Findings from the phase 3 ORIENT-31 study shows improved progression-free survival with sintilimab with or without bevacizumab biosimilar injection and chemotherapy in EGFR-mutated non-squamous non-small cell lung-cancer.
Sintilimab with or without anti-VEGF antibody therapy of the bevacizumab biosimilar injection (Byvasda) combined with chemotherapy demonstrated improved progression-free survival (PFS) in patients with EGFR-mutated non-squamous non-small cell lung-cancer (NSCLC) who progressed after EGFR-tyrosine kinase inhibitors (TKI) therapy.1
Findings come from the second interim analysis of the phase 3 ORIENT-31 study (NCT03802240.) The PFS was 7.2 months (95% CI, 6.6-9.3) for patients given sintilimab plus bevacizumab biosimilar injection (arm A) , 5.5 months (95% CI, 4.5-6.1) for sintilimab and chemotherapy group (arm B), and 4.3 months (95% CI, 4.1-5.3) for chemotherapy alone (arm C).
In this analysis, the PFS benefit of arm A vs arm C was consistent with the first interim analysis and arm B showed a statistically significant and clinically meaningful improvement in PFS vs arm C, with a HR of 0.723 (95% CI, 0.552-0.948; P =0.0181. Regarding key secondary end points, overall response rate (ORR) and duration of response (DOR) were also improved in arm B compared with arm C.
"EGFR-TKI targeted therapy is the first treatment choice in NSCLC patients with EGFR sensitive mutation. However, almost all patients will eventually develop TKI-resistance and progression of disease as there are no good treatment options for EGFR-TKI failed NSCLC population. This has become the main concern of clinical physicians,” stated Shun Lu, principal investigator of the ORIENT-31 study, professor from the Oncology Department of Shanghai Chest Hospital, in the press release. “In recent years, immunotherapy has developed rapidly in driver gene-negative cancers, but it has not yet conquered driver genes mutated cancers. In the ORIENT-31 study, sintilimab plus chemotherapy showed a statistically significant improvement in PFS compared to standard platinum-based chemotherapy in EGFR-TKI failed NSCLC. Immunotherapy combination therapy may be a new treatment option for patients living with NSCLC with EGFR-TKI resistance."
The randomized, double-blind, multicenter, phase 3 ORIENT-31 study is evaluating sintilimab, with or without a bevacizumab biosimilar injection, combined with chemotherapy, consisting of pemetrexed and cisplatin in patients with EGFR-mutated locally advanced or metastatic non-squamous NSCLC. Patients must have progressed following EGFR TKI treatment.2
Enrollment was open to patients aged 18 to 75 years of age with histologically or cytologically confirmed stage IIIB/IIIC NSCLC that is unresectable and not fit for radical concurrent chemoradiotherapy, or metastatic/recurrent non-squamous NSCLC. Patients must have an EGFR mutation confirmed by tumor histology or cytology or hematology prior to EGFR-TKI treatment, EGFR-TKI resistance, at least 1 measurable lesion according to RECIST 1.1, and an ECOG performance status of 0 or 1.
In the trial, 476 patients were randomized to receive either sintilimab plus the bevacizumab biosimilar injection combined with chemotherapy, sintilimab plus placebo 2 combined with chemotherapy, or placebo 1 plus placebo 2 combined with chemotherapy. After 4 cycles of combination treatment, patients received maintenance treatment of sintilimab combined with the bevacizumab biosimilar injection and chemotherapy, sintilimab plus placebo 2 and pemetrexed, or placebo 1 plus placebo 2 and pemetrexed. This continued until radiographic disease progression, unacceptable toxicity or any other conditions that require treatment discontinuation.
The primary end point is PFS as assessed by Independent Imaging Assessment Committee with secondary end points including overall survival (OS), ORR, PFS as assessed by investigators, disease control rate, time to response, and DOR.
The safety profile of this study was consistent with previously reported studies examining sintilimab and bevacizumab biosimilar injection, and there were no new or unexpected safety signals observed.
Overall, this study is the first prospective, double-blind, phase 3 study to reveal a significant PFS benefit of an anti-PD-1 antibody with or without VEGF inhibitors and chemotherapy vs the standard care of therapy in this patient population.