Prolonged Disease-Free and Treatment-Free Survival in Platinum-Resistant Ovarian Cancer Following Extended (> 1 Year) Administration of Single-Agent Paclitaxel: A Case Report and Discussion of Potential Clinical Implications

e15544 Background: Platinum resistant-refractory ovarian cancer (PRROC) patients have a poor outcome; single-agent therapy is still the gold standard, with overall response rate lesser than 20% and progression-free-survival is not higher than 4 months. Methods: We tested safety and activity of a two-drugs-regimen containing NPLED and cyclophosphamide in a phase II open label study. From October 2007 to October 2011 thirty-two patients with platinum-resistant/refractory disease were enrolled. Enrolled patients were pretreated with a median number of 2 lines of chemotherapy, ranging from 1 to 5. NPLED and cyclophosphamide were administered at the dose of 60 mg. and 600 mg p.s.m. respectively. Results: Patients received a median number of three cycles of chemotherapy. A total of 145 cycles were administered: as G3 toxicities we registered emesis (6%), diaorrhea (3%), asthenia, and alopecia. No grade 4 adverse events occurred. Among the 30 patients evaluable for response we observed 5 (17%) partial responses and 10 (33%) stable diseases. The median progression-free-survival was 13 weeks and the median survival was 46 weeks. Conclusions: These results are similar to other data reported in literature. In conclusion we may affirm that the association of NPLED and cyclophosphamide is active and safe when administered in PRROC, but it don’t modify the prognosis of this subset of patients.

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Randomized phase II CLIO study on olaparib monotherapy versus chemotherapy in platinum-resistant ovarian cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.5507 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 5507-5507 ◽

Cited By ~ 5

Author(s):

Adriaan Vanderstichele ◽

Els Van Nieuwenhuysen ◽

Sileny Han ◽

Nicole Concin ◽

Toon Van Gorp ◽

...

Keyword(s):

Ovarian Cancer ◽

Single Agent ◽

Progression Free Survival ◽

Standard Of Care ◽

Free Survival ◽

Clinical Endpoints ◽

Platinum Resistant ◽

Randomized Phase Ii ◽

Duration Of Response ◽

Grade 3

5507 Background: The CLIO trial (NCT02822157) evaluated olaparib single-agent therapy versus standard of care chemotherapy in platinum-resistant (recurrence within 6 months after last platin) ovarian cancer (PROC). Methods: Eligible patients with measurable disease and ≥1 prior line of chemotherapy were randomized 2:1 to Olaparib (OLA) monotherapy (300 mg tablets, BID) or physician’s choice chemotherapy (CT; PLD 40 mg/m2 q 4 wks; Topotecan 1.25 mg/m2 day 1—5 q 3 wks; Paclitaxel 80 mg/m2 day 1, 8,15 q 3 wks; Gemcitabine 1000 mg/m2 day 1, 8 and 15 q 4 wks). Primary endpoint was objective overall response (ORR) per RECIST v1.1. Germline BRCA status was available for all patients. Disease control rate (DCR) was defined as response for at least 12 wks. Results: 100 patients with PROC were randomized 2:1 to OLA (N = 67) or CT (N = 33). Median prior lines of treatment was 3 (range: 1—8). ORR (unconfirmed) was 18% (12/67) for OLA and 6% (2/33) for CT. ORR for OLA was 38% (5/13) in gBRCAm and 13% (7/54) in gBRCAwt patients. Of note, 2 patients with gBRIP1 mutation had no response under OLA. DCR was 35.8% (24/67) for OLA and 42% (14/33) for CT. DCR under OLA in gBRCAm was 62% (8/13) compared to 30% (16/54) in gBRCAwt disease. The median duration of response (DOR) and the median progression-free survival (PFS) was similar: 5.4 months vs 4.5 months (DOR) and 2.9 vs 3.4 months (PFS) for OLA and CT, respectively. Grade ≥3 treatment-related AEs occurred in 60% vs 52% for OLA and CT, respectively. Somatic HRR mutation analysis is ongoing and will be presented. Conclusions: Olaparib monotherapy showed a favorable response rate in PROC compared with chemotherapy also in gBRCAwt patients. Analysis of clinical endpoints in relation to HRR is ongoing and will be presented. Clinical trial information: NCT02822157.

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A randomized trial comparing single-agent carboplatin with carboplatin followed by radiotherapy for advanced ovarian cancer: a North Thames Ovary Group study.

Journal of Clinical Oncology ◽

10.1200/jco.1993.11.3.440 ◽

1993 ◽

Vol 11 (3) ◽

pp. 440-448 ◽

Cited By ~ 58

Author(s):

H E Lambert ◽

G J Rustin ◽

W M Gregory ◽

A E Nelstrop

Keyword(s):

Ovarian Cancer ◽

Randomized Trial ◽

Residual Disease ◽

Single Agent ◽

Disease Free Survival ◽

Outpatient Basis ◽

Consolidation Therapy ◽

Free Survival ◽

Second Look ◽

Disease Free

PURPOSE To determine in a randomized trial of advanced ovarian carcinoma whether consolidation therapy with whole-abdominal radiotherapy (RT) after chemotherapy improves survival and disease-free survival compared with the continued chemotherapy. PATIENTS AND METHODS Two hundred fifty-four patients with advanced epithelial ovarian cancer (stages IIB to IV) were entered onto a study of five monthly courses of 400 mg/m2 of carboplatin. One hundred seventeen patients with residual disease of 2 cm or less at second-look laparotomy or laparoscopy were then randomized to receive consolidation therapy, either five further courses of carboplatin at the same dosage or whole-abdominal RT (24 Gy). There was no control arm. RESULTS Chemotherapy was well tolerated and was usually administered on an outpatient basis. Myelosuppression that was sufficient to delay chemotherapy occurred in only 3% of 1,418 courses analyzed. The main toxicity of carboplatin was nausea and vomiting, but this was easier to control than that with cisplatin. Although RT was well tolerated in the majority of the 58 patients, one patient who had been found to have multiple adhesions at second-look surgery developed fecal fistulae post-RT that resulted in the patient's death from peritonitis. Median survival for the whole group from date of surgery was 25 months. No statistical difference was found in either survival or disease-free survival between those patients who received consolidation chemotherapy and those who were treated with abdominal RT. Prognostic factors used to assess survival were stage, histology, amount of residual disease after primary surgery, and presence of tumor at second-look surgery. CONCLUSION There seems to be no significant advantage for consolidation whole-abdominal RT compared with the continuation of the same chemotherapy in the management of advanced epithelial carcinoma of the ovary, even when no macroscopic residual disease is apparent at second-look surgery.

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Randomized Phase III Trial of Gemcitabine Compared With Pegylated Liposomal Doxorubicin in Patients With Platinum-Resistant Ovarian Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.09.6735 ◽

2007 ◽

Vol 25 (19) ◽

pp. 2811-2818 ◽

Cited By ~ 243

Author(s):

David G. Mutch ◽

Mauro Orlando ◽

Tiana Goss ◽

Michael G. Teneriello ◽

Alan N. Gordon ◽

...

Keyword(s):

Ovarian Cancer ◽

Liposomal Doxorubicin ◽

Single Agent ◽

Pegylated Liposomal Doxorubicin ◽

Progression Free Survival ◽

Therapeutic Index ◽

Phase Iii ◽

End Points ◽

Platinum Resistant ◽

Significant Difference

Purpose Ovarian cancer (OC) patients experiencing progressive disease (PD) within 6 months of platinum-based therapy in the primary setting are considered platinum resistant (Pt-R). Currently, pegylated liposomal doxorubicin (PLD) is a standard of care for treatment of recurrent Pt-R disease. On the basis of promising phase II results, gemcitabine was compared with PLD for efficacy and safety in taxane-pretreated Pt-R OC patients. Patients and Methods Patients (n = 195) with Pt-R OC were randomly assigned to either gemcitabine 1,000 mg/m2 (days 1 and 8; every 21 days) or PLD 50 mg/m2 (day 1; every 28 days) until PD or undue toxicity. Optional cross-over therapy was allowed at PD or at withdrawal because of toxicity. Primary end point was progression-free survival (PFS). Additional end points included tumor response, time to treatment failure, survival, and quality of life. Results In the gemcitabine and PLD groups, median PFS was 3.6 v 3.1 months; median overall survival was 12.7 v 13.5 months; overall response rate (ORR) was 6.1% v 8.3%; and in the subset of patients with measurable disease, ORR was 9.2% v 11.7%, respectively. None of the efficacy end points showed a statistically significant difference between treatment groups. The PLD group experienced significantly more hand-foot syndrome and mucositis; the gemcitabine group experienced significantly more constipation, nausea/vomiting, fatigue, and neutropenia but not febrile neutropenia. Conclusion Although this was not designed as an equivalency study, gemcitabine and PLD seem to have a comparable therapeutic index in this population of Pt-R taxane-pretreated OC patients. Single-agent gemcitabine may be an acceptable alternative to PLD for patients with Pt-R OC.

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Adding bevacizumab to single-agent chemotherapy for the treatment of platinum-resistant recurrent ovarian cancer: A cost-effectiveness analysis of the AURELIA trial

Gynecologic Oncology ◽

10.1016/j.ygyno.2016.04.116 ◽

2016 ◽

Vol 141 ◽

pp. 36

Author(s):

W.Z. Wysham ◽

E.M. Schaffer ◽

T.M. Coles ◽

D.R. Roque ◽

S.B. Wheeler ◽

...

Keyword(s):

Ovarian Cancer ◽

Cost Effectiveness ◽

Single Agent ◽

Recurrent Ovarian Cancer ◽

Cost Effectiveness Analysis ◽

Effectiveness Analysis ◽

Platinum Resistant ◽

Single Agent Chemotherapy

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A phase II study of single-agent RO4929097, a gamma-secretase inhibitor of Notch signaling, in patients with recurrent platinum-resistant epithelial ovarian cancer: A study of the Princess Margaret, Chicago and California phase II consortia

Gynecologic Oncology ◽

10.1016/j.ygyno.2015.03.005 ◽

2015 ◽

Vol 137 (2) ◽

pp. 216-222 ◽

Cited By ~ 32

Author(s):

Ivan Diaz-Padilla ◽

Michelle K. Wilson ◽

Blaise A. Clarke ◽

Hal W. Hirte ◽

Stephen A. Welch ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Notch Signaling ◽

Phase Ii ◽

Phase Ii Study ◽

Single Agent ◽

Gamma Secretase ◽

Platinum Resistant ◽

Secretase Inhibitor ◽

Gamma Secretase Inhibitor

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Is FDA-Approved Bevacizumab Cost-Effective When Included in the Treatment of Platinum-Resistant Recurrent Ovarian Cancer?

Journal of Oncology Practice ◽

10.1200/jop.2015.010470 ◽

2016 ◽

Vol 12 (7) ◽

pp. e775-e783 ◽

Cited By ~ 3

Author(s):

Nicole P. Chappell ◽

Caela R. Miller ◽

Aaron D. Fielden ◽

Jason C. Barnett

Keyword(s):

Ovarian Cancer ◽

Cost Effectiveness ◽

Willingness To Pay ◽

Progression Free Survival ◽

Recurrent Ovarian Cancer ◽

Phase Iii ◽

Value Assessment ◽

Free Survival ◽

Platinum Resistant ◽

The Cost

Purpose: Although the Food and Drug Administration has approved incorporation of bevacizumab (BEV) into the treatment of platinum-resistant ovarian cancer (PROC), cost-value measures are an essential consideration, as evidenced by the recent ASCO Value Framework initiative. We assessed the cost-effectiveness and reviewed the net health benefit (NHB) of this expensive treatment. Methods: A cost-effectiveness decision model was constructed using results from a phase III trial comparing BEV plus cytotoxic chemotherapy with chemotherapy alone in patients with PROC. The Avastin Use in Platinum-Resistant Epithelial Ovarian Cancer (AURELIA) trial demonstrated improvement in progression-free survival and quality of life in patients receiving BEV. Costs, paracentesis rates, and adverse events were incorporated, including subgroup analysis of different partner chemotherapy agents. Results: Inclusion of BEV in the treatment of platinum-resistant recurrent ovarian cancer meets the common willingness-to-pay incremental cost-effectiveness ratio (ICER) threshold of $100,000 per progression-free life-year saved (LYS) for 15-mg/kg dosing and approaches this threshold for 10-mg/kg dosing, with an ICER of $160,000. In sensitivity analysis, reducing the cost of BEV by 13% (from $9,338 to $8,100 per cycle) allows 10-mg/kg dosing to reach a $100,000 ICER. Exploratory analysis of different BEV chemotherapy partners showed an ICER of $76,000 per progression-free LYS (6.5-month progression-free survival improvement) and $54,000 per LYS (9.1-month overall survival improvement) for the addition of BEV to paclitaxel once per week. Using the ASCO framework for value assessment, the NHB score for BEV plus paclitaxel once per week is 48. Conclusion: Using a willingness-to-pay threshold of $100,000 ICER, the addition of BEV to chemotherapy either demonstrates or approaches cost-effectiveness and NHB when added to the treatment of patients with PROC.

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Increased circulating tumor DNA as a noninvasive biomarker of early treatment response in patients with metastatic ovarian carcinoma: A pilot study

Tumor Biology ◽

10.1177/1010428320919198 ◽

2020 ◽

Vol 42 (5) ◽

pp. 101042832091919 ◽

Cited By ~ 1

Author(s):

Mariana Cartaxo Alves ◽

Fernando Luiz Affonso Fonseca ◽

Alayne Magalhães Trindade Domingues Yamada ◽

Lílian Arruda do Rego Barros ◽

André Lopes ◽

...

Keyword(s):

Ovarian Cancer ◽

Ovarian Carcinoma ◽

Systemic Treatment ◽

Disease Free Survival ◽

Advanced Ovarian Cancer ◽

Early Response ◽

Circulating Tumor Dna ◽

Free Survival ◽

Disease Free ◽

Tumor Dna

Detection of circulating tumor DNA is a new noninvasive technique with potential roles in diagnostic, follow-up, and prognostic evaluation of patients with many types of solid tumors. We aimed to evaluate the role of circulating tumor DNA in the setting of metastatic ovarian carcinoma. A prospective cohort of patients with metastatic ovarian cancer who were referred to systemic therapy was enrolled. Blood samples were collected before the start of treatment and monthly thereafter for 6 months. Circulating tumor DNA was quantified by real-time quantitative reverse transcription polymerase chain reaction of different lengths of Arthrobacter luteus elements as described by Umetani et al. A total of 11 patients were included, 2 for primary disease and 9 for recurrent disease. After the first cycle of chemotherapy, patients whose circulating tumor DNA levels increased from baseline were more likely to respond to chemotherapy than those whose circulating tumor DNA levels did not increase (p = 0.035). Furthermore, patients whose circulating tumor DNA levels rose after the first cycle of chemotherapy also had improved disease-free survival compared to those whose circulating tumor DNA levels did not increase (p = 0.0074). We conclude that the increase in circulating tumor DNA values collected in peripheral blood after the first cycle of systemic treatment in patients with advanced ovarian cancer is associated with an early response to systemic treatment and correlates with superior disease-free survival in this population. Circulating tumor DNA might be a specific, noninvasive, and cost-effective new biomarker of early response to systemic treatment in these patients.

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