The following article features coverage from the ASCO Gastrointestinal Cancers Symposium 2021 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Frontline pembrolizumab, trastuzumab, and chemotherapy demonstrated “promising efficacy” in HER2-positive advanced gastric and gastroesophageal junction (GEJ) cancer irrespective of PD-L1 status, according to updated clinical and molecular profiling data from the phase 1b/2 PANTHERA trial presented at the 2021 Gastrointestinal Cancers Symposium.

At a median follow-up of 18.2 months, PANTHERA’s primary end point analysis showed that the overall response rate among the 43 patients who received the triplet therapy was 76.7% (95% CI, 61.4-88.2). More than half of patients (56.6%) had a reduction in tumor burden greater than 50%. The disease control rate was 97.7% (95% CI, 87.7-99.9).

Clinical features including PD-L1 status and metastatic organ or baseline tumor burden “were not related to survival,” Sun Young Rha, MD, PhD, of Yonsei Cancer Center in Seoul, South Korea, said during the presentation. Combined positive score (CPS) analysis at indicated that 39.5% of patients had a CPS of less than 1%, 48.8% had a CPS of 1% or more, 11.6% had a CPS of 10% or greater, and 11.6% were not evaluated for CPS at diagnosis.

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PANTHERA’s secondary end points included progression-free survival (PFS), overall survival (OS), duration of response, safety, and predictive biomarker analysis by targeted next-generation sequencing. The median PFS was 8.6 months (7.2-16.4), and the median OS, 19.3 months (95% CI, 16.5-not reached).

Biomarker analyses betrayed varying survival benefits. For example, patients with HER2 amplification per next-generation sequencing (≥ 4 copy number) were associated with a statistically significant survival benefit vs those without HER2 amplification (median PFS, 22.0 months vs 7.7 months; P =.0275). This trend extended to patients with RTK/RAS pathway alterations compared with those with wild-type RTK/RAS (median PFS, 13.8 months vs 4.9 months; P = .001).

Though the correlative biomarkers derived from the PANTHERA trial “need to be validated through ongoing trials,” according to Rha, the first-line regimen demonstrated anticancer activity and may therefore be a viable strategy for the treatment of HER2-positive advanced gastric and GEJ cancer. The biomarkers identified in PANTHERA will be validated in the phase 3 KEYNOTE-118 study ( identifier: NCT03615326), which is testing pembrolizumab plus trastuzumab in combination with standard-of-care chemotherapy vs trastuzumab and chemotherapy in individuals with advanced HER2-positive gastric or GEJ cancer.

Disclosures: Some of the study authors disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study.

Read more of Cancer Therapy Advisor‘s coverage of the ASCO GI 2021 meeting by visiting the conference page.


Rha SY, Lee C-K, Kim HS, et al. A multi-institutional phase Ib/II trial of first-line triplet regimen ([embrolizumab, trastuzumab, chemotherapy) for HER2-positive advanced gastric and gastroesophageal junction cancer (PANTHERA trial): molecular profiling and clinical update. Presented at: 2021 Gastrointestinal Cancers Symposium; January 15-17, 2021. Abstract 218.