Neoadjuvant or concurrent atezolizumab with chemoradiation for locally advanced cervical cancer: a randomized phase I trial
Combined immune checkpoint blockade (ICB) and chemoradiation (CRT) is approved in patients with locally advanced cervical cancer (LACC) but optimal sequencing of CRT and ICB is unknown. NRG-GY017 (NCT03738228) was a randomized phase I trial of atezolizumab (anti-PD-L1) neoadjuvant and concurrent with CRT (Arm A) vs. concurrent with CRT (Arm B) in patients with high-risk node-positive LACC. The primary endpoint was the fraction of expanded tumor-associated T-cell receptor (TCR) clones in blood at day 21 as a surrogate measure of anti-tumor immune response. Secondary objectives were safety and feasibility, 2-year disease-free survival (DFS), and predictive value of PD-L1 expression. Forty patients were randomized, 36 received treatment, and 25 were evaluable for the primary endpoint. After cycle 1, there was peripheral expansion of higher proportion of tumor-associated TCR clones in Arm A than in Arm B (p = 0.0025) that remained higher at day 21, meeting the pre-specified endpoint on two-sample T-test (p = 0.052), but not on sensitivity analysis by Wilcoxon test (p = 0.13). At the median follow up of 25.8 months, 2-year DFS was 76% in Arm A and 56% in Arm B (p = 0.28). There were no new safety signals. In conclusion, neoadjuvant ICB prior to CRT was safe and was associated with immunologically and clinically favorable outcomes, warranting larger confirmatory studies.
Authors
- C.L. Ferguson (ORCID: https://orcid.org/0000-0002-5949-6333)
- Cara Mathews (ORCID: https://orcid.org/0000-0001-8461-4568)
- Charles A. Leath (ORCID: https://orcid.org/0000-0002-4034-6845)
- Barbara L. Banbury (ORCID: https://orcid.org/0000-0001-7332-7117)
- Ned Sherry
- Laura L. Holman (ORCID: https://orcid.org/0000-0003-1580-5381)
- David M. O’Malley (ORCID: https://orcid.org/0000-0002-2828-0177)
- Elad Sharon (ORCID: https://orcid.org/0000-0002-0044-9719)
- Dmitriy Zamarin (ORCID: https://orcid.org/0000-0002-0094-0161)
- Wei Deng (ORCID: https://orcid.org/0000-0003-1778-2013)
- Heather A. Lankes (ORCID: https://orcid.org/0000-0001-8814-5033)
- Giulio Pesci
- Loren K. Mell
- Junzo Chino (ORCID: https://orcid.org/0000-0002-3633-9685)
- Sharad Ghamande (ORCID: https://orcid.org/0000-0003-2242-2215)
- Jyoti Mayadev (ORCID: https://orcid.org/0000-0003-4786-8192)
- Roisin E. O’Cearbhaill (ORCID: https://orcid.org/0000-0001-8217-4554)
- Carol Aghajanian (ORCID: https://orcid.org/0000-0003-0851-3225)
- Larry J. Copeland (ORCID: https://orcid.org/0000-0001-6204-0962)
- Robert S. Mannel
- Russell J. Schilder
- Hayeon Kim (ORCID: https://orcid.org/0000-0002-8869-3176)
- Elizabeth Hopp (ORCID: https://orcid.org/0000-0002-0577-0501)
- Alexander Olawaiye
Institutions
- Memorial Sloan Kettering Cancer Center (US)
- Duke University (US)
- Providence College (US)
- Medical College of Wisconsin (US)
- Augusta University (US)
- UC San Diego Health System (US)
- The Ohio State University Wexner Medical Center (US)
- University of Alabama at Birmingham (US)
- University of California San Diego (US)
- Adaptive Biotechnologies (United States) (US)
- Dana-Farber Cancer Institute (US)
- UPMC Hillman Cancer Center (US)
- Women & Infants Hospital of Rhode Island (US)
- University of Pittsburgh Medical Center (US)
- NRG Oncology (US)
- University of Oklahoma Health Sciences Center (US)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-01-09
- DOI
- https://doi.org/10.1038/s41467-024-55200-2
- Citations
- 13
- Primary Topic
- Endometrial and Cervical Cancer Treatments
- Type
- article
- Field-Weighted Citation Impact
- 26.74
Funders
- Ohio State University
- University of Oklahoma
- NRG Oncology
- Moores Cancer Center, UC San Diego Health
- National Institutes of Health
- Genentech
- University of California, San Diego
- University of Oklahoma Health Sciences Center
- National Cancer Institute