Durvalumab Versus Chemotherapy as First-line Treatment for Metastatic NSCLC With Tumor PD-L1 Expression ≥25%: Results from the Randomized Phase 3 PEARL Study

Shun Lu; Lin Wu; Qiming Wang; Ziping Wang; Dongqing Lv; Rui Ma; Bo Zhu; Ngoc van Tran; Liyan Jiang; Kejun Nan; Konstantin Laktionov; Stephen Clarke; Minghao Song; Helen Mann; Yinglei Liu; Xiaojin Shi; Yi-Long Wu; PEARL investigators

doi:10.1016/j.jtho.2024.10.024

Durvalumab Versus Chemotherapy as First-line Treatment for Metastatic NSCLC With Tumor PD-L1 Expression ≥25%: Results from the Randomized Phase 3 PEARL Study

J Thorac Oncol. 2024 Nov 7:S1556-0864(24)02433-X. doi: 10.1016/j.jtho.2024.10.024. Online ahead of print.

Authors

Shun Lu¹, Lin Wu², Qiming Wang³, Ziping Wang⁴, Dongqing Lv⁵, Rui Ma⁶, Bo Zhu⁷, Ngoc van Tran⁸, Liyan Jiang⁹, Kejun Nan¹⁰, Konstantin Laktionov¹¹, Stephen Clarke¹², Minghao Song¹³, Helen Mann¹⁴, Yinglei Liu¹⁵, Xiaojin Shi¹³, Yi-Long Wu¹⁶; PEARL investigators

Affiliations

¹ Shanghai Lung Cancer Centre, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
² The Department of Thoracic Medical Oncology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
³ Department of Internal Medicine, Henan Cancer Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
⁴ The First Department of Thoracic Oncology, Beijing Cancer Hospital, Beijing, China.
⁵ Department of Respiratory Medicine, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Taizhou, China.
⁶ Department of Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China.
⁷ Institute of Cancer, Xinqiao Hospital of the Third Military Medical University, Chongqing, China.
⁸ Respiratory Department, Cho Ray Hospital, Ho Chi Minh City, Vietnam.
⁹ Pulmonary Medicine Department, Shanghai Chest Hospital, Jiao Tong University, Shanghai, China.
¹⁰ Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
¹¹ Federal State Budgetary Institution "N.N.Blokhin National Medical Research Center of Oncology"of the Ministry of Health of the Russian Federation (N.N. Blokhin NMRCO), Moscow, Russia.
¹² Northern Sydney Cancer Centre, Royal North Shore Hospital, St Leonards, NSW, Australia.
¹³ AstraZeneca, Gaithersburg, MD, USA.
¹⁴ AstraZeneca, Cambridge, UK.
¹⁵ AstraZeneca, Shanghai, China.
¹⁶ Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangzhou, China. Electronic address: syylwu@live.cn.

PMID: 39521433
DOI: 10.1016/j.jtho.2024.10.024

Abstract

Introduction: PEARL (NCT03003962) is an open-label, phase 3 study comparing first-line durvalumab monotherapy with chemotherapy in patients with metastatic non-small cell lung cancer (mNSCLC [EGFR/ALK wild type]) with PD-L1 tumor cell (TC) membrane expression status ≥25%. We report the final analysis of PEARL.

Methods: Adults (N=669) with previously untreated Stage IV mNSCLC were randomized (1:1) to durvalumab 20mg/kg every 4 weeks or chemotherapy every 3 weeks for 4 to 6 cycles. Dual primary endpoints were overall survival (OS) in the PD-L1 TC ≥25% and the PD-L1 TC ≥25% low risk of early mortality (LREM) populations.

Results: Durvalumab was associated with a numerical reduction in the risk of death versus chemotherapy in the PD-L1 TC ≥25% population (OS hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.71, 0.99, p = 0.037; median OS 14.6 months [95% CI: 12.2, 16.9] versus 12.8 months [95% CI: 10.1, 14.7], respectively). In the PD-L1 TC ≥25% LREM population the OS HR for durvalumab versus chemotherapy was 0.96 (95% CI: 0.79, 1.15, p = 0.628); median OS 14.6 months (95% CI: 12.6, 17.2) versus 15.0 months (95% CI: 13.1, 16.8), respectively. In the safety population, the incidence of grade 3/4 treatment-related adverse events was 15.5% (durvalumab) and 45.9% (chemotherapy).

Conclusions: Durvalumab did not statistically significantly improve OS versus chemotherapy as first-line treatment in patients with mNSCLC and PD-L1 TC ≥25%. The numerical improvement in OS was consistent with previous studies of first-line immune checkpoint inhibitor monotherapy in patients with mNSCLC.

Keywords: Durvalumab; PD-L1; PEARL; chemotherapy; metastatic NSCLC.