How are the First Lung Cancer Patients Treated with Opdivo 4.5 Years Later?

Since Opdivo (Nivolumab Injection, commonly known as O Drug) was approved in Japan on July 4, 2014 to become the world’s first PD-1 inhibitor approved by a regulator, it has started its unbelievable road, and has so far been approved 17 indications by the FDA, involving lung cancer (non-small cell lung cancer (NSCLC) and small cell lung cancer), melanoma, renal cell carcinoma, Hodgkin's lymphoma, head and neck squamous cell carcinoma, bladder cancer, colorectal cancer, liver cancer, and gastric cancer, to become the PD-1 inhibitor with the most indications approved.

It has been 4.5 years since Opdivo was marketed. Then, how are the first patients treated with Opdivo? Let’s check the report at the AACR Annual Meeting.

As a blockbuster drug of BMS, the long-term survival outcomes of Opdivo’s treating NSCLC patients as a second-line therapy were announced at the AACR Annual Meeting 2019. The data summarize the four large clinical studies (CheckMate-017, CheckMate-057, CheckMate-063, and CheckMate-003) that enrolled 664 patients in total and explored the effects of treating previously-treated advanced NSCLC patients with Opdivo.

About the trials

CheckMate 017 and CheckMate 057 separately targeted squamous and non-squamous patients, and both were Phase III clinical trial of Opdivo compared to docetaxel in advanced NSCLC patients after failure of a line of chemotherapy.

CheckMate-063 was a Phase II study that assessed the efficacy of Opdivo in patients with metastatic squamous NSCLC who had disease progression after receiving at least 2 lines of prior therapy and 65% of who have received 3 or more lines of therapy.

CheckMate-003 was a Phase I, multicenter, dose-escalation cohort expansion study, and one of its purposes was to assess the five-year overall survival in Opdivo-treated patients with previously-treated NSCLC, with the exploratory endpoint being the overall survival.

Outcomes summary and analysis

In the pooled analysis of the four clinical trials, the overall survival (OS) of Opdivo-treated patients at four years reached 14%, compared to 5% for chemotherapy (docetaxel)-treated patients. According to subgroup analysis, the four-year OS in patients with PD-L1 ≥1% increased by 5% to reach 19%. Notably, in patients with PD-L1 <1%, the four-year OS also reached 11%.

Additionally, an exploratory landmark analysis of OS found that of patients who had a complete or partial response at six months, 58% of those treated with Opdivo were alive four years later vs. 12% of patients treated with docetaxel.

Of patients who had stable disease at six months, 19% of those treated with Opdivo were alive four years later vs. 2% of patients treated with docetaxel.

Safety

Long-term safety data for Opdivo from all the four clinical studies were consistent with the known adverse event profile and did not reveal any new safety signals. The discontinuation rate due to treatment-related adverse events (AEs) was 8.7% in patients treated with Opdivo. The most common treatment-related AE was fatigue (in 21.7% of patients).

Significance

It is generally considered that the efficacy of using Opdivo or Keytruda will not be ideal when the TMB (tumor mutation burden) or PD-1/L1 expression is not high, however, this pooled analysis shows that the four-year OS in patients with PD-L1<1% also reached 11%.

Sabine Maier, M.D., development lead, thoracic cancers, BMS, said, "The positive survival curve observed in these pooled analyses offers a more holistic view of long-term survival outcomes than what we’ve seen in the individual studies and provides new insights into the value Opdivo can provide for lung cancer patients in the second-line setting. These data also serve to reinforce our longstanding commitment to delivering cancer therapies that may offer more durable responses for patients in critical need."

Opdivo has been approved in China to treat NSCLC. This announcement of the long-term efficacy results is of great significance to Chinese lung cancer patients. Lung cancer has a high incidence, however, the five-year OS is only 5%. The four-year OS of 14% was quite a good result for advanced NSCLC patients.

We must thank the tireless scientists, innovative pharmaceutical enterprises, and risk-taking regulators. It is because of their awe of life that has brought a myriad of hopes of life to tumor patients.

References:

1. https://news.bms.com/press-release/corporatefinancial-news/bristol-myers-squibb-announces-long-term-survival-results-pool;

2. Bristol-Myers Squibb Announces Long-Term Survival Results from Pooled Analyses of Opdivo(nivolumab) in Previously-Treated Non-Small Cell Lung Cancer Patients.Retrieved April 3, 2019.

About  the Author:    

Yefenghong

Ye  Fenghong, a medical editor specializing in oncology at a healthcare internet  company, has conducted in-depth research on the pathogenesis and clinical  treatment of lung cancer and breast cancer. She has previously been involved  in the design and synthesis of anti-tumor drugs and has some experience in  computer-aided drug design. She is currently devoted to introducing  cutting-edge cancer treatment drugs to a wide range of readers, aiming to  help more people avoid cancer pain and embrace good health.    

-----------------------------------------------------------------------
Editor's Note:

To apply for becoming a contributor of En-CPhI.cn,

welcome to send your CV and sample works to us,

Email: Julia.Zhang@ubmsinoexpo.com.