Originally published by 2 Minute Medicine^® (view original article). Reused on AccessMedicine with permission.

1. In the toripalimab arm, progression-free survival was longer, overall survival at the second interim analysis was longer, and objective response rate and duration of response were significantly better.

2. Incidence of adverse events was similar between both arms. The most common adverse events of grades 3 or more were neutropenia, leukopenia and anemia in both arms.

Evidence Rating Level: 1 (Excellent)

Study Rundown:

Immune checkpoint inhibitors (ICIs) have demonstrated superior efficacy compared to chemotherapy in advanced stage non-small-cell lung cancer (NSCLC) patients. This study explored the efficacy and safety of toripalimab (an ICI) in combination with traditional chemotherapy in treatment-naïve NSCLC patients that lack a driver mutation. Patients were randomly assigned to receive chemotherapy and either toripalimab or placebo. Random assignment was stratified based on PD-L1 expression levels, among other factors. In the toripalimab arm, progression-free survival (PFS) was longer, overall survival (OS) at the second interim analysis was longer, and objective response rate (ORR) and duration of response (DOR) were significantly better. No significant differences were found between PD-L1 statuses. Genomic analysis showed that patients in the toripalimab arm with mutations in the focal adhesion-PI3K-Akt signalling pathway had better PFS and OS. Patients in the toripalimab arm with high tumour mutational burden (TMB) also had better PFS. The incidence of adverse events was similar between both arms. The most common adverse events of grades 3 or more were neutropenia, leukopenia and anemia in both arms. Limitations to this study include its generalizability as all patients were of Chinese origin and the male predominance. The strengths of this study are that it has limited bias given the design and that it provides new perspectives on patient selection based on tumour genetic alternations. Overall, toripalimab addition to chemotherapy is a viable treatment option.

Click to read the study in the JCO

Relevant Reading: Immune checkpoint inhibitors in non-small cell lung cancer: progress, challenges, and prospects

In-Depth [randomized control trial]:

This phase III trial randomly assigned 465 treatment-naïve NSCLC patients without EGFR/ALK mutations to receive chemotherapy and either toripalimab or placebo; 309 were in the toripalimab arm and 156 were in the placebo arm. Random assignment was stratified based on PD-L1 expression levels. Median PFS was 8.4 months for toripalimab arm and 5.6 months for the placebo arm (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.39 to 61; P=0.0001). OS at the second interim analysis was not reached and 17.1 months, respectively (HR, 0.69; 95% CI, 0.53 to 0.92; P=0.0099). ORR was 65.7% and 46.2%, respectively (P<0.0001) and DoR was 8.4 months and 4.2 months, respectively (HR, 0.38; 95% CI, 0.28 to 0.53). In the high TMB subgroups, PFS was 13.1 months and 5.5 months, respectively (HR, 0.34; 95% CI, 0.21 to 0.54; P=0.026). Patients with mutations in the focal adhesion-PI3K-Akt signalling pathway had better PFS and OS in the toripalimab arm (P<0.001). The incidence of grades 3 or more adverse events was 78.6% for the toripalimab arm and 82.1% for the placebo arm. Most common adverse events of grades 3 or more were neutropenia (55.5% vs. 53.8%, respectively), leukopenia (35.7% vs. 41.7%) and anemia (29.9% and 35.9%). Overall, toripalimab addition to chemotherapy showed clinical benefit in treatment-naïve advanced stage NSCLC patients that lack a driver mutation.

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