by Dr. C.H. Weaver M.D. updated 5/2020
The immunotherapy drug Opdivo (nivolumab) plays a role in the management of non-small cell lung cancer (NSCLC) both as initial treatment of advanced disease and in patients with recurrent cancer.
- Opdivo® has been compared to the chemotherapy agent Taxotere (docetaxel) for the treatment of recurrent NSCLC in several pivotal clinical trials - each confirming that Opdivo produces superior survival duration. (1-3)
- Opdivo plus low-dose Yervoy immunotherapy has been shown to improve long-term survival for patients with advanced NSCLC when used as initial treatment across PD-L1 expression levels, (4) and approved by the FDA in May 2020. (8)
Opdivo is a checkpoint inhibitor precision cancer medicine that helps the patient’s immune system to fight the cancer cells. Opdivo blocks a molecule referred to as PD-1, which is involved in suppressing the immune system’s ability to fight cancer cells. By blocking the effects of PD-1, Opdivo restores the immune system’s ability to recognize and attack cancer cells.
Opdivo is approved by the United States Food and Drug Administration (FDA) for the treatment of both squamous and non-squamous NSCLC.
All patients with lung cancer should undergo genomic biomarker testing for PD-L1, PD-1, epidermal growth factor receptor (EGFR) and other biomarkers as part of their initial evaluation. The number of precision cancer medicines available to treat NSCLC is evolving and their use can avoid chemotherapy use in many individuals and improve treatment outcomes. Using immunotherapy in EGFR + NSCLC can cause serious side effects.
Opdivo Plus Low-Dose Yervoy (ipilimumab) as Initial Treatment for Advanced NSCLC
Both Opdivo and Yervoy are effective for the treatment of many cancers including NSCLC. These drugs are designed to help the immune system recognize and fight cancer. Opdivo belongs to a class of medicines called PD-1 inhibitors, which block the protein PD-1. PD-1 inhibits certain types of immune responses. Yervoy, is a monoclonal antibody that targets a molecule known as CTLA4. CTLA4 is found on the surface of T cells (a type of immune cell) and is thought to inhibit immune responses. Researchers theorized that blocking PD-1 and CTLA4 together may improve the immune system’s ability to fight cancer and this was confirmed in a Phase I study, called CheckMate -012. (5,6)
The CheckMate-227 clinical trial evaluated the first line treatment of advanced NSCLC with the immunotherapy combination of Opdivo plus low-dose Yervoy or Opdivo alone compared to chemotherapy in patients with non-squamous and squamous NSCLC expressing PD-L1.
The trial results were updated in May 2020 and revealed that the two-year survival rate for patients treated with the immunotherapy combination regimen was 40% for patients irrespective of PD-L1 expression compared to only 23% for treatment with chemotherapy alone. With a minimum follow-up of 29.3 months the median duration of response to treatment for the combination therapy arm was 23.2 months compared to only 6.2 months for chemotherapy.
The most common reported side effects by patients receiving the combination of nivolumab plus were fatigue, rash, decreased appetite, musculoskeletal pain, diarrhea/colitis, dyspnea, cough, pruritis, nausea, and hepatitis.
The trial also evaluated the importance of tumor mutational burden (TMB): patients with TMB ≥10 mut/Mb across the PD-L1 spectrum experienced improved overall survival with the Opdivo - Yervoy combination or Opdivo alone compared to chemotherapy in NSCLC patients whose tumors express PD-L1 ≥1%.
Checkmate 227 clearly demonstrates that dual Immunotherapy with Opdivo + Yervoy has the potential to deliver deep and durable responses, with a clear survival benefit as treatment for first-line NSCLC irrespective of PD-L1 expression.
Recurrent NSCLC - Checkmate 057
The goal of treatment of recurrent non-small cell lung cancer (NSCLC) has historically been to control symptoms, improve quality of life and prolong survival.
Updated pooled analyses of the CheckMate 017 and 057 clinical trials comparing Opdivo with Taxotere was presented at the International Association for the Study of Lung Cancer World Conference on Lung Cancer in September 2019 and showed that 13.4% of Opdivo treated patients survived 5 years compared with only 2.6% of patients treated with Taxotere. The benefit occurred among both squamous and non-squamous NSCLC.
The median duration of response for Opdivo was 19.9 months and 5.6 months with docetaxel. At 5 years, 32.2% of responders remained in response with Opdivo.
Checkmate 057 included nearly 600 patients with advanced non-squamous NSCLC that had stopped responding to prior platinum-based chemotherapy. Patients were treated with either Opdivo or docetaxel and were directly compared.
- Median overall survival was over a year (12.2) months for patients treated with Opdivo, compared with 9.4 months for those treated with docetaxel.
- At one year, the overall survival rate was 51% among patients treated with Opdivo, compared with 39% among those treated with docetaxel.
- At 18 months, survival was 39% for patients treated with Opdivo, compared with 23% for those treated with docetaxel.
- Patients with higher levels of the PD-1 ligand demonstrated even greater improvements in outcomes with Opdivo, compared to those without elevated PD-1 ligand levels.
- Serious side effects were reported in 10% of patients treated with Opdivo, compared with 54% of those treated with docetaxel.
The checkMate 017 clinical trial also showed a significantly superior survival rate of 42% versus 24% for Opdivo compared to Taxotere in patients with squamous NSCLC.
The CheckMate 063 clinical trial included patients with metastatic squamous cell NSCLC who had progressed after receiving a platinum-based therapy and at least one additional systemic treatment regimen. In this trial, Opdivo showed an estimated 18-month OS rate of 27%. At 18 months, confirmed objective response rate—the study’s primary endpoint—was 15%. Median OS was 8.1 months and the therapy was well tolerated.
- Gettinger S, et al. Abstract OA14.04. Presented at: International Association for the Study of Lung Cancer World Conference on Lung Cancer; Sept. 7-10, 2019; Barcelona.
- Bristol-Meyers Squibb Press Release
- Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer. New England Journal of Medicine. 2015; 373:1627-1639.
- Bristol-Myers Squibb Announces Final Results from CheckMate -227 Part 1 Demonstrating Superior Overall Survival for Opdivo (nivolumab) Plus Low-Dose Yervoy (ipilimumab) vs. Chemotherapy in Advanced Non-Small Cell Lung Cancer
- Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. New England Journal of Medicine [early online publication]. May 31, 2015.
- 16th World Conference on Lung Cancer. Abstract #786.
- FDA approves nivolumab plus ipilimumab for first-line mNSCLC (PD-L1 tumor expression ≥1%)