Adjuvant immunotherapy

The phase III, multicenter, open-label PEARLS/KEYNOTE-091 trial (NCT02504372) randomly assigned 1,177 patients with completely resected stage IB (tumor >4 cm) to stage IIIA NSCLC to receive pembrolizumab (200 mg every 3 weeks) or placebo for up to 18 cycles, or until disease progression, or unacceptable toxicity. Patients started study treatment after resection or, if indicated, after adjuvant chemotherapy (maximum of four cycles). The dual primary end points were DFS in the overall study population and DFS in patients with a PD-L1 tumor proportion score (TPS) of 50% or greater, as determined using the PD-L1 IHC 22C3 pharmDx assay. These end points were reported in a prespecified interim analysis after a median follow-up of 35.6 months (interquartile range, 27.1–45.5).[27][Level of evidence B1]

The phase III, multicenter, open-label PEARLS/KEYNOTE-091 trial (NCT02504372) randomly assigned 1,177 patients with completely resected stage IB (tumor >4 cm) to stage IIIA NSCLC to receive pembrolizumab (200 mg every 3 weeks) or placebo for up to 18 cycles, or until disease progression, or unacceptable toxicity. Patients started study treatment after resection or, if indicated, after adjuvant chemotherapy (maximum of four cycles). The dual primary end points were DFS in the overall study population and DFS in patients with a PD-L1 tumor proportion score (TPS) of 50% or greater, as determined using the PD-L1 IHC 22C3 pharmDx assay. These end points were reported in a prespecified interim analysis after a median follow-up of 35.6 months (interquartile range, 27.1–45.5).[27][Level of evidence B1]

In the overall study population, the median DFS was 53.6 months (95% CI, 39.2 to NR) in the pembrolizumab group and 42.0 months (95% CI, 31.3–NR) in the placebo group (HR, 0.76; 95% CI, 0.63–0.91, P = .0014).

The phase III, multicenter, open-label PEARLS/KEYNOTE-091 trial (NCT02504372) randomly assigned 1,177 patients with completely resected stage IB (tumor >4 cm) to stage IIIA NSCLC to receive pembrolizumab (200 mg every 3 weeks) or placebo for up to 18 cycles, or until disease progression, or unacceptable toxicity. Patients started study treatment after resection or, if indicated, after adjuvant chemotherapy (maximum of four cycles). The dual primary end points were DFS in the overall study population and DFS in patients with a PD-L1 tumor proportion score (TPS) of 50% or greater, as determined using the PD-L1 IHC 22C3 pharmDx assay. These end points were reported in a prespecified interim analysis after a median follow-up of 35.6 months (interquartile range, 27.1–45.5).[27][Level of evidence B1]

In the PD-L1 TPS ≥50% population, the median DFS was not reached with either pembrolizumab (95% CI, 44.3–NR) or placebo (95% CI, 35.8–NR) (HR, 0.82; 95% CI, 0.57–1.18; P = .14).

The phase III, multicenter, open-label PEARLS/KEYNOTE-091 trial (NCT02504372) randomly assigned 1,177 patients with completely resected stage IB (tumor >4 cm) to stage IIIA NSCLC to receive pembrolizumab (200 mg every 3 weeks) or placebo for up to 18 cycles, or until disease progression, or unacceptable toxicity. Patients started study treatment after resection or, if indicated, after adjuvant chemotherapy (maximum of four cycles). The dual primary end points were DFS in the overall study population and DFS in patients with a PD-L1 tumor proportion score (TPS) of 50% or greater, as determined using the PD-L1 IHC 22C3 pharmDx assay. These end points were reported in a prespecified interim analysis after a median follow-up of 35.6 months (interquartile range, 27.1–45.5).[27][Level of evidence B1]

OS data were immature at the time of prespecified interim analysis.

The phase III, multicenter, open-label PEARLS/KEYNOTE-091 trial (NCT02504372) randomly assigned 1,177 patients with completely resected stage IB (tumor >4 cm) to stage IIIA NSCLC to receive pembrolizumab (200 mg every 3 weeks) or placebo for up to 18 cycles, or until disease progression, or unacceptable toxicity. Patients started study treatment after resection or, if indicated, after adjuvant chemotherapy (maximum of four cycles). The dual primary end points were DFS in the overall study population and DFS in patients with a PD-L1 tumor proportion score (TPS) of 50% or greater, as determined using the PD-L1 IHC 22C3 pharmDx assay. These end points were reported in a prespecified interim analysis after a median follow-up of 35.6 months (interquartile range, 27.1–45.5).[27][Level of evidence B1]

No new safety signals were identified in this study.

IMpower010 (NCT02486718) was a phase III, multicenter, open-label trial that randomly assigned 1,005 patients with surgically resected stage IB (tumor >4 cm) to stage IIIA NSCLC. Patients received atezolizumab (1,200 mg every 21 days intravenously) or best supportive care for 16 cycles or 1 year after standard adjuvant platinum-based chemotherapy. Patients were enrolled after resection if they were eligible for cisplatin-based chemotherapy and were randomized after completion of chemotherapy if they remained eligible and did not experience disease progression. The primary end point was investigator-assessed DFS.[28]

IMpower010 (NCT02486718) was a phase III, multicenter, open-label trial that randomly assigned 1,005 patients with surgically resected stage IB (tumor >4 cm) to stage IIIA NSCLC. Patients received atezolizumab (1,200 mg every 21 days intravenously) or best supportive care for 16 cycles or 1 year after standard adjuvant platinum-based chemotherapy. Patients were enrolled after resection if they were eligible for cisplatin-based chemotherapy and were randomized after completion of chemotherapy if they remained eligible and did not experience disease progression. The primary end point was investigator-assessed DFS.[28]

The primary end point was tested hierarchically, first in the stage II to IIIA population subgroup whose tumors expressed PD-L1 on at least 1% of tumor cells (using the SP263 antibody), then in all patients in the stage II to IIIA population, and finally in the ITT population (stage IB to IIIA). Of the 882 patients who were randomly assigned and had stage II to IIIA disease, 476 had tumors expressing PD-L1 on at least 1% of tumor cells per SP263.[28][Level of evidence B1]

IMpower010 (NCT02486718) was a phase III, multicenter, open-label trial that randomly assigned 1,005 patients with surgically resected stage IB (tumor >4 cm) to stage IIIA NSCLC. Patients received atezolizumab (1,200 mg every 21 days intravenously) or best supportive care for 16 cycles or 1 year after standard adjuvant platinum-based chemotherapy. Patients were enrolled after resection if they were eligible for cisplatin-based chemotherapy and were randomized after completion of chemotherapy if they remained eligible and did not experience disease progression. The primary end point was investigator-assessed DFS.[28]

After a median follow-up of 32.2 months, atezolizumab treatment improved DFS compared with best supportive care in patients in the stage II to IIIA population whose tumors expressed PD-L1 on at least 1% of tumor cells (HR, 0.66; 95% CI, 0.50–0.88; P = .0039). At 24 months, the DFS rate was 74.6% for the atezolizumab group and 61.0% for the best supportive care group.

IMpower010 (NCT02486718) was a phase III, multicenter, open-label trial that randomly assigned 1,005 patients with surgically resected stage IB (tumor >4 cm) to stage IIIA NSCLC. Patients received atezolizumab (1,200 mg every 21 days intravenously) or best supportive care for 16 cycles or 1 year after standard adjuvant platinum-based chemotherapy. Patients were enrolled after resection if they were eligible for cisplatin-based chemotherapy and were randomized after completion of chemotherapy if they remained eligible and did not experience disease progression. The primary end point was investigator-assessed DFS.[28]

Atezolizumab also improved DFS in all patients in the stage II to IIIA population (HR, 0.79; 95% CI, 0.64–0.96; P = .020). At 24 months, the DFS rate was 70.2% for the atezolizumab group and 61.6% for the best supportive care group.

IMpower010 (NCT02486718) was a phase III, multicenter, open-label trial that randomly assigned 1,005 patients with surgically resected stage IB (tumor >4 cm) to stage IIIA NSCLC. Patients received atezolizumab (1,200 mg every 21 days intravenously) or best supportive care for 16 cycles or 1 year after standard adjuvant platinum-based chemotherapy. Patients were enrolled after resection if they were eligible for cisplatin-based chemotherapy and were randomized after completion of chemotherapy if they remained eligible and did not experience disease progression. The primary end point was investigator-assessed DFS.[28]

In the ITT population, which included patients with stage IB to IIIA disease, HRDFS was 0.81 (95% CI, 0.67–0.99; P = .040). However, the boundary for statistical significance for DFS was not crossed.

IMpower010 (NCT02486718) was a phase III, multicenter, open-label trial that randomly assigned 1,005 patients with surgically resected stage IB (tumor >4 cm) to stage IIIA NSCLC. Patients received atezolizumab (1,200 mg every 21 days intravenously) or best supportive care for 16 cycles or 1 year after standard adjuvant platinum-based chemotherapy. Patients were enrolled after resection if they were eligible for cisplatin-based chemotherapy and were randomized after completion of chemotherapy if they remained eligible and did not experience disease progression. The primary end point was investigator-assessed DFS.[28]

OS data are immature.

IMpower010 (NCT02486718) was a phase III, multicenter, open-label trial that randomly assigned 1,005 patients with surgically resected stage IB (tumor >4 cm) to stage IIIA NSCLC. Patients received atezolizumab (1,200 mg every 21 days intravenously) or best supportive care for 16 cycles or 1 year after standard adjuvant platinum-based chemotherapy. Patients were enrolled after resection if they were eligible for cisplatin-based chemotherapy and were randomized after completion of chemotherapy if they remained eligible and did not experience disease progression. The primary end point was investigator-assessed DFS.[28]

No new safety signals were noted.