Neoadjuvant atezolizumab plus chemotherapy in gastric and gastroesophageal junction adenocarcinoma - the phase 2 PANDA trial

Sep 21, 2026

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Gastric and gastroesophageal junction (G/GEJ) cancers have poor prognosis, and while immune checkpoint blockade is standard for metastatic disease, its effects in early nonmetastatic settings remain unclear. The phase 2 PANDA trial tested neoadjuvant atezolizumab followed by atezolizumab plus docetaxel, oxaliplatin and capecitabine in resectable tumors. Treatment was safe and feasible with no grade 4–5 immune-related events, enabling resection without delays. Major pathologic responses occurred in 70% and responders showed higher baseline PD-1+CD8+ T-cell infiltration, supporting further validation.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages32

Reading Time1 h 21 min

AccessFree to download

PANDA trial design and treatment course

Safety and feasibility endpoints

Pathologic response and survival outcomes

Tumor microenvironment and translational analyses

| nature medicine | | | | --- | --- | --- | | Article [https://doi.org/10.1038/s41591-023-02758-x](https://doi.org/10.1038/s41591-023-02758-x) | | | | Neoadjuvantatezolizumab plus chemotherapy in gastric and gastroesophagealjunction adenocarcinoma:
the phase 2 PANDA trial | | | | Received: 12 May 2023
Accepted: 7 December 2023
Published online: 8 January 2024 Check for updates | A list of authors and their affiliations appears atthe end of the paper
Gastric and gastroesophageal junction (G/GEJ) cancers carry a poor prognosis, and despite recent advancements, most patients die of their disease. Although immune checkpoint blockade became part of the standard-of-care for patients with metastatic G/GEJcancers, its efficacy and impact on the tumor microenvironment (TME) in early disease
remain largely unknown. We hypothesized higher efficacy of neoadjuvant immunotherapy plus chemotherapy inpatients with nonmetastatic G/GEJ cancer. In the phase 2 PANDA trial, patients with previously untreated resectable G/GEJ tumors (n = 21) received neoadjuvant treatment with one cycle of atezolizumab monotherapy followed by four cyclesofatezolizumab plus docetaxel, oxaliplatin and capecitabine. Treatment was well tolerated. There were grade 3 immune-related adverse eventsintwoof 20 patients (10%) but no grade 4 or 5 immune-related adverse events, and all patients underwent resection without treatment-related delays, meeting the primary endpoint of safety and feasibility. Tissue was obtained at multiple time points, allowing analysis of the effects of single-agent anti-programmed cell death ligand
1 (PD-L1) and the subsequent combination with chemotherapy ontheTME. Twenty of 21 patients underwent surgery and were evaluable for secondary pathologic response and survival endpoints, and 19 were evaluable for exploratory translational analyses. A major pathologic response (≤10% residual viable tumor) was observed in 14 of 20 (70%, 95% confidence interval 46–88%) patients, including 9 (45%, 95% confidence interval 23–68%) pathologic complete responses. Ata median follow-up of 47 months, 13 of 14 responders were alive and disease-free, and five of six nonrespondershad died asa result of recurrence. Notably, baseline anti-programmed cell death protein 1 (PD-1)+CD8+ T cell infiltration was significantly higher in responders versus nonresponders, and comparison ofTME alterations following anti-PD-L1 monotherapy versus the subsequent combination with chemotherapy showed an increased immune activation on single-agent PD-1/L1 axis blockade. On the basis of these data, monotherapy anti-PD-L1 before its combination with chemotherapy warrants further exploration and validation ina larger cohort of patients with nonmetastatic G/GEJ cancer. ClinicalTrials.gov registration: NCT03448835. | | [e-mail:](e-mail: m.chalabi@nki.nl)[ m.chalabi@nki.nl](e-mail: m.chalabi@nki.nl) G/GEJ cancers represent a principal cause of mortality, ranking asthe fourth most common cause of cancer-related death worldwide1. Despite improvement of survival through implementation of perioperative chemotherapy and chemoradiotherapy, overall prognosis remains poor, with a 5-year survival of patients with locally advanced G/GEJadenocarcinoma of less than 50%(refs.2,3). In the pivotal FLOT4 study, comparing FLOT chemotherapy (docetaxel, oxaliplatin, leucovorinand fluorouracil) with the then standard-of-care—epirubicin, cisplatin, fluorouracil/capecitabine—FLOT led to significant improvement in overall survival (OS, 35 versus 50 months) and disease-free survival (DFS, 30 versus 18 months)3,4. Moreover, higher rates of pathologic complete responses (pCR, 16%) and near-complete responses (21%) were observed in FLOT-treated patients compared to epirubicin, cisplatin, fluorouracil/capecitabine (6% and 17%, respectively) in the FLOT4-AIO study4. On the basis of these data, FLOT has become standard-of-care. Over the past decade, immune checkpoint blockade (ICB) has emerged

FAQs

What was the main safety focus of the phase 2 PANDA trial?

The trial evaluated safety and feasibility, with immune-related adverse events monitored and all patients proceeding to resection without treatment-related delays.

How effective was neoadjuvant atezolizumab-based therapy in achieving major pathologic response?

Among evaluable patients, major pathologic response (≤10% residual viable tumor) was observed in 14 of 20 (70%), including 9 pathologic complete responses.

What translational signals distinguished responders from nonresponders?

Baseline anti-PD-1+CD8+ T-cell infiltration was significantly higher in responders, and tumor microenvironment analyses suggested increased immune activation after combination therapy versus anti-PD-L1 monotherapy alone.

Sep 21, 2026

Upload by Patrick