Nivolumab monotherapy shows promise in treating gastric, GE junction cancers

SAN FRANCISCO — Nivolumab monotherapy was well tolerated and showed antitumor activity in patients with advanced and metastatic gastric or gastroesophageal junction cancers who received heavy pretreatment, according to initial results from the CheckMate-032 trial presented at the Gastrointestinal Cancers Symposium.

Perspective from David P. Ryan, MD, MD

“Nivolumab is a fully human anti-program death-1 immunoglobulin G4 monoclonal antibody with a favorable safety profile and demonstrated efficacy in multiple tumor types,” Dung T. Le, MD, from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, said during her presentation. “The phase 1/2 randomized, open-label CheckMate-032 trial is a multitumor cohort study including patients with lung, breast, bladder, pancreatic and ovarian cancer who received nivolumab monotherapy or in combination with ipilimumab. The results presented today are the preliminary results for patients with locoregionally advanced or metastatic gastric or [gastroesophageal] junction cancer who received nivolumab monotherapy.”

Dung T. Le

Fifty-nine patients from the U.S. and European Union received nivolumab monotherapy (Opdivo, Bristol-Myers Squibb; 3 mg/kg IV every 2 weeks) until disease progression or intolerable toxicity. PD-L1 positivity was not mandated for inclusion. A median of five doses were administered (range, 1-31).

Overall, 76% of patients were men, median age was 60 years (range, 29-80 years), 83% had been treated with at least two prior regimens, 15% had esophageal cancer, 53% gastroesophageal (GE) junction cancer and 31% gastric cancer.

Objective response rate served as the primary endpoint, while adverse events, overall survival, OS rate, progression-free survival, progression-free survival rate and duration of response served as secondary endpoints.

At the end of the study period (median follow-up, 4.6 months), 7% of patients remained on active treatment, while 78% patients discontinued treatment due to disease progression, 5% due to drug toxicity and 10% for other reasons.

Overall response rate was 14% — with one patient achieving a complete response and seven achieving a partial response — and 11 of the patients had stable disease, with a disease control rate of 32%.

Median time to response was 1.6 months, and median duration of response was 7.1 months (95% CI, 0.0+, 13.2). Median OS was 5 months, 6-month OS rate was 49% and 1-year OS rate was 36%.

Overall, 39% of tumor samples were PD-L1 positive (1% expression cutoff). The OS rate was 27% among patients with PD-L1 positive tumors compared with 12% among patients with PD-L1 negative tumors.

“Treatment-related [adverse events] were similar to prior nivolumab monotherapy studies,” Le said. No grade five or treatment-related adverse event or serious adverse event deaths occurred. Treatment-related adverse events occurred in 69% of patients, most of which were fatigue. Seventeen percent of patients had a grade 3/4 treatment-related adverse event, while 10% of patients had a treatment-related serious adverse event.

“In conclusion, nivolumab monotherapy was well tolerated in patients with metastatic gastric, esophageal or GE junction cancers,” Le said. “The [adverse event] profile was similar to those seen in patients with other tumor types. Confirmed response was 14% in heavily pretreated patients in a patient population that consisted of both PD-L1 positive and PD-L1 negative patients; 49% and 36% of chemotherapy refractory patients were still alive at 6 and 12 months, respectively.” – by Adam Leitenberger

Reference:

Le D, et al. Abstract 06. Presented at: Gastrointestinal Cancers Symposium; Jan. 21-23, 2016; San Francisco.

Disclosure: Le reports she has received research funding from Aduro Biotech, Bristol-Myers Squibb and Merck. Please see the abstract for a full list of all other researchers’ relevant financial disclosures.

Perspective

David P. Ryan, MD, MD

The CheckMate-032 and KEYNOTE-028 trials study single-agent, anti-PD1 antibodies against patients with refractory metastatic adenocarcinoma of the stomach or the gastroesophageal junction and esophagus.

The major take-home point is that this class of drug is active against these types of cancers. Where the response rate is going to sort out after several hundred patients get treated is yet to be seen, but we think that it's reasonable to assume that there's a response rate in the 10% to 20% range, at least. That means that these are really worthwhile drugs to study and hopefully go on to registration in this setting.

The main take-home points are that:

A. Not everybody is responding.

B. We don't know why some people are responding and some people aren't responding. PD-L1 expression doesn't seem to be a robust biomarker in these patients and further research is necessary to figure out who is responding and who isn't responding.

C. We need long-term follow-up to see if the data is going to be anything like melanoma, where there's a subset of patients who respond for many, many weeks.

There are some phase 3 studies underway in this setting and we very much look forward to those results.

David P. Ryan, MD, MD

Chief of Hematology/Oncology, Medical Oncologist

Massachusetts General Hospital

Associate Professor of Medicine

Harvard Medical School

Disclosures: Ryan reports honoraria from UpToDate, consulting or advisory roles for Medimmune, and patents, royalties and other intellectual property from McGraw Hill Chapter Royalties.