Investigator
Memorial Sloan Kettering Cancer Center
Bifunctional Blockade: A Novel Immunotherapy Approach for Cervical Cancer
Summary SHR-1701, a bispecific fusion protein directed against PD-L1 and TGFβ, demonstrates promising clinical activity in advanced/recurrent cervical cancer. A recent study serves as a proof of principle that the TGFβ pathway may be successfully targeted, and that bispecific antibodies offer a novel therapeutic approach to do so. See related article by Feng et al., p. 5297
Assessing the Genomic Landscape of Cervical Cancers: Clinical Opportunities and Therapeutic Targets
Abstract Purpose: Tumor genomic profiling is increasingly used to guide treatment strategy in patients with cancer. We integrated tumor genomic, clinical demographic, and treatment response data to assess how prospective tumor-normal sequencing impacted treatment selection in patients with cervical cancer. Experimental Design: Cervical cancers were prospectively analyzed using the MSK-IMPACT (Memorial Sloan Kettering Cancer Center – Integrated Mutation Profiling of Actionable Cancer Targets) next-generation sequencing panel. Clinical data, including histology, stage at diagnosis, treatment history, clinical trial enrollment and outcomes, date of last follow-up, and survival status were obtained from medical records. Results: A total of 177 patients with cervical cancer (squamous, 69; endocervical adenocarcinoma, 50; gastric type, 22; adenosquamous, 21; and other, 15) underwent MSK-IMPACT testing. The most prevalent genomic alterations were somatic mutations or amplifications in PIK3CA (25%), ERBB2 (12%), KMT2C (10%), and KMT2D (9%). Furthermore, 13% of patients had high tumor mutational burden (TMB >10 mut/Mb), 3 of which were also microsatellite instability–high (MSI-H). Thirty-seven percent of cases had at least one potentially actionable alteration designated as a level 3B mutational event according to the FDA-recognized OncoKB tumor mutation database and treatment classification system. A total of 30 patients (17%) were enrolled on a therapeutic clinical trial, including 18 (10%) who were matched with a study based on their MSK-IMPACT results. Twenty patients (11%) participated in an immune checkpoint inhibition study for metastatic disease; 2 remain progression free at >5 years follow-up. Conclusions: Tumor genomic profiling can facilitate the selection of targeted/immunotherapies, as well as clinical trial enrollment, for patients with cervical cancer.
RELEVANT-C study: patient-reported prevalence of lower extremity lymphedema after sentinel lymph node mapping vs lymphadenectomy after surgery for early-stage cervical cancer
To compare the prevalence of patient-reported lower extremity lymphedema and evaluate patient-reported quality of life after sentinel lymph node mapping vs comprehensive lymphadenectomy with or without sentinel lymph node mapping for the surgical management of early-stage cervical cancer. In July 2022, we mailed a survey that included a validated 13-item lower extremity lymphedema screening questionnaire to patients who underwent lymph node evaluation at the time of primary surgery for the 2018 International Federation of Gynecology and Obstetrics stage IA1 to IIB cervical cancer between January 1, 2006, and January 31, 2019. We excluded patients diagnosed with lower extremity lymphedema prior to surgery and those who answered ≤6 survey items, and we carried out 2 group comparisons: sentinel lymph node mapping vs lymphadenectomy with or without sentinel lymph node mapping, and patients with lower extremity lymphedema vs patients without. Of 459 potential participants, 90 (20%) responded to the survey, all of which were evaluable (37 sentinel lymph nodes; 53 lymphadenectomies ± sentinel lymph nodes). Self-reported lower extremity lymphedema prevalence was 10.8% (4/37) in the sentinel lymph node mapping group and 43.4% (23/53) in the lymphadenectomy with or without sentinel lymph node mapping group (OR 6.32, 95% CI 2.14 to 23.5, p = .002). Histologic subtype and number of lymph nodes removed were associated with increased prevalence of lower extremity lymphedema. After adjusting for the histology subtype, lymphadenectomy retained independent association with an increased prevalence of lower extremity lymphedema over sentinel lymph node mapping (OR 4.96, 95% CI 1.61 to 18.8, p = .009). Patients with self-reported lower extremity lymphedema had significantly worse quality of life compared to those without self-reported lower extremity lymphedema. We found sentinel lymph node mapping to be independently associated with a significantly decreased prevalence of patient-reported lower extremity lymphedema and with improved quality of life in patients undergoing surgical management of early-stage cervical cancer.
