Toripalimab/Chemo Combo Provides Significant Survival Benefit in NSCLC Without EGFR/ALK Mutations

The addition of toripalimab to chemotherapy resulted in improved progression-free survival (PFS) and overall survival (OS) vs chemotherapy alone in patients with treatment-naïve advanced non–small cell lung cancer (NSCLC) without EGFR or ALK mutations, according to data from the phase 3 CHOICE-01 trial (NCT03856411) presented during the March 2022 ASCO Plenary Series.¹

Findings from the final PFS analysis demonstrated that patients who were administered toripalimab plus chemotherapy experienced a median PFS of 8.4 months (95% CI, 7.7-9.6) vs 5.6 months (95% CI, 5.5-6.8) in those who received placebo plus chemotherapy (HR, 0.49; 95% CI, 0.39-0.61; two-sided P < .0001). Additionally, the 1-year PFS rate was 36.7% (95% CI, 30.9%-42.5%) in the toripalimab arm vs 17.2% (95% CI, 11.4%-24.0%) in the control arm.

“The PFS effect favored toripalimab in all major subgroups, including histology, PD-L1 expression, and tumor mutational burden,” lead study author Jie Wang, MD, PhD, of the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, said in a presentation on the data.

CHOICE-01 enrolled patients with advanced squamous and nonsquamous NSCLC who had treatment-naïve, locally advanced or metastatic disease. Patients needed to have measurable disease per RECIST v1.1 criteria, an ECOG performance status of 0 or 1, and tumor tissue available for PD-L1 expression testing. Patients could not have known sensitizing EGFR mutations or ALK fusions.

A total of 450 study participants were randomized 2:1 to receive 240 mg of intravenous (IV) toripalimab (n = 309) or IV placebo (n = 156) on day 1 of every 3-week cycle for up to 2 years. In both arms, patients with nonsquamous disease also received pemetrexed at 500 mg/m2 on day 1 plus cisplatin at 75 mg/m2 on day 1/carboplatin at area under the curve 5 on day 1 for 4 to 6 cycles, followed by pemetrexed; those with squamous disease were given nab-paclitaxel (Abraxane) at 100 mg/m2 on days 1, 8, and 15, plus carboplatin for 4 to 6 cycles.

Notably, those who experienced disease progression on placebo were permitted to cross over to receive toripalimab.

The primary end point of the study was PFS per RECIST v1.1 criteria and investigator review. Secondary end points included OS, PFS by blinded independent review committee assessment, overall response rate (ORR), duration of response (DOR), disease control rate, time to response, and safety.

The median ages of patients on the investigative and control arms were 63 years (range, 36-75) and 61 years (range, 29-75), respectively. The majority of patients were male (79.9% vs 83.3%, respectively), had an ECOG performance status of 1 (78.6% vs 76.9%), presented with nonsquamous disease (52.4% vs 53.2%), had a PD-L1 expression of 1% or higher on tumor cells (65.0% vs 66.0%), were frequent smokers (68.9% vs 68.6%), and presented with stage IVA disease (45.6% vs 52.6%).

In the toripalimab/chemotherapy arm, 1.6% of patients had brain metastases, 8.4% had liver metastases, and 17.2% had 3 or more metastatic sites. In the placebo/chemotherapy arm, 9.0% of patients had liver metastases, and 15.4% had 3 or more metastatic sites. Moreover, 4.2% of patients on the investigative arm previously received neoadjuvant/adjuvant therapy vs 5.8% of those in the control arm.

Data from the interim OS analysis showed that the median OS in the toripalimab arm was not estimable (NE; 95% CI, 21.7–NE) vs 17.1 months (95% CI, 14.4-22.2) in the control arm (HR, 0.69; 95% CI, 0.52-0.92; two-sided P = .0099. The 1-year OS rates in the investigative and control arms were 74.0% (95% CI, 68.7%-78.6%) and 72.8% (95% CI, 65.0%-79.1%), respectively; the 2-year OS rates were 51.2% (95% CI, 43.6%-58.3%) and 33.9% (95% CI, 22.9%-45.2%), respectively.

Notably, there was extension crossover in the placebo arm. Ninety-two percent of 88 patients received toripalimab upon disease progression, and 65.4% of patients on the control arm went on to receive subsequent anti–PD-1/PD-L1 treatment.

OS benefit favored the investigative regimen in most subsets analyzed, with the exception of those with squamous cell carcinoma (unstratified HR, 0.99; 95% CI, 0.67-1.48), those with liver metastases (unstratified HR, 1.05; 95% CI, 0.50-2.35), and those who received prior neoadjuvant/adjuvant therapy against their disease (unstratified HR, 1.27; 95% CI, 0.21-9.86).

The addition of toripalimab to chemotherapy resulted in an ORR of 65.7% (95% CI, 60.1%-71.0%) vs 46.2% (95% CI, 38.2%-54.3%) with chemotherapy alone, translating to a 19.5% difference between the arms (95% CI, 10.1%-28.8%; P < .0001). Notably, all responses achieved in both cohorts were partial responses (PRs). The PR rate in the investigative arm was 65.7% vs 46.2% in the control arm. Additionally, the median DOR in the toripalimab arm was 8.4 months (95% CI, 6.9-12.9) vs 4.2 months (95% CI, 4.0-5.6) in the control arm (HR, 0.38; 95% CI, 0.28-0.53; P < .0001).

Among patients with PD-L1–positive disease (n = 304), those who received toripalimab experienced a median PFS of 8.9 months vs 6.4 months with chemotherapy alone (HR, 0.52; 95% CI, 0.39-0.69). The 12-month PFS rates in the investigative and control arms were 42.0% and 20.7%, respectively. The median OS in this subset was NE with toripalimab/chemotherapy vs 20.3 months with chemotherapy alone (HR, 0.70; 95% CI, 0.49-1.01). The 12-month OS rates in the investigative and control arms were 74.8% and 76.3%, respectively; the 24-month rates were 53.6% and 35.6%, respectively.

Patients with PD-L1–negative disease (n = 161) had a median PFS of 8.3 months with toripalimab/chemotherapy vs 5.5 months with chemotherapy alone (HR, 0.49; 95% CI, 0.34-0.71). The 12-month PFS rates in the investigative and control arms were 26.9% and 10.6%, respectively. The median OS was 21.2 months with toripalimab/chemotherapy vs 14.1 months with chemotherapy alone (HR, 0.68; 95% CI, 0.44-1.07). The 12-month OS rates in the investigative and control arms were 72.5% and 66.0%, respectively; at 24 months, these rates were 46.8% and 34.6%, respectively.

In the subset of patients with high tumor mutational burden (TMB; n = 122), the median PFS was 13.1 months with the investigative regimen vs 5.5 months with the control regimen (HR, 0.34; 95% CI, 0.21-0.54). The 12-month PFS rate in this subset with toripalimab plus chemotherapy was 52.5% vs 15.3% with chemotherapy alone. The median OS was NE in the investigative arm vs 20.3 months in the control arm (HR, 0.67; 95% CI, 0.38-1.19). The 12-month OS rate in the toripalimab combination arm was 77.7% vs 84.1% in the chemotherapy-alone arm; at 24, months, these rates were 52.2% and 41.1%, respectively.

Among those with low TMB (n = 272), the median PFS with toripalimab/chemotherapy was 8.3 months vs 6.5 months with chemotherapy alone (HR, 0.62; 95% CI, 0.46-0.83). The 12-month PFS rates in the investigative and control arms were 32.8% and 18.5%, respectively. In this subset, the median OS was NE with toripalimab/chemotherapy vs 16.2 months with chemotherapy alone (HR, 0.68; 95% CI, 0.47-0.98). The 12-month OS rates in the investigative and control arms were 73.4% and 69.4%, respectively; the 24-month rates were 51.3% and 35.0%, respectively.

Regarding safety, any-grade treatment-emergent adverse effects (TEAEs) occurred in 99.0% of those in the toripalimab arm and 100% of those in the control arm; grade 3 or higher TEAEs were experienced by 78.6% and 82.1% of patients, respectively. Serious AEs occurred in 44.8% of those in the investigative arm vs 35.3% of those in the control arm.

The most common grade 3 or higher TEAEs experienced with the combination included anemia, neutropenia, leukopenia, thrombocytopenia, alanine aminotransferase increased, fatigue, and decreased appetite.

Investigator-determined immune-related AEs were reported in 49.4% and 21.2% of patients in the toripalimab and control arms, respectively; these effects were grade 3 or higher in 15.6% and 3.2% of patients, respectively. Infusion-related reactions occurred in 2.6% of those in the investigative arm and 1.3% of those in the control arm.

Additionally, 14.3% of patients in the toripalimab arm vs 3.2% of those in the control arm discontinued treatment due to TEAEs; 63.0% and 55.1% of patients, respectively, required treatment interruptions. TEAEs led to death in 5.5% and 2.6% of patients in the toripalimab and control arms, respectively.

Reference

1. Wang J. Final progression-free survival, interim overall survival and biomarker analyses of CHOICE-01: a phase 3 study of toripalimab versus placebo in combination with first-line chemotherapy for advanced NSCLC without EGFR/ALK mutations. J Clin Oncol. 2022;40(suppl 36):362936. doi:10.1200/JCO.2022.40.36_suppl.362936