Nivolumab plus platinum-based chemotherapy

CheckMate 816 (NCT02998528) was a phase III open-label trial that enrolled 358 patients with resectable stage IB to stage IIIA NSCLC. Notably, patients with stage IB disease had tumors measuring at least 4 cm and were classified according to the American Joint Committee on Cancer (AJCC) 7th edition staging criteria used for this trial; these tumors are now classified as stage IIA according to the AJCC 8th edition staging criteria. Patients were randomly assigned to receive nivolumab (360 mg) in combination with platinum-doublet chemotherapy or platinum-doublet chemotherapy alone every 3 weeks for three cycles before undergoing definitive surgery. The primary end points were EFS (defined as the time from randomization to any progression of disease precluding surgery, progression or recurrence of disease after surgery, progression of disease in the absence of surgery, or death from any cause) and pathological complete response (defined as 0% residual viable tumor cells in the primary tumor and sampled lymph nodes) according to blinded independent central review.[10][Level of evidence B1]

CheckMate 816 (NCT02998528) was a phase III open-label trial that enrolled 358 patients with resectable stage IB to stage IIIA NSCLC. Notably, patients with stage IB disease had tumors measuring at least 4 cm and were classified according to the American Joint Committee on Cancer (AJCC) 7th edition staging criteria used for this trial; these tumors are now classified as stage IIA according to the AJCC 8th edition staging criteria. Patients were randomly assigned to receive nivolumab (360 mg) in combination with platinum-doublet chemotherapy or platinum-doublet chemotherapy alone every 3 weeks for three cycles before undergoing definitive surgery. The primary end points were EFS (defined as the time from randomization to any progression of disease precluding surgery, progression or recurrence of disease after surgery, progression of disease in the absence of surgery, or death from any cause) and pathological complete response (defined as 0% residual viable tumor cells in the primary tumor and sampled lymph nodes) according to blinded independent central review.[10][Level of evidence B1]

With a minimum follow-up of 21 months, the median EFS was 31.6 months (95% CI, 30.2–not reached [NR]) in the nivolumab-plus-chemotherapy group and 20.8 months (95% CI, 14.0–26.7) in the chemotherapy-alone group (HR, 0.63; 97.38% CI, 0.43–0.91; P = .005).

CheckMate 816 (NCT02998528) was a phase III open-label trial that enrolled 358 patients with resectable stage IB to stage IIIA NSCLC. Notably, patients with stage IB disease had tumors measuring at least 4 cm and were classified according to the American Joint Committee on Cancer (AJCC) 7th edition staging criteria used for this trial; these tumors are now classified as stage IIA according to the AJCC 8th edition staging criteria. Patients were randomly assigned to receive nivolumab (360 mg) in combination with platinum-doublet chemotherapy or platinum-doublet chemotherapy alone every 3 weeks for three cycles before undergoing definitive surgery. The primary end points were EFS (defined as the time from randomization to any progression of disease precluding surgery, progression or recurrence of disease after surgery, progression of disease in the absence of surgery, or death from any cause) and pathological complete response (defined as 0% residual viable tumor cells in the primary tumor and sampled lymph nodes) according to blinded independent central review.[10][Level of evidence B1]

The estimated percentage of patients surviving without disease progression or disease recurrence at 1 year was 76.1% for patients who received nivolumab plus chemotherapy and 63.4% for patients who received chemotherapy alone. The magnitude of benefit was greater in 1) patients with stage IIIA disease versus patients with stage IB or II disease (HR, 0.54; 95% CI, 0.37–0.80 vs. HR, 0.87; 95% CI, 0.48–1.56), 2) patients with tumor programmed death-ligand 1 (PD-L1) expression ≥1% versus <1% (HR, 0.41; 95% CI, 0.24–0.70 vs. HR, 0.85; 95% CI, 0.54–1.32), and 3) patients with nonsquamous histology versus squamous histology.

CheckMate 816 (NCT02998528) was a phase III open-label trial that enrolled 358 patients with resectable stage IB to stage IIIA NSCLC. Notably, patients with stage IB disease had tumors measuring at least 4 cm and were classified according to the American Joint Committee on Cancer (AJCC) 7th edition staging criteria used for this trial; these tumors are now classified as stage IIA according to the AJCC 8th edition staging criteria. Patients were randomly assigned to receive nivolumab (360 mg) in combination with platinum-doublet chemotherapy or platinum-doublet chemotherapy alone every 3 weeks for three cycles before undergoing definitive surgery. The primary end points were EFS (defined as the time from randomization to any progression of disease precluding surgery, progression or recurrence of disease after surgery, progression of disease in the absence of surgery, or death from any cause) and pathological complete response (defined as 0% residual viable tumor cells in the primary tumor and sampled lymph nodes) according to blinded independent central review.[10][Level of evidence B1]

Pathological complete response was observed in 24% (95% CI, 18.0%– 31.0%) of patients who received nivolumab plus chemotherapy and 2.2% (95% CI, 0.6%–5.6%) of patients who received chemotherapy alone (odds ratio, 13.94; 99% CI, 3.49–55.75; P < .001).

CheckMate 816 (NCT02998528) was a phase III open-label trial that enrolled 358 patients with resectable stage IB to stage IIIA NSCLC. Notably, patients with stage IB disease had tumors measuring at least 4 cm and were classified according to the American Joint Committee on Cancer (AJCC) 7th edition staging criteria used for this trial; these tumors are now classified as stage IIA according to the AJCC 8th edition staging criteria. Patients were randomly assigned to receive nivolumab (360 mg) in combination with platinum-doublet chemotherapy or platinum-doublet chemotherapy alone every 3 weeks for three cycles before undergoing definitive surgery. The primary end points were EFS (defined as the time from randomization to any progression of disease precluding surgery, progression or recurrence of disease after surgery, progression of disease in the absence of surgery, or death from any cause) and pathological complete response (defined as 0% residual viable tumor cells in the primary tumor and sampled lymph nodes) according to blinded independent central review.[10][Level of evidence B1]

Median OS was not reached in either group (HRdeath, 0.57; 99.67% CI, 0.30–1.07; P = .008).

CheckMate 816 (NCT02998528) was a phase III open-label trial that enrolled 358 patients with resectable stage IB to stage IIIA NSCLC. Notably, patients with stage IB disease had tumors measuring at least 4 cm and were classified according to the American Joint Committee on Cancer (AJCC) 7th edition staging criteria used for this trial; these tumors are now classified as stage IIA according to the AJCC 8th edition staging criteria. Patients were randomly assigned to receive nivolumab (360 mg) in combination with platinum-doublet chemotherapy or platinum-doublet chemotherapy alone every 3 weeks for three cycles before undergoing definitive surgery. The primary end points were EFS (defined as the time from randomization to any progression of disease precluding surgery, progression or recurrence of disease after surgery, progression of disease in the absence of surgery, or death from any cause) and pathological complete response (defined as 0% residual viable tumor cells in the primary tumor and sampled lymph nodes) according to blinded independent central review.[10][Level of evidence B1]

Grade 3 or 4 treatment-related adverse events occurred in 33.5% of patients in the nivolumab-plus-chemotherapy group and in 36.9% of patients in the chemotherapy-alone group. Treatment-related adverse events led to treatment discontinuation in 10.2% of patients in the nivolumab-plus-chemotherapy group and in 9.7% of patients in the chemotherapy-alone group.

NADIM (NCT03081689) was an open-label, multicenter, single-arm trial for patients with stage IIIA NSCLC with surgically resectable disease. Patients received neoadjuvant paclitaxel and carboplatin plus nivolumab (360 mg) every 21 days for three cycles, followed by adjuvant nivolumab monotherapy for 1 year (240 mg once every 2 weeks for 4 months, followed by 480 mg once every 4 weeks for 8 months). The intention-to-treat (ITT) population included all patients who received neoadjuvant treatment. The per-protocol population included all patients who underwent tumor resection and received at least one cycle of adjuvant therapy. The median follow-up time was 60 months.[11,12]Circulating tumor DNA (ctDNA) from plasma samples obtained before and after neoadjuvant treatment (but before surgery) was analyzed with the hybridization capture–based TruSight Oncology 500 ctDNA next-generation sequencing assay on a NovaSeq sequencer (Illumina).

NADIM (NCT03081689) was an open-label, multicenter, single-arm trial for patients with stage IIIA NSCLC with surgically resectable disease. Patients received neoadjuvant paclitaxel and carboplatin plus nivolumab (360 mg) every 21 days for three cycles, followed by adjuvant nivolumab monotherapy for 1 year (240 mg once every 2 weeks for 4 months, followed by 480 mg once every 4 weeks for 8 months). The intention-to-treat (ITT) population included all patients who received neoadjuvant treatment. The per-protocol population included all patients who underwent tumor resection and received at least one cycle of adjuvant therapy. The median follow-up time was 60 months.[11,12]Circulating tumor DNA (ctDNA) from plasma samples obtained before and after neoadjuvant treatment (but before surgery) was analyzed with the hybridization capture–based TruSight Oncology 500 ctDNA next-generation sequencing assay on a NovaSeq sequencer (Illumina).

In the ITT population, the 5-year PFS rate was 65.0% (95% CI, 49.4%–76.9%), and the OS rate was 69.3% (53.7%–80.6%).[12][Level of evidence C1]

NADIM (NCT03081689) was an open-label, multicenter, single-arm trial for patients with stage IIIA NSCLC with surgically resectable disease. Patients received neoadjuvant paclitaxel and carboplatin plus nivolumab (360 mg) every 21 days for three cycles, followed by adjuvant nivolumab monotherapy for 1 year (240 mg once every 2 weeks for 4 months, followed by 480 mg once every 4 weeks for 8 months). The intention-to-treat (ITT) population included all patients who received neoadjuvant treatment. The per-protocol population included all patients who underwent tumor resection and received at least one cycle of adjuvant therapy. The median follow-up time was 60 months.[11,12]Circulating tumor DNA (ctDNA) from plasma samples obtained before and after neoadjuvant treatment (but before surgery) was analyzed with the hybridization capture–based TruSight Oncology 500 ctDNA next-generation sequencing assay on a NovaSeq sequencer (Illumina).

Major pathological response was defined as the presence of 10% or fewer tumor cells in the primary tumor. A total of 82.9% of patients had a major pathological response, including 63.4% of patients who had a complete pathological response. A total of 17.1% patients had an incomplete response.

NADIM (NCT03081689) was an open-label, multicenter, single-arm trial for patients with stage IIIA NSCLC with surgically resectable disease. Patients received neoadjuvant paclitaxel and carboplatin plus nivolumab (360 mg) every 21 days for three cycles, followed by adjuvant nivolumab monotherapy for 1 year (240 mg once every 2 weeks for 4 months, followed by 480 mg once every 4 weeks for 8 months). The intention-to-treat (ITT) population included all patients who received neoadjuvant treatment. The per-protocol population included all patients who underwent tumor resection and received at least one cycle of adjuvant therapy. The median follow-up time was 60 months.[11,12]Circulating tumor DNA (ctDNA) from plasma samples obtained before and after neoadjuvant treatment (but before surgery) was analyzed with the hybridization capture–based TruSight Oncology 500 ctDNA next-generation sequencing assay on a NovaSeq sequencer (Illumina).

Disease progression occurred in 11 patients (24%).

NADIM (NCT03081689) was an open-label, multicenter, single-arm trial for patients with stage IIIA NSCLC with surgically resectable disease. Patients received neoadjuvant paclitaxel and carboplatin plus nivolumab (360 mg) every 21 days for three cycles, followed by adjuvant nivolumab monotherapy for 1 year (240 mg once every 2 weeks for 4 months, followed by 480 mg once every 4 weeks for 8 months). The intention-to-treat (ITT) population included all patients who received neoadjuvant treatment. The per-protocol population included all patients who underwent tumor resection and received at least one cycle of adjuvant therapy. The median follow-up time was 60 months.[11,12]Circulating tumor DNA (ctDNA) from plasma samples obtained before and after neoadjuvant treatment (but before surgery) was analyzed with the hybridization capture–based TruSight Oncology 500 ctDNA next-generation sequencing assay on a NovaSeq sequencer (Illumina).

A total of 14 patients (30%) died, including 9 (20%) of disease relapse and 5 (11%) of causes not related to the tumor.

NADIM (NCT03081689) was an open-label, multicenter, single-arm trial for patients with stage IIIA NSCLC with surgically resectable disease. Patients received neoadjuvant paclitaxel and carboplatin plus nivolumab (360 mg) every 21 days for three cycles, followed by adjuvant nivolumab monotherapy for 1 year (240 mg once every 2 weeks for 4 months, followed by 480 mg once every 4 weeks for 8 months). The intention-to-treat (ITT) population included all patients who received neoadjuvant treatment. The per-protocol population included all patients who underwent tumor resection and received at least one cycle of adjuvant therapy. The median follow-up time was 60 months.[11,12]Circulating tumor DNA (ctDNA) from plasma samples obtained before and after neoadjuvant treatment (but before surgery) was analyzed with the hybridization capture–based TruSight Oncology 500 ctDNA next-generation sequencing assay on a NovaSeq sequencer (Illumina).

Tumor mutational burden and PD-L1 status were not predictive of survival.

NADIM (NCT03081689) was an open-label, multicenter, single-arm trial for patients with stage IIIA NSCLC with surgically resectable disease. Patients received neoadjuvant paclitaxel and carboplatin plus nivolumab (360 mg) every 21 days for three cycles, followed by adjuvant nivolumab monotherapy for 1 year (240 mg once every 2 weeks for 4 months, followed by 480 mg once every 4 weeks for 8 months). The intention-to-treat (ITT) population included all patients who received neoadjuvant treatment. The per-protocol population included all patients who underwent tumor resection and received at least one cycle of adjuvant therapy. The median follow-up time was 60 months.[11,12]Circulating tumor DNA (ctDNA) from plasma samples obtained before and after neoadjuvant treatment (but before surgery) was analyzed with the hybridization capture–based TruSight Oncology 500 ctDNA next-generation sequencing assay on a NovaSeq sequencer (Illumina).

Low pretreatment levels of ctDNA were significantly associated with improved PFS (HR, 0.20; 95% CI, 0.06–0.63) and OS (HR, 0.07; 95% CI, 0.01–0.39).

NADIM (NCT03081689) was an open-label, multicenter, single-arm trial for patients with stage IIIA NSCLC with surgically resectable disease. Patients received neoadjuvant paclitaxel and carboplatin plus nivolumab (360 mg) every 21 days for three cycles, followed by adjuvant nivolumab monotherapy for 1 year (240 mg once every 2 weeks for 4 months, followed by 480 mg once every 4 weeks for 8 months). The intention-to-treat (ITT) population included all patients who received neoadjuvant treatment. The per-protocol population included all patients who underwent tumor resection and received at least one cycle of adjuvant therapy. The median follow-up time was 60 months.[11,12]Circulating tumor DNA (ctDNA) from plasma samples obtained before and after neoadjuvant treatment (but before surgery) was analyzed with the hybridization capture–based TruSight Oncology 500 ctDNA next-generation sequencing assay on a NovaSeq sequencer (Illumina).

Undetectable ctDNA levels after neoadjuvant treatment were significantly associated with PFS (HR, 0.26; 95% CI, 0.07–0.93) and OS (HR, 0.04; 95% CI, 0.00–0.55).