Broome Oncology

Superior Overall Survival for Opdivo (nivolumab) Plus Low-Dose Yervoy (ipilimumab) compared Chemotherapy in Advanced Non-Small Cell Lung Cancer

The Opdivo plus low-dose Yervoy immunotherapy combination improved long-term survival for patients with advanced non-small cell lung cancer (NSCLCC) across PD-L1 expression levels. (3)

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. (4,5)

About CheckMate -227

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 alone in patients with non-squamous and squamous lung cancers expressing PD-L1.

The trial results released in September 2019 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.  In patients with PD-L1 <1%, the median duration of response was 18 months for the combination compared to 4.8 months for chemotherapy.

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 has the potential to deliver deep and durable responses, with a clear survival benefit, in first-line non-small cell lung cancer irrespective of PD-L1 expression.

References:

3 https://news.bms.com/press-release/bms/bristol-myers-squibb-announces-final-results-checkmate-227-part-1-demonstrating-su

4 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.

5 16th World Conference on Lung Cancer. Abstract #786.

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