (95% CI, 1.2-6.7) with the placebo regimen. The confirmed objective response rate also was higher with sintilimab (44.7%; 95% CI, 37.3-52.3) vs. placebo (35.4%; 95% CI, 28.4-42.9).
OS data were immature at the time of the updated analysis.
A higher percentage of patients in the sintilimab group experienced grade 3 or higher treatment-emergent adverse events (86.6% vs. 83.1%), whereas a higher percentage in the placebo group had adverse events that led to treatment discontinuation (16.3% vs. 14.5%) or death (6.7% vs. 4.5%).
The most common grade 3 or higher treatment-related adverse events in the sintilimab vs. placebo group included decreased neutrophil count (48.6% vs. 47.8%), decreased platelet count (45.3% vs. 42.7%), decreased white blood cell count (36.3% vs. 36.5%) and anemia (33.5% vs. 32%).
“The results of the ORIENT-12 study add to the growing body of data regarding the addition of anti-PD-1/PD-L1 treatment to first-line chemotherapy in squamous NSCLC,” Zhou and colleagues wrote. “[The study] demonstrated that the addition of sintilimab to standard chemotherapy with gemcitabine and platinum could significantly prolong the PFS in patients with previously untreated advanced or metastatic squamous NSCLC, with manageable safety profiles.”
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