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PSM

PSM Abstract Session 1

10: Efficacy and safety of PD-L1 (atezolizumab) and VEGF (bevacizumab) inhibition in metastatic appendiceal adenocarcinoma

Saturday, February 17, 2024
10:35 AM - 10:45 AM AST
Location: Miramar I & II
Disclosure(s):
Michael G. White, MD, M.Sc.: No financial relationships to disclose
John Paul Shen, MD: BostonGene: Research Grant (Ongoing); Celsius Therapeutics: Research Grant (Terminated, January 2, 2024); Engine Biosciences: Advisor (Ongoing); NaDeNo Nanosciences: Advisor (Ongoing)
Introduction: AA remains an orphan disease, and recent studies have demonstrated that chemotherapy designed for colorectal cancer has limited benefit for many patients with AA. Clinical and preclinical evidence supporting the efficacy of combined VEGF and PD-1 inhibition in other tumor types provided a compelling rationale for investigating this combination in AA, where immune checkpoint inhibitors have unknown clinical benefit. We conducted a prospective, single arm phase 2 study evaluating efficacy and safety of atezolizumab in conjunction with bevacizumab (Atezo+Bev) in peritoneal metastatic AA.


Methods: Patients aged ≥ 18 years with AA not considered candidates for curative surgery, ECOG PS 0 – 2 were enrolled prospectively and treated with atezolizumab (840mg) and bevacizumab (15mg/kq) IV on a 21-day cycle.  The primary endpoint was objective response rate (ORR) per RECIST V1.1. Key pre-specified secondary endpoints were safety, disease control rate (DCR), progression-free (PFS) and overall (OS) survival.


Results: Between 4/2017 and 7/2020, 16 patients were enrolled. The ORR per RECISTv1.1 was 6.25% [1/16] (1 partial response). Disease control rate (DCR) was 100% with all 16 patients obtaining at least stable disease. Median PFS was 18.3 months (95% CI 8.93 – 29.5); median OS was not-yet-reached, lower bound of 95% CI > 29.5 months, with a median of 60 months of follow up. A machine-learning approach was used to select a synthetic cohort of 16 patients treated with standard-of-care (SOC) chemotherapy matched to trial patients’ tumor grade, molecular profile and line of therapy from a historical database of 3713 patients with AA. Atezo+Bev significantly improved PFS (18.3 vs. 4.6 mo, HR = 1.9, p = .041) relative to SOC control. Additionally, internally comparing Atezo+Bev to prior lines of SOC chemotherapy for the trial cohort also demonstrated superiority for Atezo+Bev (PFS 18.3 vs. 3 mo, HR = 3.4, p = < .0005). The longer PFS seen with Atezo+Bev compared to prior lines of SOC was consistent irrespective of tumor grade (8 well, 7 moderate, and 1 poorly differentiated tumor, Figure). Grade 3 adverse events occurred in 6 (37.5%) patients with no grade 4/5 events and no treatment discontinuation due to side-effects.


Conclusions: Atezo+Bev demonstrated higher-than-expected PFS and OS and decreased toxicity compared to SOC treatment. In light of recent prospective, randomized, studies demonstrating no benefit to 5-FU-based chemotherapy in low-grade AA, these data suggest Atezo-Bev be considered as a treatment option in this orphan disease. Further prospective studies are warranted.

Learning Objectives:

  • recognize a new active treatment in appendiceal adenocarcinoma, currently an orphan disease.
  • consider new treatment options for patients with appendiceal cancer who are not candidate for cytoreductive surgery
  • describe why appendiceal cancer is different that colorectal cancer