Yanling Feng

Surgery versus no surgery in platinum-sensitive relapsed ovarian cancer: final overall survival analysis of the SOC-1 randomized phase 3 trial

Surgery for platinum-sensitive, relapsed ovarian cancer (PSROC) is widely practiced but had contradictory survival outcomes in previous studies. In this multicenter, open-label, phase 3 trial, women with PSROC, and having had one previous therapy and no platinum-based chemotherapy (platinum-free interval) of 6 months or more, were randomly assigned to either the surgery group (182 patients) or the no-surgery group (control) (175 patients). Patients with resectable diseases were eligible according to the international model (iMODEL), combined with a positron emission tomography-computed tomography imaging. Overall survival (OS) and progression-free survival were coprimary endpoints in hierarchical testing, and a significantly longer progression-free survival with surgery was previously reported. Final analysis of OS was planned at data maturity of 59%. Between 19 July 2012 and 3 June 2019, 357 patients were enrolled. Median follow-up was 82.5 months. Median OS was 58.1 months with surgery and 52.1 months for control (hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.61-1.05, P = 0.11). The predefined threshold for statistical significance was not met, but prespecified sensitivity analysis was performed. Overall, 61 of 175 (35%) patients in control had crossed over to surgery following subsequent relapse, and adjusted HR for death in the surgery group compared with control was 0.76, 95% CI 0.58-0.99. In subgroup analysis of relapse sites by imaging, median survival was not estimable in the surgery group and was 69.5 months in control in patients with 60 months in the surgery group as compared with five of 175 (2.9%) patients in the control group. In patients with PSROC, surgery did not increase OS in the intention-to-treat population but resulted in a prolongation of survival following adjustment of crossover.ClinicalTrials.gov registration: NCT01611766 .

Sentinel-Lymph-Node Biopsy Alone or with Lymphadenectomy in Cervical Cancer

Limited data are available on survival outcomes after sentinel-lymph-node biopsy alone as compared with lymphadenectomy in cervical cancer. In this multicenter, randomized, noninferiority trial, we enrolled patients with cervical cancer that was stage IA1 (with lymphovascular invasion), IA2, IB1, or IIA1 according to 2009 International Federation of Gynecology and Obstetrics criteria. Sentinel-lymph-node biopsy was performed at the time of surgery and was followed by examination of frozen sections. Patients who had negative sentinel lymph nodes were intraoperatively assigned in a 1:1 ratio not to undergo pelvic lymphadenectomy (the biopsy-only group) or to undergo lymphadenectomy (the lymphadenectomy group). All the patients underwent hysterectomy, and adjuvant therapy was provided according to a unified protocol. The primary end point was disease-free survival at 3 years, with a prespecified noninferiority margin of 5 percentage points in the upper limit of the confidence interval for the difference between the lymphadenectomy group and the biopsy-only group. Secondary end points included retroperitoneal nodal recurrence, cancer-specific survival, and surgical complications. A total of 838 patients underwent randomization: 420 patients were assigned to the biopsy-only group and 418 to the lymphadenectomy group. The median follow-up was 62.8 months. The 3-year disease-free survival was 94.6% in the lymphadenectomy group and 96.9% in the biopsy-only group (difference, -2.3 percentage points; 95% confidence interval [CI], -5.0 to 0.5; P<0.001 for noninferiority); the 3-year cancer-specific survival was 99.2% in the biopsy-only group and 97.8% in the lymphadenectomy group (hazard ratio for death from cancer in competing-risks analysis, 0.37; 95% CI, 0.15 to 0.95). Retroperitoneal nodal recurrences occurred in no patients in the biopsy-only group and in 9 patients (2.2%) in the lymphadenectomy group. The biopsy-only group had a lower incidence of lymphocyst than the lymphadenectomy group (8.3% vs. 22.0%; P<0.001), as well as a lower incidence of lymphedema (5.2% vs. 19.1%; P<0.001), paresthesia (4.0% vs. 8.4%; P = 0.009), and pain (2.6% vs. 7.9%; P = 0.001). In patients with early-stage cervical cancer, sentinel-lymph-node biopsy alone was noninferior to lymphadenectomy with respect to disease-free survival and was associated with fewer complications. (Funded by Guangzhou Municipal Science and Technology and others; PHENIX ClinicalTrials.gov number, NCT02642471.).

A phase II trial of cytoreductive surgery combined with niraparib maintenance in platinum-sensitive, secondary recurrent ovarian cancer: SGOG SOC-3 study

In China, secondary cytoreductive surgery (SCR) has been widely used in ovarian cancer (OC) over the past two decades. Although Gynecologic Oncology Group-0213 trial did not show its overall survival benefit in first relapsed patients, the questions on patient selection and effect of subsequent targeting therapy are still open. The preliminary data from our pre-SOC1 phase II study showed that selected patients with second relapse who never received SCR at recurrence may still benefit from surgery. Moreover, poly(ADP-ribose) polymerase inhibitors (PARPi) maintenance now has been a standard care for platinum sensitive relapsed OC. To our knowledge, no published or ongoing trial is trying to answer the question if patient can benefit from a potentially complete resection combined with PARPi maintenance in OC patients with secondary recurrence. SOC-3 is a multi-center, open, randomized, controlled, phase II trial of SCR followed by chemotherapy and niraparib maintenance vs chemotherapy and niraparib maintenance in patients with platinum-sensitive second relapsed OC who never received SCR at recurrence. To guarantee surgical quality, if the sites had no experience of participating in any OC-related surgical trials, the number of recurrent lesions evaluated by central-reviewed positron emission tomography-computed tomography image shouldn't be more than 3. Eligible patients are randomly assigned in a 1:1 ratio to receive either SCR followed by 6 cycles of platinum-based chemotherapy and niraparib maintenance or 6 cycles of platinum-based chemotherapy and niraparib maintenance alone. Patients who undergo at least 4 cycles of chemotherapy and must be, in the opinion of the investigator, without disease progression, will be assigned niraparib maintenance. Major inclusion criteria are secondary relapsed OC with a platinum-free interval of no less than 6 months and a possibly complete resection. Major exclusion criteria are borderline tumors and non-epithelial ovarian malignancies, received debulking surgery at recurrence and impossible to complete resection. The sample size is 96 patients. Primary endpoint is 12-month non-progression rate. ClinicalTrials.gov Identifier: NCT03983226.

The impact of lymph node dissection on survival in patients with clinical early-stage ovarian cancer

To estimate the impact of lymph node dissection on survival in patients with apparent early-stage epithelial ovarian cancer (EOC). We conducted a retrospective review of patients with clinical stage I-II EOC. All patients underwent primary surgery at Sun Yat-sen University Cancer Center between January 2003 and December 2015. Demographic features and clinicopathological information as well as perioperative adverse events were investigated, and survival analyses were performed. A total of 400 ovarian cancer patients were enrolled, and patients were divided into 2 groups: 81 patients did not undergo lymph node resection (group A), and 319 patients underwent lymph node dissection (group B). In group B, the median number of removed nodes per patient was 25 (21 pelvic and 4 para-aortic nodes). In groups A and B, respectively, the 5-year progression-free survival (PFS) rates were 83.3% and 82.1% (p=0.305), and the 5-year overall survival (OS) rates were 93.1% and 90.9% (p=0.645). The recurrence rate in the retroperitoneal lymph nodes was not associated with lymph node dissection (p=0.121). The median operating time was markedly longer in group B than in group A (220 minutes vs. 155 minutes, p<0.001), and group B had a significantly higher incidence of lymph cysts at discharge (32.9% vs. 0.0%, p<0.001). In patients with early-stage ovarian cancer, lymph node dissection was not associated with a gain in OS or PFS and was associated with an increased incidence of perioperative adverse events.

Perineural Invasion Should Be Regarded as an Intermediate-Risk Factor for Recurrence in Surgically Treated Cervical Cancer: A Propensity Score Matching Study

Background. Perineural invasion (PNI) is considered as a poor prognostic factor in cervical cancer, but there has been no postoperative adjuvant therapy for it, because whether it belongs to high- or intermediate-risk factors has not been determined, this study intends to provide evidences to solve this problem. Methods. We conducted a retrospective analysis of cervical cancer patients who underwent radical surgery and be reported PNI from January 2012 to June 2017 at the Sun Yat-sen University Cancer Center. After 1 : 1 propensity score matching (PSM), a group of patients without PNI was matched according to the clinical pathological features. Postoperative pathological parameters and prognosis were evaluated between the PNI and the matched groups. Results. 1836 patients were screened, of which 162 (8.8%) diagnosed as stages IB1 to IIB reported PNI. Comparing to the matched group, more PNI (+) patients had deep outer cervix stromal invasion, cervical tunica adventitia invasion, positive lymph nodes, and positive margins. Among patients without high-risk factors, PNI (+) patients had worse 3-year overall survival (90.8% vs. 98.1%, P = 0.02 ), PNI (+) patients with single intermediate-risk factor and PNI (-) patients who meet with SEDLIS criteria had similar progress free survival ( P = 0.63 ) and overall survival ( P = 0.63 ), even similar survival curves. Conclusion. PNI is related to a worse overall survival among cervical cancer patients without high-risk factors and play the role as an intermediate-risk factor.

QL1604 plus paclitaxel-cisplatin/carboplatin in patients with recurrent or metastatic cervical cancer: an open-label, single-arm, phase II trial

QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46). The median duration of response was 9.6 months (95% confidence interval [CI]=5.5-not estimable). The median progression-free survival was 8.1 months (95% CI=5.7-14.0). Forty-five (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can't tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

Surgery and Niraparib in Secondary Recurrent Ovarian Cancer (SOC-3 Trial)

This is a Phase II, open-label, multicenter, randomized umbrella study to evaluate the efficacy of cytoreductive surgery and Niraparib maintenance in participants with platinum-sensitive secondary recurrent ovarian cancer. Cohort 1 will focus on participants without prior use of PARP inhibitor, and without prior secondary cytoreduction (SCR) when first recurrence. Cohort 2 will focus on participants with prior use of PARP inhibitor, but without prior SCR when first recurrence. Cohort 3 will focus on participants with SCR when first recurrence, but without prior use of PARP inhibitor.

Sentinel Lymph Node Biopsy Versus Pelvic Lymphadenectomy in Early-stage Cervical Cancer (PHENIX/CSEM 010)

The diagnostic value of sentinel lymph node biopsy in early-stage cervical cancer has been well studied. However, there were no randomized controlled study on comparing the long-term outcomes of sentinel lymph node biopsy and conventional procedure. The investigators perform a phase III, randomized controlled trial to determine whether pelvic lymphadenectomy can be replaced by sentinel lymph node biopsy in surgical treatment for patients with early-stage cervical cancer.

Surgery or Chemotherapy in Recurrent Ovarian Cancer (SOC 1 Trial)?

The purpose of this study is to evaluate the role of secondary cytoreduction (SCR) and validate the risk model of patient selection criteria in platinum-sensitive recurrent ovarian cancer.