Neoadjuvant Atezolizumab and Chemo Show Potential in Gastric/GEJ Cancer

3D Illustration of esophageal cancer in the human male: © Lars Neumann - stock.adobe.com

April is Esophageal Cancer Awareness Month. This month, Targeted Oncology is highlighting research in the field of esophageal cancer treatment.

The anti-PD-L1 agent atezolizumab (Tecentriq) given as a monotherapy before being combined with chemotherapy warrants further research in patients with nonmetastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma, according to findings from the phase 2 PANDA trial (NCT03448835).¹

Of 20 patients who underwent surgical resection following treatment with atezolizumab monotherapy followed by atezolizumab plus docetaxel, oxaliplatin, and capecitabine, 14 patients (70%; 95% CI, 46%-77%) experienced a major pathologic response (MPR) with 10% or less of residual viable tumor remaining. Nine patients (45%; 95% CI, 23%-68%) experienced pathologic complete responses (pCR). pCRs were observed among patients with stage I through IIIB tumors, highlighting the regimen’s efficacy, even in advanced disease.

Further, in patients who responded to treatment, baseline anti-PD-1-positive, CD8-positive T-cell infiltration was notably higher and increased immune activation on the single-agent PD-(L)1 axis blockade was observed within the tumor microenvironment.

“Importantly, pathologic response showed an excellent correlation with survival, with 13 of 14 responders without disease recurrence after a median follow-up of 47 months, whereas 5 of 6 nonresponders had a recurrence and died of their disease. Although previous studies in G/GEJ cancer have shown an association between response to neoadjuvant chemotherapy or chemoradiotherapy and outcome our data indicate that the association may be stronger and more similar to patients receiving neoadjuvant immunotherapy for [non-small cell lung cancer], melanoma, colon and bladder cancer, where patients with MPR and pCR have a negligible risk of disease recurrence,” study authors wrote.

At a follow-up of 47 months (range, 11-59), 93% of patients (n = 13) who had a pCR or MPR were alive and disease free, highlighting the strong correlation between response and clinical outcomes. The median disease-free survival (DFS) was not reached (95% CI, 38-not reached), and the median DFS at 3 years was 73% (95% CI, 55%-97%). Among nonresponders, disease recurrence happened at a median of 10 months following surgery (range, 5-29).

A total of 21 patients were enrolled in the phase 2 study. Patients had a median age of 62 (range, 46-76), and 90% (n = 19) of patients were male. Three patients had mismatch repair deficient (dMMR) tumors. Two of these patients underwent surgery, and both experienced a pCR.

Regarding safety, the study met its primary end point of safety and feasibility. Eleven of 20 patients (55%) experienced immune-related adverse events (irAEs); 3 grade 3 irAEs of hepatitis, headache, and diarrhea were reported in 2 patients (10%). No grade 4 or 5 irAEs were reported. There were no treatment-related delays for patients who underwent surgery. Moreover, there were no unexpected surgical complications and no intraoperative complications or surgery-related deaths.

REFERENCE:

1. Verschoor YL, van de Haar J, van den Berg JG, et al. Neoadjuvant atezolizumab plus chemotherapy in gastric and gastroesophageal junction adenocarcinoma: the phase 2 PANDA trial. Nat Med. 2024;30(2):519-530. doi:10.1038/s41591-023-02758-x