Assessment of Clinical Response Following Atezolizumab and Bevacizumab Treatment in Patients With Neuroendocrine Tumors: A Nonrandomized Clinical Trial

Background

Well differentiated NETs have been described as an “immunological desert” in recent years mainly due to the poor response rate data coming out of clinical trials of immunotherapy drugs. Poorly differentiated NEC has favoured better but mainly in the more obscure types. Which is why these data of a combo treatment containing one immunotherapy drug caught my eye.

What is atezolizumab? It is a type of monoclonal antibody and a type of immune checkpoint inhibitor. It’s a Programmed cell death protein -1 (PD-1)/ Ligand 1 (PD-L1) inhibitor. A drug that binds to the protein PD-L1 to help immune cells kill cancer cells better and is used to treat many different types of cancer, including cancers that express PD-L1. Atezolizumab is used alone or with other drugs to treat certain types of melanoma, hepatocellular carcinoma (a type of liver cancer), non-small cell lung cancer, small cell lung cancer, and urothelial cancer (a type of cancer in the bladder or urinary tract). It is also being studied in the treatment of other types of cancer. Atezolizumab may block PD-L1 and help the immune system kill cancer cells. Also called Tecentriq.

What is bevacizumab? It’s a vascular endothelial growth factor (VEGF) inhibitor. A drug that binds to the protein VEGF to help keep new blood vessels from forming and is used to treat many different types of cancer. Bevacizumab is used under the brand names Alymsys, Mvasi, Avastin, and Zirabev, alone or with other drugs, to treat certain types of cervical cancer, colorectal cancer, non-small cell lung cancer, renal cell carcinoma (a type of kidney cancer), and glioblastoma (a type of brain cancer). The Alymsys and Avastin brands of bevacizumab are also used to treat certain types of ovarian epithelial, fallopian tube, and primary peritoneal cancer. The Avastin brand is also used to treat certain types of hepatocellular carcinoma (a type of liver cancer). Bevacizumab is also being studied in the treatment of other types of cancer. It may prevent the growth of new blood vessels that tumors need to grow. Bevacizumab is a type of anti-angiogenesis agent (prevention of the growth of new blood vessels) and a type of monoclonal antibody (a type of protein that is made in the laboratory and can bind to certain targets in the body, such as antigens on the surface of cancer cells).

The Clinical Trial

The output from this Phase 2 clinical trial is below in the abstract published online (also see citation below). It should be noted this was a nonrandomised clinical trial where in certain situations is impossible or difficult to assign subjects to treatment by chance. Unlike randomized control studies, nonrandomized trials are vulnerable to bias because of the inability to control the balance of prognostic factors between the treatment groups.

Abstract

Importance: Therapies for patients with advanced well-differentiated neuroendocrine tumors (NETs) have expanded but remain inadequate, with patients dying of disease despite recent advances in NET therapy. While patients with other cancers have seen long-term disease control and tumor regression with the application of immunotherapies, initial prospective studies of single agent programmed cell death 1 inhibitors in NET have been disappointing.

Objective: To evaluate the response rate following treatment with the combination of the vascular endothelial growth factor inhibitor bevacizumab with the programmed cell death 1 ligand 1 inhibitor atezolizumab in patients with advanced NETs.

Design, setting, and participants: This single-arm, open-label nonrandomized clinical study in patients with rare cancers included 40 patients with advanced, progressive grade 1 to 2 NETs (20 with pancreatic NETs [pNETs] and 20 with *extrapancreatic NETs [epNETs]) treated at a tertiary care referral cancer center between March 31, 2017, and February 19, 2019. Data were analyzed from June to September 2021.

(*anywhere outside the pancreas)

Interventions: Patients received intravenous bevacizumab and atezolizumab at standard doses every 3 weeks until progression, death, or withdrawal.

Main outcomes and measures: The primary end point was objective radiographic response using Response Evaluation Criteria in Solid Tumors, version 1.1, with progression-free survival (PFS) as a key secondary end point.

Results: Following treatment of the 40 study patients with bevacizumab and atezolizumab, objective response was observed in 4 patients with pNETs (20%; 95% CI, 5.7%-43.7%) and 3 patients with epNETs (15%; 95% CI, 3.2%-37.9%). The PFS was 14.9 (95% CI, 4.4-32.0) months and 14.2 (95% CI, 10.2-19.6) months in these cohorts, respectively.

Conclusions and relevance: In this nonrandomized clinical trial, findings suggest that clinical responses in patients with NET may follow treatment with the combination of bevacizumab and atezolizumab, with a PFS consistent with effective therapies.

Trial registration: ClinicalTrials.gov Identifier: NCT03074513.

Full details can be found in:

Halperin DM, Liu S, Dasari A, Fogelman D, Bhosale P, Mahvash A, Estrella JS, Rubin L, Morani AC, Knafl M, Overeem TA, Fu SC, Solis LM, Parra Cuentas E, Verma A, Chen HL, Gite S, Subashchandrabose P, Dervin S, Schulze K, Darbonne WC, Yun C, Wistuba II, Futreal PA, Woodman SE, Yao JC. Assessment of Clinical Response Following Atezolizumab and Bevacizumab Treatment in Patients With Neuroendocrine Tumors: A Nonrandomized Clinical Trial. JAMA Oncol. 2022 Jun 1;8(6):904-909. doi: 10.1001/jamaoncol.2022.0212. PMID: 35389428; PMCID: PMC8990358. Note this is a subscription article but the abstract should be sufficient for most.

Next steps

It is not yet known if this will progress to Phase 3. However, I have setup an alert so that I can bring you news of any developments.

Disclaimer

I am not a doctor or any form of medical professional, practitioner or counsellor. None of the information on my website, or linked to my website(s), or conveyed by me on any social media or presentation, should be interpreted as medical advice given or advised by me.

Neither should any post or comment made by a follower or member of my private group be assumed to be medical advice, even if that person is a healthcare professional.

Please also note that mention of a clinical service, trial/study or therapy does not constitute an endorsement of that service, trial/study or therapy by Ronny Allan, the information is provided for education and awareness purposes and/or related to Ronny Allan’s own patient experience. This element of the disclaimer includes any complementary medicine, non-prescription over the counter drugs and supplements such as vitamins and minerals.

General Clinical Trials Disclaimer

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided in the clinical trials document. It’s very important to check the trial inclusion and exclusion criteria before making any contact. If you need questions, the articles here is very useful Questions to Ask About Clinical Trials | Cancer.Net

The inclusion of any trial within this blog should not be taken as a recommendation by Ronny Allan.

Finally

Whenever I post about a trial or study, some people get excited without understanding that these new treatments and capabilities can very often take years to come to fruition and it’s also possible that clinical trials can be halted, or that national approval agencies will not approve the final product. Plus, not everyone will be eligible, so always check the exclusion and inclusion criteria in the relevant clinical trials document. Please bear that in mind when reading studies/clinical trials posted on RonnyAllan.NET