Bristol Myers Squibb Receives Positive CHMP Opinion Recommending Opdivo (nivolumab) as Second-Line Treatment for Unresectable Advanced, Recurrent or Metastatic Esophageal Squamous Cell Carcinoma

October 17, 2020 /Bio ValleyBIOON/ -- Bristol-Myers Squibb (BMS) recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion, recommending approval of a new indication for the anti-PD-1 therapy Opdivo (generic name: nivolumab). The new indication is for the treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) who have experienced disease progression following prior combination chemotherapy based on fluoropyrimidine and platinum.

The CHMP opinion represents the final step in the marketing authorization process prior to approval by the European Commission (EC). The CHMP’s opinion will now be submitted to the EC for review; the EC typically adopts the CHMP’s opinion and issues a final decision within two months. Opdivo was approved in Japan and the United States in February and June of this year, respectively. To date, it has been approved in five countries for the second-line treatment of patients with unresectable, advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC).

It is particularly worth mentioning that,Opdivo is the first approved for the aforementioned ESCS patient population, regardless of PD-L1 expression level.TumorImmunotherapy.Clinical data show that,Compared with chemotherapy, Opdivo significantly prolonged overall survival, and this benefit was independent of PD-L1 expression status.Patients with advanced esophageal squamous cell carcinoma (ESCC) have a poor prognosis and very limited treatment options. Opdivo will provide an important second-line treatment option for patients with ESCC, extending survival while improving quality of life.

The CHMP’s positive opinion is based on the results of the Phase III ATTRACTION-3 study (ONO-4538-24/CA209-473; NCT02569242). The data demonstrated that Opdivo yielded superior overall survival (OS) outcomes compared to taxane chemotherapy (investigator’s choice of docetaxel or paclitaxel) (HR=0.77; 95% CI: 0.62–0.96; p=0.0189). The median OS in the taxane chemotherapy group was 8.4 months (95% CI: 7.2–9.9), whereas the median OS in the Opdivo treatment group reached 10.9 months (95% CI: 9.2–13.3), regardless of PD-L1 expression levels.

Bristol-Myers Squibb GastrointestinalTumorIan M. Waxman, M.D., Head of Development, stated: “The CHMP’s positive opinion underscores the potential of Opdivo in the treatment of esophageal squamous cell carcinoma (ESCC) in the European Union. The ATTRACTION-3 trial demonstrated clinically meaningful survival benefits and a favorable safety profile. We look forward to the European Commission’s final decision, which could mark the first approval of immunotherapy for any upper gastrointestinal cancer in the EU. We remain committed to further exploring the potential benefits of Opdivo in the treatment of early-stage esophageal cancer.”

ATTRACTION-3 was a multicenter, randomized, open-label, global study that evaluated the efficacy and safety of Opdivo versus chemotherapy (docetaxel or paclitaxel) in patients with unresectable advanced or recurrent esophageal squamous cell carcinoma (ESCC) who were refractory to or intolerant of first-line fluoropyrimidine and platinum-based combination therapy. Patient enrollment occurred primarily in Asia, with up to 96% of patients in both treatment groups originating from Asia. In the study, patients received treatment until disease progression or unacceptable toxicity. The primary endpoint was overall survival (OS), and secondary endpoints included investigator-assessed overall response rate (ORR), progression-free survival (PFS), disease control rate (DCR), duration of response (DOR), and safety. The study was sponsored by Ono Pharmaceutical Co., Ltd. (Ono Pharma), Bristol-Myers Squibb’s partner for Opdivo.

The results showed that the study met its primary endpoint of overall survival (OS): compared with the chemotherapy group, the Opdivo treatment group demonstrated a statistically significant improvement in OS, with a 23% reduction in the risk of death (HR=0.77, 95% CI: 0.62-0.96, p=0.0189) and a median OS extension of 2.5 months (10.9 months [95% CI: 9.2-13.3] vs. 8.4 months [95% CI: 7.2-9.9]). The 12-month and 18-month survival rates (OS rates) were 47% (95% CI: 40-54) and 31% (95% CI: 24-37), respectively, in the Opdivo treatment group, compared to 34% (95% CI: 28-41) and 21% (95% CI: 15-27), respectively, in the chemotherapy group. Regardless ofTumorRegardless of PD-L1 expression levels, survival benefits with Opdivo were observed. Exploratory analyses of patient-reported outcomes demonstrated a significant overall improvement in quality of life for patients treated with Opdivo compared with chemotherapy.

Regarding the objective response rate (ORR), the Opdivo treatment group and the chemotherapy group were 19% (95% CI: 14-26) and 22% (95% CI: 15-29), respectively. However, the study showed that, compared with chemotherapy, Opdivo significantly prolonged the median duration of response (DOR: 6.9 months [95% CI: 5.4-11.1] vs. 3.9 months [95% CI: 2.8-4.2]). At the data cutoff, 7 patients in the Opdivo treatment group remained in response, compared with 2 in the chemotherapy group. There was no significant difference in progression-free survival (PFS) between the Opdivo treatment group and the chemotherapy group (HR=1.08 [95% CI: 0.87-1.34]).

In this study, the safety profile of Opdivo was consistent with that reported in previous studies in esophageal squamous cell carcinoma (ESCC) and other solid tumors. Compared with chemotherapy, Opdivo was associated with fewer treatment-related adverse events (TRAEs); the incidence of TRAEs of any grade was 60% in patients treated with Opdivo versus 95% in those receiving chemotherapy. The incidence of Grade 3 or 4 TRAEs was lower in the Opdivo group than in the chemotherapy group (18% vs. 63%), while the proportion of patients discontinuing treatment due to TRAEs was identical in both groups (9% each).

Esophageal cancer is the seventh most common cancer and the sixth leading cause of cancer-related death worldwide.DiagnosisThe five-year relative survival rate for patients with metastatic disease is 8% or lower. The two most common types of esophageal cancer are squamous cell carcinoma and adenocarcinoma, accounting for approximately 90% and 10% of all esophageal cancers, respectively.

Esophageal Cancer (Image Source: medindia.net)

It is estimated that 572,000 new cases are diagnosed annually, and approximately 500,000 people die from esophageal cancer. Most cases are diagnosed at an advanced stage, which affects patients’ daily lives, including their ability to eat. Asia has the highest prevalence of esophageal cancer, with 444,000 cases diagnosed each year, accounting for 80% of global esophageal cancer cases.

It is worth mentioning that in late July 2019, Merck & Co.’s PD-1 tumor immunotherapy Keytruda (brand name: Keytruda; generic name: pembrolizumab) was approved by the U.S. FDA for the treatment of patients with PD-L1-positive esophageal squamous cell carcinoma (ESCC), specifically: following oneFDAPatients with recurrent, locally advanced or metastatic ESCC who have progressed after one or more prior systemic therapies and whose tumors express PD-L1 (Combined Positive Score [CPS] ≥ 10) as determined by an approved test. Keytruda is the first approved treatment for recurrent, locally advanced or metastatic ESCC (TumorAnti-PD-1 therapy in patients expressing PD-L1 (CPS ≥ 10).

This approval is based on data from two clinical studies, KEYNOTE-181 (NCT02564263) and KEYNOTE-180 (NCT02559687). Data from the KEYNOTE-181 study demonstrated that in patients with esophageal squamous cell carcinoma (ESCC) expressing PD-L1 (CPS ≥10), those treated with Keytruda showed improved overall survival (OS) compared to those receiving chemotherapy (median OS: 10.3 months [95% CI: 7.0–13.5] vs. 6.7 months [95% CI: 4.8–8.6]; HR = 0.64 [95% CI: 0.46–0.90]). Data from the KEYNOTE-180 study showed that among 35 patientsTumorIn ESCC patients expressing PD-L1 (CPS ≥ 10), the ORR was 20% (95% CI: 8.0, 37.0). Among the 7 patients who achieved disease response, the DOR ranged from 4.2 months to 25.1+ months; 71% of patients (5 cases) had a DOR ≥ 6 months, and 57% of patients (3 cases) had a DOR ≥ 12 months. (Bioon.com)

Original Source: Bristol Myers Squibb Receives Positive CHMP Opinion Recommending Opdivo (nivolumab) as Second-Line Treatment for Unresectable Advanced, Recurrent or Metastatic Esophageal Squamous Cell Carcinoma