Four and a Half Years On: Long-Term Outcomes of the First Cohort of Lung Cancer Patients Treated with Opdivo

On July 4, 2014, Opdivo (nivolumab injection, commonly known as "O Drug") was approved in Japan, becoming the first PD-1 inhibitor to gain regulatory approval worldwide. This marked the beginning of its remarkable journey. To date, the U.S. Food and Drug Administration (FDA) has approved 17 indications for Opdivo, covering nine types of cancer, including lung cancer (non-small cell lung cancer and small cell lung cancer), melanoma, renal cell carcinoma, Hodgkin lymphoma, head and neck squamous cell carcinoma, bladder cancer, colorectal cancer, hepatocellular carcinoma, and gastric cancer. It has become the PD-1 inhibitor with the most approved indications.

It has been four and a half years since the launch of Opdivo. How are the first batch of patients who used Opdivo doing? Let’s take a look at the AACR report.

As a blockbuster drug from Bristol-Myers Squibb Company, the long-term survival outcomes of Opdivo as a second-line therapy for patients with non-small cell lung cancer (NSCLC) were presented at the 2019 AACR Annual Meeting. The data pooled four large clinical studies (CheckMate-017, CheckMate-057, CheckMate-063, and CheckMate-003), enrolling a total of 664 patients. The study investigated the efficacy of Opdivo in treating previously treated advanced NSCLC patients.

Trial Introduction

CheckMate 017 and CheckMate 057 were both Phase III clinical trials of Opdivo versus docetaxel for the treatment of advanced non-small cell lung cancer (NSCLC) after failure of first-line chemotherapy, targeting patients with squamous cell carcinoma and non-squamous cell carcinoma, respectively.

CheckMate-063 was a phase II study evaluating the efficacy of Opdivo in patients with metastatic squamous non-small cell lung cancer who had experienced disease progression after receiving at least two prior lines of therapy, with 65% of patients having received three or more prior lines of treatment.

The CheckMate-003 study is a multicenter, Phase I, dose-escalation expanded cohort study. One of the objectives of the trial was to evaluate the 5-year overall survival of Opdivo in previously treated NSCLC patients, with overall survival as the exploratory endpoint.

Summary Analysis of Results

In a pooled analysis of the results from four clinical trials, patients treated with Opdivo (O drug) achieved a 4-year overall survival (OS) rate of 14%, compared to 5% for those receiving chemotherapy (docetaxel). Subgroup analysis revealed that among patients with PD-L1 expression ≥1%, the 4-year survival rate increased by 5 percentage points to 19%. Notably, even in the subgroup with PD-L1 expression <1%, the 4-year survival rate reached 11%.<>

Further exploratory analysis of overall survival revealed that among patients who achieved a complete or partial response at 6 months, 58% of those treated with Opdivo were still alive after four years, compared to only 12% of those treated with docetaxel.

Among patients with stable disease at 6 months, 19% of those treated with Opdivo survived after four years, compared to only 2% of those treated with docetaxel.

Safety

Across all four clinical studies, the long-term safety data for Opdivo were consistent with known adverse events, and no new safety signals were identified. The discontinuation rate due to treatment-related adverse events among patients receiving Opdivo was 8.7%. The most common treatment-related adverse event was fatigue (reported in 21.7% of patients).

Significance

It is generally believed that the efficacy of Opdivo or Keytruda (pembrolizumab) is suboptimal in patients with low tumor mutational burden (TMB) or low PD-1/PD-L1 expression. However, this pooled analysis demonstrated that the 4-year survival rate reached 11% even in the subgroup of patients with PD-L1 expression <1%.

Dr. Sabine Maier, Head of Thoracic Oncology Development at Bristol-Myers Squibb, stated: “We observed very compelling survival curves in these pooled analyses. Compared with individual studies, such pooled analyses enable a more comprehensive understanding of patients’ long-term survival and provide new insights into the value of nivolumab injection as second-line therapy for lung cancer. These data will further reinforce our long-term commitment to the field of cancer treatment, helping patients with urgent unmet needs achieve more durable therapeutic outcomes.”

Opdivo has already been approved in China for the treatment of NSCLC. The release of these long-term efficacy results is of significant importance to Chinese lung cancer patients. While the incidence of lung cancer is high, its 5-year survival rate remains only around 5%. For advanced-stage NSCLC, a 4-year survival rate of 14% represents a very favorable outcome.

We extend our gratitude to the tireless scientists, the innovative pharmaceutical companies, and the regulatory authorities who courageously assume risks. It is their reverence for life that has brought countless hopes of survival to cancer 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.

Source: CPhI Pharmaceutical Online Author: Ye Fenghong