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For Patients With Previously
Treated Metastatic
Non-Small
Cell Lung Cancer (NSCLC)

  • Full Indication

For Previously Treated Metastatic
Non-Squamous NSCLC

OPDIVO® Was Approved Based on Superior OS vs
Chemotherapy* in a Study Designed to Include PD-L1
Expressors and Non-Expressors1

*Docetaxel.

Checkmate 057: Overall Survival1,2


CHECKMATE 057 Overall Survival

Data shown here is from all the patients who underwent randomization and were included in efficacy analysis (intent-to-treat population).

See OS Figure for metastatic non-small cell lung cancer in the Full Prescribing Information for data on censored patients.

CI=confidence interval; HR=hazard ratio; mNSCLC=metastatic non-small cell lung cancer; ORR=overall response rate;
OS=overall survival; PD-1=programmed death receptor-1;
PD-L1=programmed death-ligand 1.


  • HR for OS=0.73 (95% CI: 0.60-0.89; P=0.0015). Median OS was 12.2 months
    (95% CI: 9.7-15.0) for OPDIVO and 9.4 months (95% CI: 8.0-10.7) for docetaxel1
  • ORR with OPDIVO was 19% (56/292; 4 complete responses [95% CI: 15-24]) vs 12% with docetaxel (36/290; 1 complete response [95% CI: 9-17; P=0.02]). The median duration of response was 17 months in the OPDIVO arm (95% CI: 8.4-NR) and 6 months in the docetaxel arm (95% CI: 4.4-7.0)1
  • Median PFS with OPDIVO was 2.3 months vs 4.2 months with docetaxel; HR=0.92,
    (95% CI: 0.77-1.11; P=0.39)1
  • Checkmate 057 results were based on the prespecified interim analysis conducted when 413 events (93% of the planned number of events for final analysis) were observed (190 in the OPDIVO arm and 223 in the docetaxel arm)1

Select Important Safety
Information

  • In Checkmate 017 and 057, serious adverse reactions occurred in 46% of patients receiving OPDIVO (n=418). The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and respiratory failure.
  • In Checkmate 017 and 057, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=418) were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite.

NR=not reached; PFS=progression-free survival.

OPDIVO Nearly Doubled OS vs Chemotherapy* for Patients Expressing PD-L1 at All Levels (≥1%)—Achieving an 8.1-Month Survival Advantage1†

Median Overall Survival Based on Prespecified Analysis by PD-L1 Expression1,2


CHECKMATE 057 Overall Survival

Median overall survival (OS) vs chemotherapy* by pre-specified PD-L1 expression level:

  • <5% (n=274): HR=1.01 (95% CI: 0.77–1.34); median OS=9.7 months with
    OPDIVO vs 10.1 months with chemotherapy1,2*
  • <10% (n=290): HR=1.00 (95% CI: 0.76–1.31); median OS=9.9 months with OPDIVO vs 10.3 months with chemotherapy1,2*

*Docetaxel.

Median overall survival in patients treated with OPDIVO who had a PD-L1 expression of ≥1%, ≥5%, or ≥10%.

Primary endpoint. All patients who underwent randomization were included in efficacy analysis (ITT=intent-to-treat-population).

§Based on a stratified proportional hazards model.

||Based on a stratified log-rank test.

P-value is compared with 0.0408 of the allocated alpha for this interim analysis.

#78% of patients had quantifiable PD-L1 expression (n=455/582). PD-L1 non-expressors were defined as <1% of tumor cells expressing PD-L1 (n=209) and PD-L1 expressors were defined as ≥1% of tumor cells expressing PD-L1 (n=246).

 

Select Important Safety
Information

  • In Checkmate 017 and 057, serious adverse reactions occurred in 46% of patients receiving OPDIVO (n=418). The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and respiratory failure.
  • In Checkmate 017 and 057, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=418) were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite.

Nivolumab (OPDIVO®) is a National Comprehensive Cancer Network® (NCCN®) Category 1 Recommended Therapy Option for Both Non-Squamous and Squamous Previously Treated Metastatic NSCLC.*

NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

*Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.6.2017. © National Comprehensive Cancer Network, Inc. 2017. All rights reserved. Accessed May 16, 2017. To view the most recent and complete version of the guidelines, go online to NCCN.org.

For Previously Treated Metastatic Squamous NSCLC Regardless of
PD-L1 Expression

OPDIVO® Is the Only PD-1 Inhibitor Approved Based on Superior Overall Survival vs Chemotherapy1,3-5*

*Docetaxel.

Checkmate 017: Overall Survival1,3


CHECKMATE 017 Overall Survival

See OS Figure for metastatic non-small cell lung cancer in the Full Prescribing Information for data on censored patients.

CI=confidence interval; HR=hazard ratio; mNSCLC=metastatic non-small cell lung cancer; OS=overall survival;
PD-1=programmed death receptor-1; PD-L1=programmed death-ligand 1.


  • OPDIVO demonstrated a 41% reduction in the risk of death compared to docetaxel3
  • ORR with OPDIVO was 20% (27/135; 1 complete response [95% CI: 14-28]) vs 9% with docetaxel (12/137; 0 complete responses [95% CI: 5-15; P=0.0083]). The median duration of response was NR in the OPDIVO arm (95% CI: 9.8-NR) and 8.4 months in the docetaxel arm (95% CI: 3.6-10.8)1
  • Median PFS with OPDIVO was 3.5 months vs 2.8 months with docetaxel; HR=0.62 (95% CI: 0.47-0.81; P=0.0004)1
  • Results were based on the prespecified interim analysis conducted when 199 events (86% of the planned number of events for final analysis) were observed (86 in the OPDIVO arm and 113 in the docetaxel arm)1
  • Checkmate 017 was a randomized (1:1), open-label, phase 3 study of OPDIVO 3 mg/kg IV over 60 minutes every 2 weeks (n=135) vs docetaxel 75 mg/m2 every 3 weeks (n=137). The primary endpoint was overall survival1
  • The study included patients regardless of PD-L1 status1

The recommended dose of OPDIVO is 240 mg administered as an intravenous infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity.

IV=intravenous; NR=not reached; PFS=progression-free survival.

Nivolumab (OPDIVO®) is a National Comprehensive Cancer Network® (NCCN®) Category 1 Recommended Therapy Option for Both Non-Squamous and Squamous Previously Treated Metastatic NSCLC.*

NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

*Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.6.2017. © National Comprehensive Cancer Network, Inc. 2017. All rights reserved. Accessed May 16, 2017. To view the most recent and complete version of the guidelines, go online to NCCN.org.

More Important Safety Information   Collapse  

Select Important Safety Information

OPDIVO is associated with the following Warnings and Precautions including immune-mediated: pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, skin adverse reactions, encephalitis, other adverse reactions; infusion reactions; and embryo-fetal toxicity.

Important Safety Information

Immune-Mediated Pneumonitis

  • OPDIVO can cause immune-mediated pneumonitis. Fatal cases have been reported. Monitor patients for signs with radiographic imaging and for symptoms of pneumonitis. Administer corticosteroids for Grade 2 or more severe pneumonitis. Permanently discontinue for Grade 3 or 4 and withhold until resolution for Grade 2. In patients receiving OPDIVO monotherapy, fatal cases of immune-mediated pneumonitis have occurred. Immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients.

Immune-Mediated Colitis

  • OPDIVO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO monotherapy for Grade 2 or 3 and permanently discontinue for Grade 4 or recurrent colitis upon re-initiation of OPDIVO. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients.

Immune-Mediated Hepatitis

  • OPDIVO can cause immune-mediated hepatitis. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater transaminase elevations. Withhold for Grade 2 and permanently discontinue for Grade 3 or 4 immune-mediated hepatitis. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients.

Immune-Mediated Endocrinopathies

  • OPDIVO can cause immune-mediated hypophysitis, immune-mediated adrenal insufficiency, autoimmune thyroid disorders, and Type 1 diabetes mellitus. Monitor patients for signs and symptoms of hypophysitis, signs and symptoms of adrenal insufficiency, thyroid function prior to and periodically during treatment, and hyperglycemia. Administer hormone replacement as clinically indicated and corticosteroids for Grade 2 or greater hypophysitis. Withhold for Grade 2 or 3 and permanently discontinue for Grade 4 hypophysitis. Administer corticosteroids for Grade 3 or 4 adrenal insufficiency. Withhold for Grade 2 and permanently discontinue for Grade 3 or 4 adrenal insufficiency. Administer hormone-replacement therapy for hypothyroidism. Initiate medical management for control of hyperthyroidism. Withhold OPDIVO for Grade 3 and permanently discontinue for Grade 4 hyperglycemia.
  • In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients. In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994) of patients. In patients receiving OPDIVO monotherapy, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 9% (171/1994) of patients. Hyperthyroidism occurred in 2.7% (54/1994) of patients receiving OPDIVO monotherapy. In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients.

Immune-Mediated Nephritis and Renal Dysfunction

  • OPDIVO can cause immune-mediated nephritis. Monitor patients for elevated serum creatinine prior to and periodically during treatment. Administer corticosteroids for Grades 2-4 increased serum creatinine. Withhold OPDIVO for Grade 2 or 3 and permanently discontinue for Grade 4 increased serum creatinine. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients.

Immune-Mediated Skin Adverse Reactions

  • OPDIVO can cause immune-mediated rash, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), some cases with fatal outcome. Administer corticosteroids for Grade 3 or 4 rash. Withhold for Grade 3 and permanently discontinue for Grade 4 rash. For symptoms or signs of SJS or TEN, withhold OPDIVO and refer the patient for specialized care for assessment and treatment; if confirmed, permanently discontinue. In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients.

Immune-Mediated Encephalitis

  • OPDIVO can cause immune-mediated encephalitis. Evaluation of patients with neurologic symptoms may include, but not be limited to, consultation with a neurologist, brain MRI, and lumbar puncture. Withhold OPDIVO in patients with new-onset moderate to severe neurologic signs or symptoms and evaluate to rule out other causes. If other etiologies are ruled out, administer corticosteroids and permanently discontinue OPDIVO for immune-mediated encephalitis. In patients receiving OPDIVO monotherapy, encephalitis occurred in 0.2% (3/1994) of patients. Fatal limbic encephalitis occurred in one patient after 7.2 months of exposure despite discontinuation of OPDIVO and administration of corticosteroids.

Other Immune-Mediated Adverse Reactions

  • Based on the severity of adverse reaction, permanently discontinue or withhold treatment, administer high-dose corticosteroids, and, if appropriate, initiate hormone-replacement therapy. Across clinical trials of OPDIVO the following clinically significant immune-mediated adverse reactions occurred in <1.0% of patients receiving OPDIVO: uveitis, iritis, pancreatitis, facial and abducens nerve paresis, demyelination, polymyalgia rheumatica, autoimmune neuropathy, Guillain-Barré syndrome, hypopituitarism, systemic inflammatory response syndrome, gastritis, duodenitis, sarcoidosis, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), myositis, myocarditis, rhabdomyolysis, motor dysfunction, vasculitis, and myasthenic syndrome.

Infusion Reactions

  • OPDIVO can cause severe infusion reactions, which have been reported in <1.0% of patients in clinical trials. Discontinue OPDIVO in patients with Grade 3 or 4 infusion reactions. Interrupt or slow the rate of infusion in patients with Grade 1 or 2. In patients receiving OPDIVO monotherapy, infusion-related reactions occurred in 6.4% (127/1994) of patients.

Embryo-Fetal Toxicity

  • Based on its mechanism of action, OPDIVO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with an OPDIVO-containing regimen and for at least 5 months after the last dose of OPDIVO.

Lactation

  • It is not known whether OPDIVO is present in human milk. Because many drugs, including antibodies, are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from an OPDIVO-containing regimen, advise women to discontinue breastfeeding during treatment.

Serious Adverse Reactions

  • In Checkmate 017 and 057, serious adverse reactions occurred in 46% of patients receiving OPDIVO (n=418). The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and respiratory failure.

Common Adverse Reactions

  • In Checkmate 017 and 057, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=418) were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite.

Please see U.S. Full Prescribing Information for OPDIVO.

References:

  1. OPDIVO [package insert]. Princeton, NJ: Bristol‑Myers Squibb Company; 2017.
  2. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373:1627-1639.
  3. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373:123-135.
  4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.6.2017. © National Comprehensive Cancer Network, Inc. 2017. All rights reserved. Accessed May 16, 2017. To view the most recent and complete version of the guideline, go online to NCCN.org.
  5. AlphaImpact Rx BrandImpact Treatment Report. Week Ending 9-11-2015.
  6. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373(17):1627-1639 [supplementary appendix].
  7. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373(2):123-125 [supplementary appendix].
  8. Wang C, Thudium KB, Han M, et al. In vitro characterization of the anti-PD-1 antibody nivolumab, BMS-936558, and in vivo toxicology in non-human primates. Cancer Immunol Res. 2014;2(9):846-856.