Pembrolizumab Plus Chemotherapy for Advanced and Recurrent Cervical Cancer: Final Analysis According to Bevacizumab Use in the Randomized KEYNOTE-826 Study.

BACKGROUND: In KEYNOTE-826 (NCT03635567), pembrolizumab plus chemotherapy (± bevacizumab) significantly improved overall survival (OS) and progression-free survival (PFS) in patients with persistent, recurrent, or metastatic cervical cancer. This exploratory analysis examined outcomes in patient subgroups defined by bevacizumab use. PATIENTS AND METHODS: Eligible adult patients had persistent, recurrent, or metastatic squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix not previously treated with chemotherapy and not amenable to curative treatment; measurable disease per RECIST v1.1; and an Eastern Cooperative Oncology Group performance status ≤1. Patients were randomized 1:1 to pembrolizumab 200 mg every 3 weeks or placebo for up to 35 cycles plus chemotherapy (± bevacizumab 15 mg/kg). Dual primary endpoints were OS and PFS per RECIST v1.1 by investigator assessment. Outcomes were assessed in subgroups defined by bevacizumab use. Hazard ratios (HRs) and 95% CIs were based on a stratified Cox regression model. RESULTS: 617 patients were randomized (pembrolizumab arm, n=308 [63.6% with bevacizumab]; placebo arm, n=309 [62.5% with bevacizumab]). The most common reason for bevacizumab exclusion was medical contraindication (75.9%). Among patients who received bevacizumab, HRs (95% CIs) for PFS favored the pembrolizumab arm in the PD-L1 combined positive score (CPS) ≥1 (0.56 [0.43-0.73]) and all-comer (0.57 [0.45-0.73]) populations; OS results were 0.60 (0.45-0.79) and 0.61 (0.47-0.80), respectively. Among patients who did not receive bevacizumab, HRs (95% CIs) for PFS also favored the pembrolizumab arm in the PD-L1 CPS≥1 (0.61 [0.44-0.85]) and all-comer (0.69 [0.50-0.94]) populations; OS results were 0.61 (0.44-0.85) and 0.67 (0.49-0.91), respectively. Among patients who received bevacizumab, grade ≥3 treatment-related adverse events occurred in 74.0% of patients in the pembrolizumab arm and 66.8% in the placebo arm. CONCLUSION: Pembrolizumab plus chemotherapy prolonged PFS and OS and had manageable safety compared with placebo plus chemotherapy in patient subgroups defined by bevacizumab use.

[Are there still contra-indications to laparoscopic treatment of endometrial carcinoma?]. / Y a-t-il encore des contre-indications à la laparoscopie dans le traitement chirurgical des cancers de l'endomètre?

Laparoscopic treatment is becoming a standard of care for early endometrial carcinoma. However, not all patients are suitable for this approach. A review of the current literature provides some arguments to differentiate absolute contra-indications from relative ones, for which, whenever possible, some options are suggested.

Measurement of mRNA of 11 biomarkers by RT-PCR to detect lymph node involvement in cervical cancer.

Lymph node metastases are a major prognostic factor in cervical carcinomas. The aim of this study was to characterize the expression of 11 markers in cervical tumors and negative lymph nodes and to determine which ones could be helpful for improving the specificity of molecular diagnosis of nodal involvement. Using TaqMan RT-PCR, we studied the expression of CK19, MUC1, HER1-HER4, VEGF, VEGF-C, uPA, MMP9, and PRAD1 in uterine cervical tumors and in histologically nonmetastatic lymph nodes of 8 patients diagnosed with locally advanced cervical cancer. We observed that CK19, MUC1, HER1-HER3, uPA, and VEGF had a significantly higher expression in cervical tumors than in the negative nodes, whereas VEGF-C expression level was higher in the negative nodes than in the tumors. PRAD1 harbored similar expression levels in the tumors and in the negative nodes. Interestingly, 1 of the 4 patients who presented a clinical recurrence, showed elevated HER1, HER2, uPA, and VEGF in the histologically negative nodes. Our results suggest that CK19, MUC1, HER1-3, uPA, and VEGF are biomarkers that have a higher expression in tumoral cervical tissues compared with the negative lymph nodes and could be useful to diagnose nodal involvement in uterine cervical carcinoma. Our results should encourage us in continue to investigate a greater number of patients, including patients with histologically involved nodes.

[Pregnancy and hemodialysis]. / Grossesse en hémodialyse chronique.

Pregnancy is a rare occurrence in patients on chronic hemodialysis (CHD). The rate of successful pregnancies amounts to almost 60%, thanks to modifications of the dialysis schedule and a specifically adapted obstetrical and neonatal management. We report on seven pregnancies occurring between 1995 and 2001 in six women with a mean age of 32 years (22-39 years), on HD for a mean period of 36 months (12-96 months). Maternal and fetal complications, and the long-term outcome of mothers and children are reported, and the collaborative approaches adopted by obstetrician, pediatrician and nephrologist are discussed. The frequency and length of HD was systematically increased. One patient chose to terminate her pregnancy at 20 weeks of gestation. The mean gestational age for the six other pregnancies was 31 weeks (24-34 weeks) with an average weight at birth of 1495 g (660-1920 g). One neonate born at 24 weeks died 2 days following delivery. One patient was treated with uterine artery embolization for post-partum haemorrhage. Pediatric evaluation of the five children, who were followed up for a period ranging between 2.5 to 5.5 years, showed a good long-term outcome. In conclusion, pregnancy needs not be counterindicated or systematically terminated in patients on CHD, particularly if transplantation is not possible, if the patient refuses it, or if she is relatively old and there is a long waiting period before transplantation.

Chemosensitivity and radiosensitivity profiles of four new human epithelial ovarian cancer cell lines exhibiting genetic alterations in BRCA2, TGFbeta-RII, KRAS2, TP53 and/or CDNK2A.

To address the cellular basis for the response to ovarian cancer treatment, we characterized the chemosensitivity and radiosensitivity of four human epithelial ovarian cancer cell lines that harbor different genetic alterations. The TOV-21G, TOV-81D, OV-90, and TOV-112D cell lines were derived from ovarian tumors (TOV) or ascites (OV) from chemotherapy- and radiotherapy-naive patients and were characterized by their mutation spectrum of BRCA2, TGFbeta-RII, KRAS2, TP53, and CDKN2A. Cells were monitored for survival following exposure at various concentrations to different cytotoxic agents including cisplatin, camptothecin or paclitaxel or to different doses of gamma-irradiation. At the lowest doses, the TGFbeta-RII-mutated and KRAS2-mutated cell line, TOV-21G, and the BRCA2-mutated cell line, TOV-81D, demonstrated a significantly higher sensitivity to cisplatin and gamma-irradiation than the TP53-mutated cell lines, TOV-112D and OV-90. At higher doses, differences between the TP53-mutated lines were observed with TOV-112D being less sensitive to cisplatin than OV-90 that also harbors a CDNK2A mutation. All cell lines were similarly sensitive to high doses of gamma-irradiation. In contrast, sensitivity to camptothecin or paclitaxel was not significantly different between all cell lines, irrespective of the mutation status of BRCA1, BRCA2, TGFbeta-RII, KRAS2, TP53, and CDKN2A. The observed responses to treatment are consistent with the current knowledge concerning BRCA2, TGFbeta-RII, KRAS2, TP53, and/or CDKN2A aberrant function.