Comparison of dose-dense vs. 3-weekly paclitaxel and carboplatin in the first-line treatment of ovarian cancer in a propensity score-matched cohort

Abstract Background Benefit of carboplatin and dose-dense weekly paclitaxel (ddCT) in first line treatment of ovarian cancer patients has been different in Western and Asian studies. In the present study we compare progression-free survival (PFS) of ddCT to three-weekly carboplatin and paclitaxel (CT) in first-line treatment of ovarian carcinoma in a single institution in a Western population. Materials and methods We conducted a retrospective review of medical records from patients with ovarian carcinoma treated in a tertiary cancer center from 2007 to 2018. All patients treated with ddCT or CT in the first-line setting were included. Patients who received first-line bevacizumab were not included. PFS and overall survival (OS) were compared in a propensity score-matched cohort to address selection bias. Patients were matched according to age, ECOG performance status, CA 125, FIGO stage, residual disease, and histological subtype, in a 1:2 ratio. Results Five hundred eighty-eight patients were eligible for propensity score matching, the final cohort consisted of 69 patients treated with ddCT and 138 CT group. Baseline characteristics were well-balanced. After a median follow-up of 65.1 months, median PFS was 29.3 vs 20.0 months, favouring ddCT treatment (p = 0.035). In the multivariate cox regression ddCT showed a 18% lower risk of progression (HR 0.82, 95% CI 0.68–0.99, p = 0.04). Overall survival data is immature, but suggested better outcomes for ddCT (not reached versus 78.8 months; p = 0.07). Conclusion Our retrospective study has shown superior PFS of ddCT over CT regimen in first-line treatment of ovarian carcinoma in a Western population not treated with bevacizumab.

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Dose-dense carboplatin and paclitaxel versus three weekly regimen in the first-line treatment of ovarian carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e18059 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e18059-e18059

Author(s):

Rafaela Pirolli ◽

Felipe Leonardo Estati ◽

Viviane Alencar ◽

Mariana Romero de Oliveira ◽

Adriana Regina Goncalves Ribeiro ◽

...

Keyword(s):

Overall Survival ◽

Propensity Score ◽

Ovarian Carcinoma ◽

Residual Disease ◽

Serous Carcinoma ◽

Matched Cohort ◽

Line Treatment ◽

First Line ◽

Dose Dense ◽

First Line Treatment

e18059 Background: The benefit of dose dense chemotherapy (ddCT) in the adjuvant treatment of ovarian carcinoma (OC) is not clear. There is one positive Japanese trial and two negative trials in non-Asian patients, which differed from the JGOG 3016 trial for the use of bevacizumab in one of them and the use of neoadjuvant CT (NCT) in half the patients in the other. In this study, we aimed to compare progression free survival (PFS) of ddCT to conventional regimen. Methods: We did a retrospective review of medical records from patients with OC treated in a Brazilian cancer center from 2007 to 2018. All patients treated with ddCT or conventional carboplatin and paclitaxel regimen (3wCT) in the first line setting were included. PFS and overall survival (OS) were compared. To address selection bias we performed a second analysis in a propensity score matched cohort. Patients were matched according to age, ECOG performance status, CA 125, stage, residual disease and histological subtype, in a 1:2 ratio. Results: A total of 615 cases were enrolled for analysis, 62 were treated with ddCT. Patients treated with ddCT presented better ECOG and more frequently presented advanced stage, high-grade serous carcinoma and residual disease ≤ 1cm. Only 10% of patients were treated with NCT in both groups. In the multivariate analysis ddCT showed a non-significant benefit over conventional CT (PFS HR 0.646, 95% CI 0.384–1.087, p = 0.10). In the propensity score matched cohort 186 patients were included, 62 treated with ddCT and 124 3wCT. Groups were well balanced. After a median follow-up of 48.1 months, median PFS was 32 (18-45.9) versus 22.7 (18.8-26.6) months, favoring dose dense treatment (p = 0.059). In the multivariate cox regression ddCT showed a 45% lower risk of progression (HR 0.55, 95% CI 0.35–0.88, p = 0.01). Overall survival data is immature, but suggested better outcomes for ddCT (NR versus 76.1 months; p = 0.02). Conclusions: There is no prospective study in a Western population with the same design as the JGOG 3016 trial. In our study, in a population with the same treatment schedules of the Japanese trial, ddCT was associated with longer PFS. This finding suggests that a weekly regimen of paclitaxel might still be a reasonable option for first-line treatment for women with advanced ovarian cancer, and should be further prospectively evaluated.

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Phase II trial of bevacizumab with carboplatin and dose-dense paclitaxel as first-line treatment in patients with advanced ovarian cancer

Gynecologic Oncology ◽

10.1016/j.ygyno.2015.01.194 ◽

2015 ◽

Vol 137 ◽

pp. 79

Author(s):

N.D. Fleming ◽

R.L. Coleman ◽

C.S. Tung ◽

M.F. Munsell ◽

A.K. Sood

Keyword(s):

Ovarian Cancer ◽

Phase Ii ◽

Phase Ii Trial ◽

Advanced Ovarian Cancer ◽

Line Treatment ◽

First Line ◽

Dose Dense ◽

First Line Treatment

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Discordance of clinical symptoms and electrophysiologic findings in taxane plus platinum-induced neuropathy

International Journal of Gynecological Cancer ◽

10.1111/j.1525-1438.2006.00766.x ◽

2007 ◽

Vol 17 (2) ◽

pp. 394-397 ◽

Cited By ~ 4

Author(s):

Y. Pan ◽

M.-S. Kao

Keyword(s):

Ovarian Cancer ◽

Ovarian Carcinoma ◽

Nerve Conduction Study ◽

Nerve Conduction ◽

Clinical Symptoms ◽

Sensory Neuropathy ◽

Line Treatment ◽

First Line ◽

Recurrent Cancer ◽

First Line Treatment

Paclitaxel combined with carboplatin is currently accepted as the first-line treatment for ovarian carcinoma, frequently associated with neuropathy. Due to its frequent association with neuropathy, combination of docetaxel and carboplatin has been suggested as an alternative. A 47-year-old woman developed paresthesia after the first cycle of paclitaxel/carboplatin for ovarian cancer. Her nerve conduction study (NCS) showed only sural neuropathy after completion of six cycles, which returned to normal in 6 months. She had fewer neuropathy symptoms when treatment was changed to docetaxel/carboplatin for recurrent cancer. NCS revealed generalized sensory neuropathy following docetaxel/carboplatin treatment, which normalized after 12 months. Our observation indicated that there is a disparity between clinical symptoms and electrophysiologic examination in taxane-induced neuropathy. Although docetaxel was tolerated well by the patient, evidence of generalized sensory neuropathy was present in NCS

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Assessment of Progression-Free Survival as a Surrogate End Point of Overall Survival in First-Line Treatment of Ovarian Cancer

JAMA Network Open ◽

10.1001/jamanetworkopen.2019.18939 ◽

2020 ◽

Vol 3 (1) ◽

pp. e1918939 ◽

Cited By ~ 4

Author(s):

Xavier Paoletti ◽

Liz-Anne Lewsley ◽

Gennaro Daniele ◽

Adrian Cook ◽

Nozomu Yanaihara ◽

...

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

Progression Free Survival ◽

Line Treatment ◽

First Line ◽

Free Survival ◽

End Point ◽

First Line Treatment

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Intensive sequential dose dense chemotherapy with stem cell support as first-line treatment in advanced ovarian carcinoma: a phase II study

Bone Marrow Transplantation ◽

10.1038/sj.bmt.1703762 ◽

2002 ◽

Vol 30 (12) ◽

pp. 879-884 ◽

Cited By ~ 4

Author(s):

F Viret ◽

F Bertucci ◽

D Genre ◽

G Gravis ◽

C Chabannon ◽

...

Keyword(s):

Stem Cell ◽

Ovarian Carcinoma ◽

Phase Ii ◽

Phase Ii Study ◽

Line Treatment ◽

First Line ◽

Stem Cell Support ◽

Dose Dense ◽

Cell Support ◽

First Line Treatment

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Comparison of endostatin combined with PT-DC versus bevacizumab combined with PT-DC in the first-line treatment of advanced lung adenocarcinoma: a retrospective propensity score- matched cohort study

Annals of Palliative Medicine ◽

10.21037/apm-21-1401 ◽

2021 ◽

Vol 0 (0) ◽

pp. 0-0

Author(s):

Xiaoling Chen ◽

Jun Nie ◽

Ling Dai ◽

Weiheng Hu ◽

Jie Zhang ◽

...

Keyword(s):

Cohort Study ◽

Propensity Score ◽

Lung Adenocarcinoma ◽

Matched Cohort ◽

Line Treatment ◽

First Line ◽

Matched Cohort Study ◽

First Line Treatment

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Phase II trial of bevacizumab with dose-dense paclitaxel as first-line treatment in patients with advanced ovarian cancer

Gynecologic Oncology ◽

10.1016/j.ygyno.2017.07.137 ◽

2017 ◽

Vol 147 (1) ◽

pp. 41-46 ◽

Cited By ~ 8

Author(s):

Nicole D. Fleming ◽

Robert L. Coleman ◽

Celestine Tung ◽

Shannon N. Westin ◽

Wei Hu ◽

...

Keyword(s):

Ovarian Cancer ◽

Phase Ii ◽

Phase Ii Trial ◽

Advanced Ovarian Cancer ◽

Line Treatment ◽

First Line ◽

Dose Dense ◽

First Line Treatment

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Bevacizumab, carboplatin, and paclitaxel in the first line treatment of advanced ovarian cancer patients: the phase IV MITO-16A/MaNGO-OV2A study

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2021-002434 ◽

2021 ◽

pp. ijgc-2021-002434

Author(s):

Gennaro Daniele ◽

Francesco Raspagliesi ◽

Giovanni Scambia ◽

Carmela Pisano ◽

Nicoletta Colombo ◽

...

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

Prognostic Factors ◽

Residual Disease ◽

Performance Status ◽

Advanced Ovarian Cancer ◽

Line Treatment ◽

First Line ◽

Primary Surgery ◽

First Line Treatment

ObjectiveTo explore the clinical and biological prognostic factors for advanced ovarian cancer patients receiving first-line treatment with carboplatin, paclitaxel, and bevacizumab.MethodsA multicenter, phase IV, single arm trial was performed. Patients with advanced (FIGO (International Federation of Gynecology and Obstetrics) stage IIIB-IV) or recurrent, previously untreated, ovarian cancer received carboplatin (AUC (area under the curve) 5), paclitaxel (175 mg/m2) plus bevacizumab (15 mg/kg) on day 1 for six 3-weekly cycles followed by bevacizumab single agent (15 mg/kg) until progression or unacceptable toxicity up to a maximum of 22 total cycles. Here we report the final analysis on the role of clinical prognostic factors. The study had 80% power with a two-tailed 0.01 α error to detect a 0.60 hazard ratio with a factor expressed in at least 20% of the population. Both progression-free and overall survival were used as endpoints.ResultsFrom October 2012 to November 2014, 398 eligible patients were treated. After a median follow-up of 32.3 months (IQR 24.1–40.4), median progression-free survival was 20.8 months (95% CI 19.1 to 22.0) and median overall survival was 41.1 months (95% CI 39.1 to 43.5). Clinical factors significantly predicting progression-free and overall survival were performance status, stage, and residual disease after primary surgery. Neither baseline blood pressure/antihypertensive treatment nor the development of hypertension during bevacizumab were prognostic. There were two deaths possibly related to treatment, but no unexpected safety signal was reported.ConclusionsEfficacy and safety of bevacizumab in combination with carboplatin and paclitaxel and as maintenance were comparable to previous data. Hypertension, either at baseline or developed during treatment, was not prognostic. Performance status, stage, and residual disease after primary surgery remain the most important clinical prognostic factors.Trial registration numberEudraCT 2012-003043-29; NCT01706120.

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