Toripalimab plus chemo improves survival in NSCLC

The addition of toripalimab to first-line chemotherapy led to significantly improved progression-free survival (PFS) and overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC) without EGFR/ALK mutations, according to the updated results of the CHOICE-01* trial presented at the ASCO Plenary 2022.

This phase III, multicentre, double-blind, placebo-controlled trial involved 465 treatment-naïve patients with advanced NSCLC but without EGFR/ALK mutations. Participants were randomized in a 2:1 ratio to receive either intravenous toripalimab 240 mg (n=309; mean age 63 years) or placebo (n=156; mean age 61 years) every 3 weeks in addition to 4–6 cycles of chemotherapy**, followed by maintenance treatment with toripalimab or placebo plus standard of care until disease progression, intolerable toxicity, or after completion of 2 years of treatment. [ASCO Plenary 2022, abstract 362936]

As of data cut-off on October 31, 2021, patients who received toripalimab + chemotherapy had a significantly improved PFS than those who received placebo + chemotherapy (median, 8.4 vs 5.6 months; stratified hazard ratio [HR] for disease progression or death, 0.48; two-sided p<0.0001).

The 1-year PFS rate was higher among those treated with toripalimab + chemotherapy compared with placebo + chemotherapy (36.7 percent vs 17.2 percent).

The median OS was not yet reached in the toripalimab + chemotherapy arm compared with 17.1 months in the placebo + chemotherapy arm at this interim analysis (stratified HR for death, 0.69; two-sided p=0.0099). “The improvement in OS was observed, despite a very high crossover rate,” said lead author Dr Jie Wang from the National Cancer Center/Cancer Hospital in Beijing, China.

The PFS and OS benefits were also observed in the toripalimab + chemotherapy arm, regardless of PD-L1 expression status.

Using whole-exome sequencing, patients with high tumour mutational burden (TMB-H ≥10 mutations/million base pairs) treated with toripalimab + chemotherapy achieved a significantly better PFS than those treated with placebo + chemotherapy (13.1 vs 5.5 months; interaction p=0.026).

Among patients with mutations in the FA-PI3K-Akt pathway, a significantly better PFS and OS was observed in the toripalimab + chemotherapy arm than those in the placebo + chemotherapy arm (median 8.9 vs 4.17 months; interaction p=0.0003 for PFS and not reached vs 13.77 months; interaction p=0.006 for OS).

Grade ≥3 treatment-emergent adverse events (TEAEs) occurred at a similar rate between the toripalimab + chemotherapy and placebo + chemotherapy arms (78.6 percent vs 82.1 percent). However, more patients in the toripalimab arm discontinued study treatment due to AEs than those in the placebo arm (14.3 percent vs 3.2 percent), with no new safety signals observed.

“Toripalimab in combination with chemotherapy provided a significant improvement in PFS and OS compared with chemotherapy alone[, with a manageable safety profile,] in advanced NSCLC without EGFR/ALK mutations,” said Wang.

“These results support the use of toripalimab with chemotherapy as first-line therapy for patients with advanced NSCLC without EGFR/ALK mutations,” she added.

*CHOICE-01: A study to evaluate the efficacy and safety of toripalimab or placebo combined with chemotherapy in treatment-naive advanced NSCLC

**Chemotherapy: Pemetrexed + cisplatin/carboplatin for 4–6 cycles, followed by pemetrexed for non-squamous carcinoma and nab-paclitaxel + carboplatin for squamous carcinoma for 4–6 cycles