ASCO GICS 2015. Abstract 3: KEYNOTE-012.

ASCO Gastrointestinal Cancers Symposium 2015

ASCO GICS 2015. Abstract 3. Relationship between PD-L1 Expression and clinical outcomes in patients (pts) with advanced gastric cancer treated with the anti-PD-1 monoclonal antibody pembrolizumab (Pembro; MK-3475) in KEYNOTE-012.

Presenter: Kei Muro

Background: Tumors use the PD-1 pathway to evade immune surveillance. Pembrolizumab, an anti-PD-1 monoclonal antibody, has shown antitumor activity in advanced cancers. We assessed the safety and efficacy of pembrolizumab in patients with advanced gastric cancer in KEYNOTE-012 ( identifier NCT01848834).

Results: Of the 162 patients screened, 65 (40%) were PD-L1+. Of these 65 patients, 39 enrolled (19 from AP, 20 from ROW; median age 63 years [range 33-78]). The number of prior therapies for advanced disease ranged from 0 to 5; 67% received ≥2 prior therapies. Median follow-up duration was 8.8 months (range 6.2-12.6); 13 patients (33%) remain on therapy. Four patients experienced 5 total grade 3-5 drug-related adverse events: peripheral sensory neuropathy, fatigue, decreased appetite, hypoxia, and pneumonitis (n= 1 each). There was 1 drug-related death (hypoxia). ORR was 22% (95% CI 10-39) by central review and 33% (95% CI 19-50) by investigator review. Median time to response was 8 weeks (range 7-16), with a median response duration of 24 weeks (range 8+ to 33+). PD-L1 expression level was associated with ORR (1-sided P= 0.10). The 6-month PFS rate was 24%. The 6-month OS rate was 69%.

Conclusion: Pembrolizumab demonstrated manageable toxicity and promising antitumor activity in advanced gastric cancer. These results support the ongoing development of pembrolizumab for gastric cancer.


CARE Faculty Canadian Perspective:

Immuno-oncology is the subject of intensive investigation. PD-1 is a negative co-stimulatory receptor expressed on activated T cells.  PD-1 checkpoint inhibition results in sustained activation of effector T-cell function. In the KEYNOTE-012 phase I trial, the use of pembrolizumab, a humanized anti-PD1 mAB, in 39 patients with PD-L1 positive pretreated gastric adenocarcinoma demonstrated encouraging results with a 6 month OS rate of 69% and a durable ORR of 22% with acceptable safety, PD-L1 positivity was present in 40% of screened pts.  A phase 2 study is ongoing.

The CARE Oncology Faculty conducted a needs assessment with the aim of providing insights on the level of knowledge Canadian specialists have with regards to immuno-oncology.  The analysis revealed a limited understanding of immuno-oncology and that further education is required. It also identified concerns with cost, access and side effect management of I-O agents. Given the emerging evidence across multiple tumour types, it is increasingly important for oncologists to understand this new therapeutic arena.

- CARE Oncology Cancer Faculty

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