Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial

Gallo, Ciro; Colombo, Nicoletta; Bamias, Aristotelis; Salutari, Vanda; Frezzini, Simona; Pautier, Patricia; Orditura, Michele; Dubot, Coraline; Ray‐Coquard, Isabelle; Scambia, Giovanni; Pignata, Sandro; Lorusso, Domenica; Joly, Florence; Sessa, Cristiana; Selle, Frédèric; Giorgi, Ugo De; Bologna, Alessandra; Gadducci, Angiolo; Mammoliti, Serafina; Ray-Coquard, I. L.; Zafarana, Elena; Breda, Enrico; Favier, Laure; Ardizzoia, Antonio; Cinieri, Saverio; Largillier, R.; Sambataro, Daniela; Guardiola, Emmanuel; Lauria, Rossella; Pisano, Carmela; Raspagliesi, Francesco; Daniele, Gennaro; Perrone, Francesco

doi:10.1016/s1470-2045(20)30637-9

Cited by 97 publications

(95 citation statements)

References 15 publications

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“…Consequently, we defined a threshold of 75% completion rate to be an indicator of the desensitization protocol’s effectiveness. Furthermore, the expectation rate in previous studies ranged between 90 and 100% [ 6 – 12 ]; thus, we established an expectation of 95% completion rate. We planned for 80% power and an α error of 5%, and we assumed a sample size of 20 participants.…”

Section: Methodsmentioning

confidence: 60%

“…Platinum-sensitive ovarian cancer is defined as a platinum-free interval of 6 months or longer. Treatment for platinum-sensitive recurrent ovarian cancer typically includes a carboplatin-containing regimen, such as carboplatin plus paclitaxel, gemcitabine, pegylated liposomal doxorubicin [ 1 – 3 ], and carboplatin plus paclitaxel or gemcitabine or pegylated liposomal doxorubicin with bevacizumab [ 4 – 6 ]. The median survival time of carboplatin rechallenge in patients with platinum-sensitive recurrent ovarian cancer is approximately 30 months.…”

Section: Introductionmentioning

confidence: 99%

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4-step, 2-h carboplatin desensitization in Japanese patients with ovarian cancer: a prospective study

et al. 2021

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Background Carboplatin is a key drug for ovarian cancer. However, it sometimes induces hypersensitivity reactions (HSRs) that result in the discontinuation of the treatment. Although various desensitization protocols have been reported in previous retrospective studies, a limited number of prospective studies have analyzed these protocols. Methods Patients with platinum-sensitive relapsed ovarian cancer who experienced carboplatin-induced HSRs were treated with diluted solutions of 1/1000, 1/100, 1/10 and an undiluted solution of carboplatin over a 1-h period. If no HSRs occurred within the first two cycles, a short protocol regimen over a 30-min period per solution was followed. The primary endpoint was treatment completion rate. Results Between May 2015 and September 2018, 21 patients were enrolled from two institutions. One patient experienced platinum-sensitive recurrence after the desensitization protocol; thus, 22 sessions were analyzed. Epinephrine use, treatment-related death, and intensive care unit (ICU) admissions did not occur. The median number of desensitization cycles was 6 (range 1–6). Two sessions were discontinued early because of grade 2 dysgeusia and grade 2 malaise. Treatment in two (9.1%) patients was discontinued because of HSR development. The treatment completion rate was 90.9%. Six (27.3%) sessions met the criteria for transition to the short protocol regimen. In 14 (63.6%) sessions, HSRs were observed during infusion of the undiluted solution. The median progression-free survival and overall survival were 14.8 and 23.8 months, respectively. Conclusion This 4-step, 2-h carboplatin desensitization protocol is safe and feasible. Patients require careful monitoring with a rapid response to HSRs, especially during the administration of undiluted solutions.

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Section: Methodsmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 99%

4-step, 2-h carboplatin desensitization in Japanese patients with ovarian cancer: a prospective study

et al. 2021

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“…The remaining three trials with significant results investigated carboplatin doublet chemotherapy plus bevacizumab (versus carboplatin doublet chemotherapy), carboplatin plus gemcitabine (versus carboplatin monotherapy) and carboplatin plus PLD plus bevacizumab (versus carboplatin/gemcitabine/bevacizumab), which all showed an improved PFS over the comparator, but did not result in OS benefit and showed no improved QoL. 10 , 11 , 12 This qualifies as only limited clinical benefit with ESMO-MCBS grades of 3, 2 and 1, respectively. An overview of the relative benefit between the different arms and comparators studied and graded for the platinum-sensitive setting is provided in Figure 2 A.…”

Section: Resultsmentioning

confidence: 99%

Clinical benefit of systemic therapies for recurrent ovarian cancer—ESMO-MCBS scores

et al. 2021

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Background Licensed systemic treatment options for platinum-sensitive recurrent ovarian cancer are platinum-based chemotherapy and maintenance treatment with bevacizumab and poly (ADP-ribose) polymerase inhibitors. For platinum-resistant disease, several non-platinum options are available. We aimed to assess the clinical benefit of these treatments according to the European Society of Medical Oncology (ESMO)-Magnitude of Clinical Benefit Scale (MCBS). Materials and methods A PubMed search was carried out including all studies evaluating systemic treatment of recurrent epithelial ovarian cancer, from 1990 onwards. Randomised trials with an adequate comparator and design showing a statistically significant benefit of the study arm were independently scored by two blinded observers using the ESMO-MCBS. Results A total of 1127 papers were identified, out of which 61 reported results of randomised trials of sufficient quality. Nineteen trials showed statistically significant results and the studied treatments were graded according to ESMO-MCBS. Only three treatments showed substantial benefit (score of 4 on a scale of 1-5) according to the ESMO-MCBS: platinum-based chemotherapy with paclitaxel in the platinum-sensitive setting and the addition of bevacizumab to chemotherapy in the platinum-resistant setting. The WEE1 inhibitor adavosertib (not licensed) also scores a 4, based on a recent small phase II study. Assessment of quality-of-life data and toxicity using the ESMO-MCBS showed to be complex, which should be taken into account in using this score for clinical decision making. Conclusion Only a few licensed systemic therapies for recurrent ovarian cancer show substantial clinical benefit based on ESMO-MCBS scores. Trials demonstrating overall survival benefit are sparse.

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“…In addition, the data were obtained from the majority of the patients, in contrast to randomized clinical trials in which many patients are excluded due to the stringent exclusion criteria. Although it has been suggested that platinum sensitivity should not be classified based on a six-month cut-off from the last platinum-based chemotherapy, and other factors such as tumor biology, tumor histology, prior response, persistent toxicity, symptoms, and patients’ preferences should be taken into account together for the choice of chemotherapeutic regimens [ 7 ], currently several clinical trials still implement the concept of platinum-free interval, because it is a more feasible way to categorize patients for their research purposes [ 8 , 9 , 10 ]. The strength of our study is that, in contrast to multiple studies of platinum-sensitive recurrence ovarian cancer that did not report or had immature OS data ( Table 2 ) [ 7 , 8 , 10 , 36 , 37 , 38 ], it provided the overall survival data of these patients.…”

Section: Discussionmentioning

confidence: 99%

“…The Fifth Ovarian Cancer Consensus suggested that the specific time from last platinum should be reported to avoid arbitrary division of platinum-sensitive (PS) or platinum-resistant (PR) patients [ 7 ]. However, for research purposes, the current clinical trials still utilize the classic classification [ 8 , 9 , 10 ]. If the TFIp is >6 months, the patients are deemed PS; within this group, patients with a TFIp between 6 and 12 months are considered partially PS and patients with a TFIp longer than 12 months are considered complete PS.…”

Section: Introductionmentioning

confidence: 99%

Chemotherapeutic Regimens and Chemotherapy-Free Intervals Influence the Survival of Patients with Recurrent Advanced Epithelial Ovarian Carcinoma: A Retrospective Population-Based Study

Huang

Chiang

Chen

et al. 2021

IJERPH

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We aimed to evaluate factors influencing the outcomes of patients with platinum-sensitive recurrent epithelial ovarian carcinoma (EOC). Patients with advanced-stage EOC, who received debulking surgery and adjuvant chemotherapy for recurrence, were obtained from the National Health Insurance Research database of Taiwan between 2000 and 2013. A total of 1038 patients with recurrent advanced-stage EOC were recruited. The platinum + paclitaxel (PT) group had the best five-year overall survival (OS) compared with the other three groups (p < 0.001). The hazard ratios (HRs) of five-year OS for the platinum + liposomal doxorubicin (PD), topotecan (TOP), and pegylated liposomal doxorubicin (PLD) groups were 1.21 (p = 0.07), 1.35 (p = 0.016), and 1.80 (p < 0.001), respectively, compared with the PT group. The PT group also had lower hazard ratios of five-year OS for patients with platinum therapy-free interval (TFIp) between 6 and 12 months compared with the other three groups (p < 0.0001). However, the HRs of five-year OS did not differ between the PT and PD groups in patients with TFIp >12 months. Patients with TFIp >12 months had lower HRs of five-year OS compared with those with TFIp of 6–12 months, regardless of whether they were treated with platinum-based (p = 0.001) or non-platinum-based (p = 0.003) regimens. Chemotherapeutic regimens and TFIp influenced the outcomes of patients with recurrent EOC. For patients with TFIp of 6–12 months, the PT regimen is the first choice based on their best overall survival result. For patients with TFIp >12 months, either platinum-based or non-platinum regimens could be used because of their similar excellent overall survival.

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Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial

Cited by 97 publications

References 15 publications

4-step, 2-h carboplatin desensitization in Japanese patients with ovarian cancer: a prospective study

4-step, 2-h carboplatin desensitization in Japanese patients with ovarian cancer: a prospective study

Clinical benefit of systemic therapies for recurrent ovarian cancer—ESMO-MCBS scores

Chemotherapeutic Regimens and Chemotherapy-Free Intervals Influence the Survival of Patients with Recurrent Advanced Epithelial Ovarian Carcinoma: A Retrospective Population-Based Study

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