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Purpose: Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease., Methods: This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control., Results: Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P = .003) and durvalumab + olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P < .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42 [95% CI, 0.22 to 0.80]; HR [durvalumab + olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95% CI, 0.60 to 0.97]; HR [durvalumab + olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1-positive subgroups (HR [durvalumab v control], 0.63 [95% CI, 0.48 to 0.83]; HR [durvalumab + olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77 [95% CI, 0.56 to 1.07]; P = .120; durvalumab + olaparib v control: HR, 0.59 [95% CI, 0.42 to 0.83]; P = .003). The safety profiles of the experimental arms were generally consistent with individual agents., Conclusion: Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer.

Introduction: The traditional approach to patients with ovarian cancer is cytoreductive surgery and surgical staging through a vertical midline laparotomy. While laparoscopy has become an integral part of gynecologic surgery, debulking procedures have not been feasible to date with standard minimally invasive techniques., Methods and Materials: Twenty-five patients with ovarian carcinoma underwent surgical staging and cytoreduction using hand-assisted laparoscopy. We review the surgical technique and clinical outcomes., Results: Twenty-five patients were managed during this study time frame with hand-assisted laparoscopy. Six patients had apparent advanced stage ovarian cancer at the time of referral, and 17 patients had apparent early-stage ovarian cancer. Of the 19 patients with presumed early-stage disease, 5 patients were upstaged based on retroperitoneal lymph node involvement, 3 with disease to other pelvic structures, and 2 patients had microscopic disease in the omentum. Twenty-two patients had their surgeries completed via hand-assisted laparoscopy, and three cases required conversion to laparotomy for completion of debulking surgery. Complication rates were low with three complications requiring reoperation or hospitalization. The mean hospital stay was 1.8 days for the 22 patients who had a successful hand-assisted laparoscopic evaluation. Operating times were variable and ranged from 81 to 365 min., Conclusion: Hand-assisted laparoscopy may be employed in the initial management of early and advanced stage ovarian carcinoma. This approach allows for thorough evaluation of peritoneal and retroperitoneal structures and surgical cytoreduction while retaining the advantages of minimally invasive surgery.

Background: Large cell neuroendocrine cervical carcinoma is a rare malignancy. These tumors appear to mimic the aggressive behavior of small cell neuroendocrine tumors. Metastasis and recurrent disease are common. Due to the low incidence of these tumors, optimal therapy has not been delineated., Cases: Two patients presented with large cell neuroendocrine cervical carcinoma, stage IB1 and IIA, at our institution from 1997 to 1999. We describe the clinical course for these two patients and review the relevant literature for the management of large cell cervical carcinoma., Conclusion: Unlike squamous cell carcinoma, early-stage large cell neuroendocrine tumors of the cervix are aggressive. Disease recurrences are frequent and distant metastasis is common. Multimodal therapy should be considered at the time of initial diagnosis., (Copyright 2001 Academic Press.)

Genetic analysis of cervical cancer has demonstrated frequent allelic loss in the 3p chromosomal region. The newly described gene FHIT is located at chromosome region 3p14.2, and its expression has been demonstrated previously by reverse transcription-PCR to be abnormal in a majority of cervical cancer cell lines. In this study, 98 different lesions of the cervix were examined for Fhit expression by immunohistochemical staining. Whereas normal cervical epithelium demonstrated diffuse, moderate to intense cytoplasmic staining, many pathological lesions of the cervix displayed reduced or absent Fhit expression. Sixty-one percent of squamous carcinomas and 40% of adenocarcinomas of the cervix had abnormal Fhit expression. Sixty-five preneoplastic lesions of the cervix were examined. Eleven of 33 high-grade squamous intraepithelial lesions and 1 of 12 low-grade squamous intraepithelial lesions had abnormal Fhit expression. In summary, Fhit expression is frequently abnormal in both glandular and squamous cervical cancers, with a higher frequency of Fhit alterations observed in squamous lesions. In addition, abnormal Fhit expression can be detected in some preneoplastic lesions of the ectocervix. Alterations in Fhit expression may be an important marker of early progression in the development of cancers of the cervix.