IASLC World Conference on Lung Cancer
IASLC World Conference on Lung Cancer
Perspective from Howard (Jack) West, MD
Perspective from Misako Nagasaka, MD
Source/Disclosures
Source:

Zhang L, et al. Abstract LBA 1. Presented at: International Association for the Study of Lung Cancer World Conference on Lung Cancer Virtual Presidential Symposium; Aug. 8, 2020.

Disclosures: Eli Lilly & Co. and Innovent Biologics funded this study. Zhang reports research funding from Eli Lilly & Co. and Pfizer. Please see the abstract for all other researchers’ relevant financial disclosures.
August 12, 2020
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Sintilimab plus pemetrexed, chemotherapy extends PFS in non-small cell lung cancer subset

Perspective from Howard (Jack) West, MD
Perspective from Misako Nagasaka, MD
Source/Disclosures
Source:

Zhang L, et al. Abstract LBA 1. Presented at: International Association for the Study of Lung Cancer World Conference on Lung Cancer Virtual Presidential Symposium; Aug. 8, 2020.

Disclosures: Eli Lilly & Co. and Innovent Biologics funded this study. Zhang reports research funding from Eli Lilly & Co. and Pfizer. Please see the abstract for all other researchers’ relevant financial disclosures.
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The addition of sintilimab to pemetrexed and platinum chemotherapy conferred a significant PFS benefit for a subset of patients with nonsquamous non-small cell lung cancer, according to results of an interim analysis of the ORIENT-11 study.

Researchers observed the benefit specifically among patients with locally advanced or metastatic disease and no EGFR or ALK mutations.

Sintilimab demonstrated a PFS benefit among patients in all subgroups based on PD-L1 tumor proportion score.
Sintilimab showed a PFS benefit in all subgroups based on PD-L1 tumor proportion score.

Li Zhang, MD, researcher at Sun Yat-sen University Cancer Center in China, presented the results during the International Association for the Study of Lung Cancer World Conference on Lung Cancer Virtual Presidential Symposium. The findings were published simultaneously in Journal of Thoracic Oncology.

“Sintilimab [Tyvyt; Eli Lilly & Co., Innovent Biologics] is a fully human IgG4 monoclonal antibody that blocks the binding of PD-1 to PD-L1 or PD-L2, with high affinity to human PD-1 and high PD-1 receptor occupancy,” Zhang said during the presentation. “Previously, sintilimab in combination with pemetrexed and a platinum-based chemotherapy had shown promising activity for nonsquamous non-small cell lung cancer in a phase 1b study. Based upon these data, we sought to evaluate the efficacy and safety of sintilimab in combination with pemetrexed and platinum-based chemotherapy in a randomized phase 3 study.”

The ORIENT-11 study included 397 patients with previously untreated locally advanced or metastatic nonsquamous NSCLC without EGFR or ALK mutations and an ECOG performance status of 0 or 1.

Researchers randomly assigned patients 2:1 to 200 mg sintilimab (n = 266; median age, 61 years; 76.7% men) or placebo (n = 131; median age, 61 years; 75.6% men) plus 500 mg/m2 pemetrexed and either 75 mg/m2 cisplatin or carboplatin area under the curve 5 every 3 weeks for four cycles. Patients then received maintenance therapy with either sintilimab or placebo with pemetrexed. Treatment continued until disease progression, and participants in the placebo group could cross over to sintilimab.

PFS served as the primary endpoint. Secondary endpoints included OS, overall response rate, time to response, duration of response and safety. Researchers had planned to conduct an interim analysis when 70% of PFS events occurred. Data cutoff was Nov. 15, 2019.

At a median follow-up of 8.9 months (range, 0.6-14.8), 198 PFS events or deaths had occurred. Overall, 85.3% (n = 227) of patients assigned the sintilimab combination and 80.2% (n = 105) assigned the placebo combination completed all four cycles of induction treatment and received maintenance therapy.

Median treatment duration was 7.1 months in the sintilimab group vs. 5.5 months in the placebo group. The effective crossover rate in the placebo group was 35.9%. Overall, 31.2% (n = 83) of patients in the sintilimab group and 35.1% (n = 46) in the placebo group continued study treatment beyond first disease progression.

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Results showed median PFS of 8.9 months with the sintilimab combination vs. 5 months with the placebo combination (HR = 0.48; 95% CI, 0.36-0.64). Researchers reported 6-month PFS rates of 68.3% (95% CI, 62-73.8) for the sintilimab group vs. 42% (95% CI, 32.8-50.9) for the placebo group.

The HR for patients with brain metastases in the sintilimab vs. placebo group was 0.57 (95% CI, 0.28-1.18) compared with an HR of 0.46 (95% CI, 0.34-0.64) for those without brain metastases.

Sintilimab also demonstrated a PFS benefit among patients who never smoked (HR = 0.55; 95% CI, 0.33-0.92), as well as among those in all subgroups based on PD-L1 tumor proportion score (see Table).

Median OS was not reached in either treatment group, but researchers observed a trend toward improvement in the sintilimab group (HR = 0.6; 95% CI, 0.4-0.92).

The confirmed ORR was 51.9% (95% CI, 45.7-58) with the sintilimab combination vs. 29.8% (95% CI, 22.1-38.4) with the placebo combination (P = .00003), and the time to treatment response was shorter with the sintilimab combination (1.5 months vs. 2.6 months). Median duration of response was not reached with sintilimab vs. 5.5 months with placebo.

Grade 3 or higher adverse events occurred more often with the sintilimab combination (61.7% vs. 58.8%). The most common of these included decreased neutrophil count (36.5% vs. 30.5%), anemia (15% vs. 19.1%) and decreased white blood cell count (14.7% vs. 15.3%).

“Sintilimab plus chemotherapy significantly improved PFS and led to a nominally significant improvement in OS, with a manageable safety profile and no new safety signals,” Zhang said.

Future research will focus on biomarker exploration in this setting, Zhang added.

References