New results from ORIENT-31 show a sustained progression-free survival benefit and overall survival improvement trend in patients with EGFR-mutant non–small cell lung cancer who failed a tyrosine kinase inhibitor previously.
Statistically significant and clinically meaningful improvement in progression-free survival (PFS) have been demonstrated with sintilimab (Tyvyt) plus bevacizumab (Avastin) combined with pemetrexed and cisplatin in patients with EGFR-mutated, non-squamous non–small cell lung cancer (NSCLC), who progressed after treatment with an EGFR tyrosine kinase inhibitor (TKI).1
“ORIENT-31 is globally the first prospective, randomized, double-blind phase 3 study that demonstrated significant PFS benefit of combination therapy of anti-PD-1 antibody and chemotherapy with or without bevacizumab in patients with EGFR-mutated non-squamous NSCLC that progressed on prior EGFR-TKI therapy, which was revolutionary in immunotherapy,” said Shun Lu, MD, PhD, professor of the Oncology Department of Shanghai Chest Hospital, in a press release. “I am pleased to witness the first and second interim analysis results of the ORIENT-31 study were published in international authoritative and influential journals. Besides, I hope that the recent approval of sintilimab in combination with bevacizumab and chemotherapy in treatment of patients with EGFR-mutated non-squamous NSCLC that progressed on prior EGFR-TKI therapy can bring a new treatment option benefiting more patients [with cancer].”
Results comes from the second interim analysis of the phase 3 ORIENT-31 clinical trial (NCT03802240). All patients in the study were Chinese patients between the ages of 18 years and 75 years. Patients had a histologically or cytologically confirmed diagnosis of EGFR-mutant NSCLC, were previously treated with an EGFR TKI, and had measurable disease. Patients received sintilimab 200 mg via intravenous (IV) infusion every 3 weeks (Q3W) with bevacizumab 15 mg/kg IV Q3W, pemetrexed 500mg/m2 IV Q3W, and cisplatin 75 mg/m2 IV Q3W, or matching chemotherapy.1,2
As of the data cutoff date of March 31, 2022, and with a median follow-up of 12.9 months in the sintilimab arm (arm A) and 14.4 months in the chemotherapy arm (arm C), the median PFS was 7.2 months (95% CI, 6.6-9.3 months) vs 5.5 months (95% CI, 4.5-6.1 months), respectively (HR, 0.72; 95% CI, 0.55-0.94, P = .01). With this result, sintilimab plus bevacizumab and chemotherapy crossed the pre-specified boundary for superiority. Compared with data previously published from arm A of the study, the PFS benefit of the sintilimab combination was sustained (HR, 0.51; 95% CI, 0.39-0.67; P < .0001).1
The median overall survival (OS) in the sintilimab arm was 21.1 months vs 19.2 months with chemotherapy alone (HR, 0.98). The OS analysis included patients who crossed over to arm A. The HR for OS ranged from 0.79 to 0.84 and signaled an OS improvement trend.
Safety findings from the second interim analysis were consistent with the first interim analysis, as well previously reported studies of sintilimab plus bevacizumab. No new safety signals were reported. Grade ≥3 treatment-related adverse events (TRAEs) were observed in 56% of patients in arm A, 49% of those in arm B, and 49% in arm C.
An exploratory analysis in ORIENT-31 is assessing quality-of-life in arm A vs arm C. Based on second interim analysis finding with a July 4, 2022, cutoff date, longer median time to deterioration of the Global Health Status Dimension Score of EORTC Quality of Life Questionnaire Core 30 was shown with arm A compared with arm C.
“The ORIENT-31 study is the first phase 3 study that met primary endpoints in the world evaluating efficacy of PD-1 inhibitor and chemotherapy with or without bevacizumab in patients with EGFR-mutated non-squamous NSCLC that progressed on prior EGFR-TKI therapy. The results of first and second interim analysis were published in the Lancet Oncology and the Lancet Respiratory Medicine, respectively. That represents the international academia’s recognition of high quality, innovative clinical trial conducted by investigators in China, and is also a milestone marking Innovent’s solid and outstanding capabilities in new drug development. Meanwhile, we look forward to the approval of sintilimab in combination with bevacizumab and chemotherapy based on the results of the ORIENT-31 study can bring new hope to patients with EGFR-mutated non-squamous NSCLC that progressed on prior EGFR-TKI therapy,” said Innovent Hui Zhou, MD, PhD, senior vice president, Innovent Biologics, Inc, in the press release.
1. Innovent updates the results from the ORIENT-31 study of sintilimab plus chemotherapy with or without bevacizumab in patients with EGFR-TKI failed eGFR-mutated non-squamous non-small cell lung cancer in the Lancet Respiratory Medicine. News release. May 8, 2023. Accessed May 8, 2023. https://bit.ly/41dHTJx
2. Sintilimab ± IBI305 plus chemotherapy (pemetrexed + cisplatin) for EGFRm + locally advanced or metastasis non-squamous NSCLC patients after EGFR-TKI treatment failure. ClinicalTrials.gov. Updated September 26, 2022. Accessed May 8, 2023. https://clinicaltrials.gov/ct2/show/NCT03802240?term=NCT03802240&draw=2&rank=1