Neoadjuvant atezolizumab plus docetaxel/oxaliplatin/capecitabine in non-metastatic gastric and gastroesophageal junction adenocarcinoma: The PANDA trial.

Abstract

4059 Background: Immune checkpoint blockade improves clinical outcomes for patients with gastric and gastro-esophageal junction (GEJ) cancers, but its efficacy and impact on the tumor microenvironment in non-metastatic, resectable disease remains largely unknown. Peri-operative FLOT, the current standard-of-care, leads to pathologic complete responses (pCR) and major pathologic responses (MPR) in 16% and 37% of patients, respectively. An important open question is whether PDL-1 blockade monotherapy can prime the tumor microenvironment in a favorable manner, prior to combination with chemotherapy. Methods: We report results from the phase 2 PANDA trial (NCT03448835) of neoadjuvant atezolizumab (anti-PDL-1) plus docetaxel, oxaliplatin, and capecitabine (DOC) in patients with resectable gastric or GEJ adenocarcinoma. Patients received a single cycle of atezolizumab monotherapy, followed by 4 cycles of atezolizumab+DOC. Tumor tissue was collected at baseline, after atezolizumab monotherapy, the first atezolizumab+DOC, and at resection. The primary endpoints were safety and feasibility in 20 patients, and secondary endpoints included MPR (<10% viable tumor rest) and disease-free survival. Results: Twenty patients, of which 18 with mismatch repair (MMR) proficient and two with MMR-deficient tumors, were evaluable for safety and efficacy analyses. MPR was observed in 14/20 patients (70%; 95% CI 46–88%), including 9 pCR (45%; 95% CI 23-68%). Among patients with intestinal type adenocarcinoma, 12/15 (80%; 95% CI 52-96%) had an MPR, with 9/15 (60%; 95% CI 32-84%) pCR. Treatment was well tolerated, with two patients (10%) experiencing a grade 3 immune adverse event. At a median follow-up of 29 months (IQR 16-34), 15 patients (75%) were alive and disease-free. None of the patients with an MPR recurred. All patients underwent resections without treatment-related delays and no unexpected surgical complications were documented. Translational analyses, including baseline PDL-1 CPS score and whole exome sequencing (WES), plus CD8 T-cell infiltration and RNA sequencing at 4 timepoints will be presented at the meeting. Conclusions: Our data show that the addition of atezolizumab to neoadjuvant chemotherapy leads to promising pathologic responses in gastric/GEJ adenocarcinoma, which appears to be higher than in historical controls, with no recurrences in responders. These data should be validated in a large randomized controlled trial. Clinical trial information: NCT03448835.

Evaluation of neoadjuvant immunotherapy in resectable gastric/gastroesophageal junction tumors: a meta-analysis and systematic review

“…Among the 33 included studies, there were seven randomized controlled trials (RCTs) ( 31 , 35 , 39 , 40 , 54 , 56 , 58 ) and 26 single-arm open-label cohort studies ( 27 , 28 , 30 , 32 – 34 , 36 – 38 , 41 – 53 , 55 , 57 , 59 , 60 ). The main neoadjuvant immunotherapy drugs used were avelumab, camrelizumab, pembrolizumab, sintilimab, tislelizumab, nivolumab, LP002, and durvalumab.…”

Synergistic Toxicities from Multiple Therapies for Synchronous Malignancies

“…Toxicity data from this trial will be insightful to evaluate if the phenomena we describe in our case report are common. Additionally, the PANDA trial [5] combines capecitabine, oxaliplatin, and docetaxel with atezolizumab in a neoadjuvant fashion for resectable gastric and gastro-esophageal junction cancers. We eagerly await the toxicity data from this study as well.…”

Application of immune checkpoint inhibitors for resectable gastric/gastroesophageal cancer

“…The median follow-up of 29 months revealed a DFS rate of 75%. Two patients (10%) experienced grade 3 immune-related adverse events (IRAEs) ( Verschoor et al, 2022 ). Another single-arm, phase 2 trial (NCT03488667), also reported at ASCO 2022, showed 19% ypCR (tumor regression score, TRS = 0) and 92% pathological response (TRS ≤2) in 26 of 35 patients treated with neoadjuvant mFOLFOX plus pembrolizumab, with grade 3/4 toxicities reported in 21 patients ( Sun et al, 2022 ).…”