Perioperative toripalimab plus platinum-based chemotherapy

A phase III randomized trial (Neotorch [NCT04158440]) evaluated the efficacy and safety of toripalimab in combination with neoadjuvant platinum-based chemotherapy followed by maintenance toripalimab versus chemotherapy alone in patients with resectable stage II, IIIA, or IIIB (N2) NSCLC without EGFR or ALK alterations. Patients were stratified by disease stage (II, IIIA, or IIIB), PD-L1 tumor expression status (≥1%, <1%, or not evaluable using the JS311IHC staining assay), planned surgical approach (pneumonectomy or lobectomy), and histological subtype (squamous vs. nonsquamous). A total of 501 patients with stage II to III resectable NSCLC were randomly assigned to receive either (1) toripalimab plus platinum-based chemotherapy for three cycles before surgery and one cycle after surgery followed by single-agent maintenance toripalimab for up to 13 cycles or (2) platinum-based chemotherapy alone for three cycles before surgery and one cycle after surgery. Coprimary end points were EFS (defined as time from randomization to the first documentation of disease progression leading to the inability to operate, postoperative progression, or local or distant recurrence/death from any cause) and major pathological response (≤10% or less viable tumor cells in the tumor bed). Secondary end points included OS, pathological complete response, DFS after surgery, and safety.[24]

A phase III randomized trial (Neotorch [NCT04158440]) evaluated the efficacy and safety of toripalimab in combination with neoadjuvant platinum-based chemotherapy followed by maintenance toripalimab versus chemotherapy alone in patients with resectable stage II, IIIA, or IIIB (N2) NSCLC without EGFR or ALK alterations. Patients were stratified by disease stage (II, IIIA, or IIIB), PD-L1 tumor expression status (≥1%, <1%, or not evaluable using the JS311IHC staining assay), planned surgical approach (pneumonectomy or lobectomy), and histological subtype (squamous vs. nonsquamous). A total of 501 patients with stage II to III resectable NSCLC were randomly assigned to receive either (1) toripalimab plus platinum-based chemotherapy for three cycles before surgery and one cycle after surgery followed by single-agent maintenance toripalimab for up to 13 cycles or (2) platinum-based chemotherapy alone for three cycles before surgery and one cycle after surgery. Coprimary end points were EFS (defined as time from randomization to the first documentation of disease progression leading to the inability to operate, postoperative progression, or local or distant recurrence/death from any cause) and major pathological response (≤10% or less viable tumor cells in the tumor bed). Secondary end points included OS, pathological complete response, DFS after surgery, and safety.[24]

In a prespecified interim analysis of EFS in patients with stage III NSCLC (n = 404) after a median follow-up of 18.3 months (IQR, 12.7–22.5 months), the median EFS was not reached (95% CI, 24.4 months–NR) in the toripalimab group and was 15.1 months (95% CI, 10.6–21.9) in the placebo group (HR, 0.40; 95% CI, 0.28–0.57; P < .001).

A phase III randomized trial (Neotorch [NCT04158440]) evaluated the efficacy and safety of toripalimab in combination with neoadjuvant platinum-based chemotherapy followed by maintenance toripalimab versus chemotherapy alone in patients with resectable stage II, IIIA, or IIIB (N2) NSCLC without EGFR or ALK alterations. Patients were stratified by disease stage (II, IIIA, or IIIB), PD-L1 tumor expression status (≥1%, <1%, or not evaluable using the JS311IHC staining assay), planned surgical approach (pneumonectomy or lobectomy), and histological subtype (squamous vs. nonsquamous). A total of 501 patients with stage II to III resectable NSCLC were randomly assigned to receive either (1) toripalimab plus platinum-based chemotherapy for three cycles before surgery and one cycle after surgery followed by single-agent maintenance toripalimab for up to 13 cycles or (2) platinum-based chemotherapy alone for three cycles before surgery and one cycle after surgery. Coprimary end points were EFS (defined as time from randomization to the first documentation of disease progression leading to the inability to operate, postoperative progression, or local or distant recurrence/death from any cause) and major pathological response (≤10% or less viable tumor cells in the tumor bed). Secondary end points included OS, pathological complete response, DFS after surgery, and safety.[24]

The 1- and 2-year EFS rates were 84.4% and 64.7%, respectively, in the toripalimab group and 57.0% and 38.7%, respectively, in the placebo group. A consistent effect on EFS, favoring toripalimab, was observed in all subgroups.

A phase III randomized trial (Neotorch [NCT04158440]) evaluated the efficacy and safety of toripalimab in combination with neoadjuvant platinum-based chemotherapy followed by maintenance toripalimab versus chemotherapy alone in patients with resectable stage II, IIIA, or IIIB (N2) NSCLC without EGFR or ALK alterations. Patients were stratified by disease stage (II, IIIA, or IIIB), PD-L1 tumor expression status (≥1%, <1%, or not evaluable using the JS311IHC staining assay), planned surgical approach (pneumonectomy or lobectomy), and histological subtype (squamous vs. nonsquamous). A total of 501 patients with stage II to III resectable NSCLC were randomly assigned to receive either (1) toripalimab plus platinum-based chemotherapy for three cycles before surgery and one cycle after surgery followed by single-agent maintenance toripalimab for up to 13 cycles or (2) platinum-based chemotherapy alone for three cycles before surgery and one cycle after surgery. Coprimary end points were EFS (defined as time from randomization to the first documentation of disease progression leading to the inability to operate, postoperative progression, or local or distant recurrence/death from any cause) and major pathological response (≤10% or less viable tumor cells in the tumor bed). Secondary end points included OS, pathological complete response, DFS after surgery, and safety.[24]

After surgical resection, a major pathological response occurred in 98 patients (48.5%) in the toripalimab group and 17 patients (8.4%) in the placebo group (between group difference, 40.2%; 95% CI, 32.2%–48.1%; P < .001).