403MO - Atezolizumab in combination with bevacizumab for patients with unresectable/metastatic anal cancer

Background

Immune checkpoint blockade agents targeting PD-1/PD-L1 as monotherapy are associated with responses in 10-25% of patients (pts) with metastatic human papillomavirus (HPV)-associated malignancies. VEGF signaling has been linked with immune evasion and suppression within the tumor microenvironment as a possible resistance mechanism to immunotherapy. The combination of the anti-PD-L1 antibody atezolizumab (A) and anti-VEGF antibody bevacizumab (B) demonstrated survival benefit in virally linked hepatocellular carcinoma. Here we evaluated the combination of A and B for pts with unresectable HPV-associated cancers.

Methods

Pts with previously treated, immunotherapy-naïve HPV-associated cancers were eligible for this single-arm phase II study. Pts received A (1200 mg) and B (15 mg/kg) intravenously every 3 weeks until development of progressive disease or drug intolerance. Responses were evaluated every 9 weeks by RECIST Criteria v1.1. The primary objective was to measure best overall response rate (ORR). Pretreatment and on-treatment biopsies were collected for biomarker analyses.

Results

20 pts with unresectable squamous cell carcinoma of the anal canal were treated with A+B (median number of doses, 6). Median age was 59 years (range, 43-80). 60% of pts had received only 1 prior line of therapy. Partial responses, both verified, were seen in 2 pts (ORR 10%, 95% confidence interval (CI): 1.2-32), with stable disease in 11 (55%) pts. Median progression-free survival (PFS) was 4.1 months (95% CI: 2.6-NA). 12-month PFS rate was 20% (95% CI: 8-52). Median overall survival (OS) was 11.6 months (95% CI, 9.5-20). Grade ≥3 adverse events (AE) were observed in 7 (35%) pts, with one grade 5 treatment-related AE (bowel perforation). The most common grade ≥3 AEs were hyponatremia (N=4), infection (N=2), and hypertension (N=2). Updated biomarker analyses will be presented.

Conclusions

A + B displays potential clinical benefit for pts with treatment-refractory metastatic anal cancer. Further investigation to immunotherapy combination trials is warranted to build upon outcomes with immune checkpoint monotherapies. Ongoing correlative studies may identify predictive biomarkers associated with benefit for this combination.

Clinical trial identification

NCT03074513.

Editorial acknowledgement

Legal entity responsible for the study

The University of Texas M.D. Anderson Cancer Center.

Funding

Genentech.

Disclosure

V. Morris: Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): EMD Serono; Research grant/Funding (institution): Immatics; Advisory/Consultancy: Array Biopharma; Advisory/Consultancy, Data safety monitoring board: Incyte. I.I. Wistuba: Honoraria (self), Research grant/Funding (self): Genentech; Honoraria (self), Research grant/Funding (self): Bayer; Honoraria (self), Research grant/Funding (self): AstraZeneca/Medimmune; Honoraria (self), Research grant/Funding (self): Pfizer; Honoraria (self), Research grant/Funding (self): HTG Molecular; Honoraria (self): Asuragen; Honoraria (self), Research grant/Funding (self): Merck; Honoraria (self): GlaxoSmithKline; Honoraria (self): GuardantHealth; Honoraria (self): Oncocyte; Honoraria (self): MSD; Research grant/Funding (self): Oncoplex; Research grant/Funding (self): DepArray; Research grant/Funding (self): Bristol-Myers Squibb; Research grant/Funding (self): Adaptive; Research grant/Funding (self): Adaptimmune; Research grant/Funding (self): EMD Serono; Research grant/Funding (self): Takeda; Research grant/Funding (self): Amgen; Research grant/Funding (self): Karus; Research grant/Funding (self): Johnson & Johnson; Research grant/Funding (self): Iovance; Research grant/Funding (self): 4D; Research grant/Funding (self): Novartis; Research grant/Funding (self): Akoya. P. Hwu: Research grant/Funding (institution): GlaxoSmithKline; Officer/Board of Directors: Immatics; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Dragonfly. J.C. Yao: Research grant/Funding (self): Ipsen; Research grant/Funding (self): Chiasma; Research grant/Funding (self): Hutchinson Medi Pharma; Research grant/Funding (self): Advanced Accelerator Applications; Research grant/Funding (self): Novartis; Research grant/Funding (self): Tarveda; Research grant/Funding (self): Crinetics. D. Halperin: Research grant/Funding (institution): Genentech; Research grant/Funding (self): Tarveda; Advisory/Consultancy, Research grant/Funding (self): Advanced Accelerator Applications; Advisory/Consultancy, Research grant/Funding (self): Lexicon; Research grant/Funding (self): Incyte; Research grant/Funding (self): ThermoFisher; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Curium. All other authors have declared no conflicts of interest.