Advances in Cervical Cancer: Prevention, Immunotherapy, and the Rise of Antibody-Drug Conjugates: With Ursula A. Matulonis, MD; and Meghan E. Shea, MD

From Discovery to Delivery: Charting Progress in Gynecologic Oncology, hosted by Ursula A. Matulonis, MD, brings expert insights into the most recent breakthroughs, evolving standards, and emerging therapies across gynecologic cancers. Dr Matulonis is chief of the Division of Gynecologic Oncology and the Brock-Wilson Family Chair at the Dana-Farber Cancer Institute, as well as a professor of medicine at Harvard Medical School, both in Boston, Massachusetts.

In this episode, Dr Matulonis was joined by Meghan E. Shea, MD, an attending medical oncologist and ambulatory medical director and disease program leader for medical oncology at Beth Israel Deaconess Medical Center in Boston. Together, they explored the current landscape of cervical cancer, from the urgent need for expanded vaccination and screening to the evolving role of immunotherapy and antibody-drug conjugates (ADCs) across disease settings.

Dr Shea opened by addressing the epidemiology of cervical cancer, noting that despite decades of progress, rates are now plateauing and rising among women under 50 years of age. She identified 3 interrelated drivers of this trend: declining rates of routine gynecologic screening, inconsistent uptake of human papillomavirus (HPV) vaccination, and persistent high-risk HPV infections, particularly HPV 16 and 18, which are responsible for most cases.

The conversation then turned to the effect of immunotherapy on cervical cancer treatment. Dr Shea traced the evolution of pembrolizumab (Keytruda) from its initial 2018 approval as a single agent in recurrent/metastatic disease to its more recent integration into the frontline setting. The phase 3 KEYNOTE-A18 trial (NCT04221945) demonstrated that adding pembrolizumab to standard weekly cisplatin-based chemoradiation significantly improved outcomes for patients with locally advanced disease. Although responses to immunotherapy, when they occur, are often durable, Dr Shea acknowledged that response rates remain lower than anticipated for a virally driven malignancy, underscoring the need for novel combinations and a deeper understanding of resistance mechanisms. Drs Matulonis and Shea both agreed that immunotherapy combined with ADCs represents one of the most compelling directions for the field, with phase 2 data for sacituzumab tirumotecan plus pembrolizumab generating interest ahead of anticipated phase 3 results.

On the ADC front, Dr Shea reviewed the 2 agents in this class that are currently FDA-approved for cervical cancer. Tisotumab vedotin-tftv (Tivdak) offers the advantage of biomarker-independent use, though its requirement for ophthalmologic monitoring at every treatment visit creates real-world access challenges outside major academic centers. Trastuzumab deruxtecan-nxki (Enhertu), approved in the HER2 immunohistochemistry 3+ setting based in part on the results of the phase 2 DESTINY-PanTumor02 trial (NCT04482309), has generated robust response rates but is most likely to benefit patients with adenocarcinoma. Dr Shea also highlighted additional targets under investigation, including Trop-2, Nectin-4, and B7-H4, with multiple phase 3 trials ongoing in both the frontline and recurrent settings.

The discussion closed with a look at the locally advanced disease landscape, where the NRG Oncology cooperative group is conducting a phase 3 trial to evaluate whether integrating the neoadjuvant carboplatin/paclitaxel regimen from the INTERLACE trial (NCT01566240) with the pembrolizumab-based regimen from KEYNOTE-A18 can further improve outcomes and reduce the morbidity associated with brachytherapy. Dr Shea expressed optimism about this question, citing preliminary experience suggesting that neoadjuvant chemotherapy may reduce the need for invasive radiation techniques.