The role of secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer: what do the trials tell us?
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SUBMITTER: Coleman RL
PROVIDER: S-EPMC7767661 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
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The role of secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer: what do the trials tell us?
Journal of gynecologic oncology 20201202 1
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Project description:The ovarian cancer recurrence occurs in 75% of patients with advanced FIGO stage, and its treatment is a challenge for the oncologist in gynecology. The standard treatment of recurrent ovarian cancer (ROC) usually includes intravenous chemotherapy according to platinum sensitivity. Furthermore, maintenance treatment with target therapies [e.g., anti-angiogenic drug or PARP inhibitors (PARPi)], should be provided if not precedently administrated. In this scenario, secondary cytoreductive surgery (SCS) remains a practical but controversial option for platinum-sensitive ROC (PSROC). So far, several retrospective series and a Cochrane meta-analysis had concluded that SCS could determine better survival outcomes in ROC with favorable prognostic characteristics, such as the presence of a single anatomical site of recurrence, or when patients are accurately selected for surgery based on complete resection's predictive models. Recently, three randomized clinical trials (RCTs) investigated the role of SCS in PSROC patients selected with different criteria. All the three RCTs showed a significant statistical advantage in progression-free survival (PFS) in the SCS group, with an even more significant difference in patients with complete cytoreduction (about 7-month PFS increased). Data on overall survival (OS) are different in the two completed trials. The GOG213 study has documented a longer OS of PSROC patients who received chemotherapy alone compared to surgery plus chemotherapy. Contrarily, the DESKTOP III trial showed 7.7 months of increased OS in the surgery group vs. chemotherapy alone, with a more difference in the complete tumor cytoreduction (CTC) group (12 months). These RCTs thereby suggest that undergoing complete cytoreduction may not be the only key and that the disease biology may also matter. Few recent retrospective series investigated the role of SCS according to BRCA mutation status and the effect of SCS in patients receiving emerging PARPi. A consequence of the developments in SCS and knowledge of different molecular pathways influencing the recurrent disease is that the future research objective should be to individualize and personalize the surgical approach.
| S-EPMC8039681 | biostudies-literature
Project description:BackgroundSecondary surgical cytoreduction in women with platinum-sensitive, recurrent epithelial ovarian, primary peritoneal, or fallopian-tube ("ovarian") cancer is widely practiced but has not been evaluated in phase 3 investigation.MethodsWe randomly assigned patients with recurrent ovarian cancer who had received one previous therapy, had an interval during which no platinum-based chemotherapy was used (platinum-free interval) of 6 months or more, and had investigator-determined resectable disease (to no macroscopic residual disease) to undergo secondary surgical cytoreduction and then receive platinum-based chemotherapy or to receive platinum-based chemotherapy alone. Adjuvant chemotherapy (paclitaxel-carboplatin or gemcitabine-carboplatin) and use of bevacizumab were at the discretion of the investigator. The primary end point was overall survival.ResultsA total of 485 patients underwent randomization, 240 to secondary cytoreduction before chemotherapy and 245 to chemotherapy alone. The median follow-up was 48.1 months. Complete gross resection was achieved in 67% of the patients assigned to surgery who underwent the procedure. Platinum-based chemotherapy with bevacizumab followed by bevacizumab maintenance was administered to 84% of the patients overall and was equally distributed between the two groups. The hazard ratio for death (surgery vs. no surgery) was 1.29 (95% confidence interval [CI], 0.97 to 1.72; P = 0.08), which corresponded to a median overall survival of 50.6 months and 64.7 months, respectively. Adjustment for platinum-free interval and chemotherapy choice did not alter the effect. The hazard ratio for disease progression or death (surgery vs. no surgery) was 0.82 (95% CI, 0.66 to 1.01; median progression-free survival, 18.9 months and 16.2 months, respectively). Surgical morbidity at 30 days was 9%; 1 patient (0.4%) died from postoperative complications. Patient-reported quality of life decreased significantly after surgery but did not differ significantly between the two groups after recovery.ConclusionsIn this trial involving patients with platinum-sensitive, recurrent ovarian cancer, secondary surgical cytoreduction followed by chemotherapy did not result in longer overall survival than chemotherapy alone. (Funded by the National Cancer Institute and others; GOG-0213 ClinicalTrials.gov number, NCT00565851.).
| S-EPMC6941470 | biostudies-literature
Project description:PurposeThe purpose of this phase II study was to evaluate hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin for recurrent ovarian cancer during secondary cytoreductive surgery.Materials and methodsPatients were intraoperatively randomly assigned to carboplatin HIPEC (800 mg/m2 for 90 minutes) or no HIPEC, followed by five or six cycles of postoperative IV carboplatin-based chemotherapy, respectively. Based on a binomial single-stage pick-the-winner design, an arm was considered winner if ≥ 17 of 49 patients were without disease progression at 24 months post-surgery. Secondary objectives included postoperative toxicity and HIPEC pharmacokinetics.ResultsOf 98 patients, 49 (50%) received HIPEC. Complete gross resection was achieved in 82% of the HIPEC patients and 94% of the standard-arm patients. Bowel resection was performed in 37% of patients in the HIPEC arm compared with 65% in the standard (P = .008). There was no perioperative mortality and no difference in use of ostomies, length of stay, or postoperative toxicity. At 24 months, eight patients (16.3%; 1-sided 90% CI, 9.7 to 100) were without progression or death in the HIPEC arm and 12 (24.5%; 1-sided 90% CI, 16.5 to 100) in the standard arm. With a medium follow-up of 39.5 months, 82 patients progressed and 37 died. The median progression-free survival in the HIPEC and standard arms were 12.3 and 15.7 months, respectively (hazard ratio, 1.54; 95% CI, 1 to 2.37; P = .05). There was no significant difference in median overall survival (52.5 v 59.7 months, respectively; hazard ratio, 1.39; 95% CI, 0.73 to 2.67; P = .31). These analyses were exploratory.ConclusionHIPEC with carboplatin was well tolerated but did not result in superior clinical outcomes. This study does not support the use of HIPEC with carboplatin during secondary cytoreductive surgery for platinum-sensitive recurrent ovarian cancer.
| S-EPMC8330970 | biostudies-literature
Project description:BackgroundEpithelial ovarian cancer is the leading cause of death among gynecological malignancies. Platinum resistance remains a dilemma and bottleneck in treatment, and salvage chemotherapy has limited effectiveness. Recently, the role of secondary cytoreductive surgery (SCS) in patients with platinum-resistant recurrent ovarian cancer (ROC) has caused attention especially in patients with oligometastases. However, there is neither high-quality evidence-based evidence nor standardized criteria for selecting SCS for patients with platinum-resistant ROC until now.MethodsThis multicenter, randomized, controlled clinical trial is to evaluate the value of SCS and to clarify reliable criteria of utilizing SCS in women with ROC, which is led by Gynecologic Oncology Group, Women's Hospital, Zhejiang University School of Medicine. Recruitment has started on January 1st, 2023, and is scheduled to end in December 2026. One hundred and forty participants with platinum-resistant ROC who meet the "RSCS criteria" will be randomized assigned at a ratio of 1:1 to either the experimental arm or the standard arm. Patients in the experimental arm will receive SCS followed by non-platinum single agent chemotherapy (paclitaxel, gemcitabine or liposomal adriamycin) for at least 4 cycles while patients in the standard arm will be provided with only non-platinum single agent chemotherapy. The primary outcome is progression-free survival. The secondary outcomes are overall survival, adverse events and health-related cancer-specific quality of life.Trial registrationClinicalTrials.gov Identifier: NCT05633199.
| S-EPMC10792204 | biostudies-literature
Project description:IntroductionOvarian cancer is a disease that presents in advanced stage, due to the absence of any specific or overtly dramatic symptoms. The standard of care is primary debulking surgery, followed by chemotherapy. Ovarian cancer recurrence treatment is very challenging and there is always a debate between cytoreduction vs chemotherapy.MethodsThe electronic medical records of all patients who underwent secondary cytoreductive surgery for recurrent ovarian cancer between January 2011 and December 2019 were retrieved the patients with platinum sensitive recurrent ovarian cancer who underwent secondary cytoreductive surgery in our department during this time period were included.ResultsA total of 52 patients underwent secondary cytoreductive surgery for recurrent ovarian cancer during the study period. Median treatment free interval after primary treatment was 20 months (range 6-132). The secondary cytoreductive surgery was highly complex in 4(8 %) patients,19 (37 %) had intermediate surgical complexity score, 29 (55 %) had low surgical complexity score according to the Aletti complexity score. Secondary cytoreductive surgery was complete (no macroscopic residual disease) in 31(60 %); Optimal (R1) in 17 (33 %) and suboptimal in only 4 (7 %) of the patients. Out of the 52 patients,8 expired, 16 had a second recurrence, and 10 were lost to follow up over time.ConclusionSuccessful surgery is possible in well selected patients, which in turn can lead to a meaningful progression free and overall survival benefit. Meticulous individualisation of cases should be done keeping in mind the patient's performance status, prior treatment history & toxicity; distribution & extent of disease, and the patient's overall life goals.
| S-EPMC11325282 | biostudies-literature
Project description: Not available
| S-EPMC5715461 | biostudies-literature
Project description:BackgroundAlthough rechallenge with platinum-based chemotherapy is effective for most platinum-sensitive recurrent ovarian cancer (ROC) patients, there is still a subset of patients who have no responses to the standard care. Overcoming multidrug resistance (MDR) is a top priority in oncology clinics, but it remains intricate. It is difficult for clinicians to manage unretractable ROC when conventional therapy yields no results. The rational and effective use of immunotherapy will contribute to the clinical benefit of these patients, especially in patients without approved immunotherapy biomarkers. Here we present a case of successful secondary radical surgery for unretractable metastatic MDR ROC by immunotherapy based on her immune-infiltrating tumor microenvironment signatures.Case descriptionA 57-year-old woman, diagnosed with IC2 stage high-grade serous ovarian cancer in 2015, underwent immediate ultra-radical cytoreductive surgery followed by 6 cycles of platinum-containing adjuvant chemotherapy. After nearly 37 months of disease-free status, the woman complained of spontaneous pain from the right subcostal margin for 1 month and was diagnosed with ROC accompanied by multiple unretractable colorectal and hepatic metastases. Standard chemotherapies were ineffective and quickly resulted in disease progression and grade IV myelosuppression followed impaired gastrointestinal function. Notably, after standard chemotherapy, the patient was tested negative for all immune biomarkers, but multiple fluorescence immunohistochemistry indicated that her tumor tissue was significantly infiltrated with the cluster of differentiation 8 (CD8) T cells and natural killer (NK) cells, implying potential benefits of immunotherapy. Then changed to 3 cycles of intravenous pembrolizumab, the main pelvic tumor and hepatic metastases showed significant shrinkage and achieved partial response, but the disease progressed after 8.7 months. Subsequently, arterial perfusion with pembrolizumab was performed combined with the chemotherapy. A comfortingly partial response was achieved again that enabled the patient to successfully undergo a secondary radical surgery for colorectal and liver metastases. Since that time the patient's postoperative course has been favorable, and she remains disease-free at present for at least 17 months.ConclusionsImmune infiltration signatures of the tumor microenvironment could serve as an indication for immunotherapy in patients with unretractable platinum-sensitive ROC with MDR. In addition, the introduction of immunotherapy might bring some degree of chemotherapy resensitization.
| S-EPMC9279770 | biostudies-literature
Project description:ObjectivesFDA-approved treatments for platinum-sensitive recurrent ovarian cancer (PSROC) include bevacizumab and PARP inhibitors (PARPi); clinical decisions regarding therapy must be made prior to initiating chemotherapy. Using the American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) value frameworks, we assessed relative values of concurrent/maintenance biologic therapies in PSROC.MethodsValue scores were calculated for key maintenance therapies based on randomized controlled trials: bevacizumab (OCEANS, GOG 213); olaparib (Study 19, SOLO2); niraparib (NOVA); rucaparib (ARIEL3). Personalized value scorecards were constructed for patients with germline/somatic-BRCA mutations, homologous recombination deficiency (HRD), and wild-type BRCA (wBRCA). ASCO value scores assess clinical benefit, toxicity, long-term survival, symptom palliation, treatment-free interval, and quality of life (QOL). ESMO value scores assess clinical benefit, toxicity, and QOL.ResultsASCO scores were highest for maintenance PARPi in germline/somatic-BRCA mutation cohorts: olaparib (SOLO2) = 47, (Study 19) = 62; niraparib = 50; rucaparib = 54. HRD cohorts had slightly lower scores: niraparib = 46; rucaparib = 37. wBRCA cohorts had the lowest scores: niraparib = 26; rucaparib = 26; and olaparib (Study 19) = 32, as did patients receiving bevacizumab (OCEANS) = 35, (GOG 213) = 26. ESMO scores demonstrated high-value for maintenance PARPi in germline/somatic-BRCA mutation cohorts and low-value for bevacizumab and PARPi in wBRCA cohorts.ConclusionsThe value of maintenance PARPi therapy depends heavily on BRCA status, with the highest value scores in germline/somatic-BRCA mutation cohorts. Personalized value scorecards provide a visual aid to assess the harm-benefit balance of maintenance PARPi for PSROC.
| S-EPMC7522787 | biostudies-literature
Project description:Ovarian cancer is a leading cause of death from gynecological cancers worldwide. Platinum-based chemotherapy provides the cornerstone of the medical management. In first line and subsequent relapses, maintenance strategies are offered to prolong intervals between lines of chemotherapy. Current maintenance options involve bevacizumab and poly ADP-ribose polymerase inhibitors, but these lines of therapy can only be used once in the disease course. Patients in first or second platinum sensitive relapse after poly ADP-ribose polymerase inhibitors and bevacizumab represent an area of unmet medical need. This academic sponsored, international Phase II randomized trial is evaluating the combination of a therapeutic cancer vaccine (OSE2101) with anti-PD1 (pembrolizumab) as maintenance therapy, in patients with platinum-sensitive recurrence regardless of number of prior lines and no progression after platinum-based chemotherapy.Clinical Trial Registration: NCT04713514 (ClinicalTrials.gov).
| S-EPMC11572149 | biostudies-literature
Project description:Epithelial ovarian cancer (OC) is a common gynecologic malignancy in women. The standard treatment for OC is maximal cytoreductive surgical debulking followed by platinum-based chemotherapy. Despite the high response rate to primary therapy, approximately 85% of patients will develop recurrent ovarian cancer (ROC). This review identifies the clinical use of trabectedin in the treatment algorithm for ROC, with specific emphasis on platinum-sensitive ROC, for which trabectedin in combination with pegylated liposomal doxorubicin has been approved as a treatment protocol. The main mechanisms of action of trabectedin at the cellular level and in the tumor microenvironment is also discussed as bases for identifying biomarkers for selecting patients who may largely benefit from trabectedin-based therapies.
| S-EPMC4302088 | biostudies-literature