4.6 Review

Overcoming the challenges of drug development in platinum-resistant ovarian cancer

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Article Oncology

Efficacy and Safety of Mirvetuximab Soravtansine in Patients With Platinum-Resistant Ovarian Cancer With High Folate Receptor Alpha Expression: Results From the SORAYA Study

Ursula A. A. Matulonis et al.

Summary: The MIRV antibody-drug conjugate demonstrated significant antitumor activity and favorable tolerability in patients with platinum-resistant epithelial ovarian cancer, particularly in those who had received multiple prior therapies including bevacizumab.

JOURNAL OF CLINICAL ONCOLOGY (2023)

Article Oncology

Safety and efficacy of mirvetuximab soravtansine, a folate receptor alpha (FR?)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients with platinum-resistant ovarian cancer

Lucy Gilbert et al.

Summary: The combination of mirvetuximab soravtansine and bevacizumab demonstrated antitumor activity and safety in patients with platinum-resistant ovarian cancer. The treatment achieved high objective response rate (44%) and prolonged duration of response (median 9.7 months). The study suggests that mirvetuximab soravtansine could be a potential combination partner for bevacizumab in this patient population.

GYNECOLOGIC ONCOLOGY (2023)

Article Oncology

Efficacy and safety of standard of care with/without bevacizumab for platinum-resistant ovarian/fallopian tube/peritoneal cancer previously treated with bevacizumab: The Japanese Gynecologic Oncology Group study JGOG3023

Tadahiro Shoji et al.

Summary: The study confirmed the efficacy and safety of further bevacizumab therapy in patients with platinum-resistant ovarian cancer whose disease had progressed after bevacizumab monotherapy, particularly in extending progression-free survival.

CANCER SCIENCE (2022)

Article Oncology

Randomized phase II trial of weekly paclitaxel vs. cediranib-olaparib (continuous or intermittent schedule) in platinum-resistant high-grade epithelial ovarian cancer

Nicoletta Colombo et al.

Summary: The combination of cediranib and olaparib did not improve the progression-free survival (PFS) compared to chemotherapy in heavily pretreated platinum-resistant ovarian cancer patients. However, this oral doublet is still an effective option for this difficult-to-treat population.

GYNECOLOGIC ONCOLOGY (2022)

Article Oncology

Rucaparib versus standard-of-care chemotherapy in patients with relapsed ovarian cancer and a deleterious BRCA1 or BRCA2 mutation (ARIEL4): an international, open-label, randomised, phase 3 trial

Rebecca Kristeleit et al.

Summary: In patients with BRCA1 or BRCA2 mutated ovarian carcinoma, rucaparib demonstrated better progression-free survival compared to chemotherapy. The results of this study support rucaparib as an alternative treatment option for patients with relapsed BRCA-mutated ovarian carcinoma.

LANCET ONCOLOGY (2022)

Article Oncology

Cediranib in Combination with Olaparib in Patients without a Germline BRCA1/2 Mutation and with Recurrent Platinum-Resistant Ovarian Cancer: Phase IIb CONCERTO Trial

Jung-Min Lee et al.

Summary: The efficacy, safety, and tolerability of cediranib plus olaparib were investigated in patients with platinum-resistant recurrent ovarian cancer. The combination therapy showed some clinical activity in heavily pretreated, non-gBRCAm patients, highlighting the need for further biomarker studies.

CLINICAL CANCER RESEARCH (2022)

Article Oncology

Platinum vs non-platinum chemotherapy for platinum-resistant ovarian cancer: A meta-analysis.

Alexey Rumyantsev et al.

JOURNAL OF CLINICAL ONCOLOGY (2022)

Article Oncology

Challenges for immunotherapy for the treatment of platinum resistant ovarian cancer

Olivia Le Saux et al.

Summary: Platinum resistant ovarian cancer is a heterogeneous disease with poor prognosis and reduced immune cell infiltration, leading to low response rates to anti-PD1/PD-L1 monotherapy. Various therapeutic strategies are being investigated to enhance response rates, including combining chemotherapy, anti-angiogenic agents, and other immune checkpoint inhibitors.

SEMINARS IN CANCER BIOLOGY (2021)

Article Oncology

Combination ATR and PARP Inhibitor (CAPRI): A phase 2 study of ceralasertib plus olaparib in patients with recurrent, platinum-resistant epithelial ovarian cancer

Payal D. Shah et al.

Summary: In platinum-resistant HGSOC patients, the combination therapy of olaparib plus ceralasertib was well-tolerated, with no objective responses observed. However, a signal of activity was seen particularly in diseases associated with BRCA1 mutations. Further evaluation should include alternate dosing strategies in genomically-selected populations.

GYNECOLOGIC ONCOLOGY (2021)

Article Oncology

Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I

K. N. Moore et al.

Summary: The study found that in patients with platinum-resistant EOC, MIRV did not significantly improve PFS compared to chemotherapy. However, MIRV showed superior outcomes in secondary endpoints, particularly in patients with high FR alpha expression, and had a more manageable safety profile compared to chemotherapy.

ANNALS OF ONCOLOGY (2021)

Article Oncology

Revisiting antibody-drug conjugates and their predictive biomarkers in platinum-resistant ovarian cancer

Khalid El Bairi et al.

Summary: Platinum-resistant ovarian cancer poses significant challenges in treatment options, with limited therapeutic choices available for patients. The emergence of antibody-drug conjugates (ADCs) provides promising findings for further clinical development in this setting.

SEMINARS IN CANCER BIOLOGY (2021)

Review Oncology

Ovarian Cancer Treatments Strategy: Focus on PARP Inhibitors and Immune Check Point Inhibitors

Camilla Nero et al.

Summary: Ovarian cancer treatment relies on cytoreductive surgery, platinum-based chemotherapy, and targeted therapies. While PARP inhibitors have shown remarkable results, immunotherapy outcomes have been disappointing. Further research on combining different treatment modalities is warranted.

CANCERS (2021)

Review Oncology

Immune-Checkpoint Inhibitors in Platinum-Resistant Ovarian Cancer

Alice Indini et al.

Summary: Patients with platinum-resistant ovarian cancer have a poor prognosis with limited treatment options. While single-agent immunotherapy has shown disappointing results, combining immunotherapy with target therapies like PARP inhibitors and TKIs appears promising. Ongoing trials are evaluating these combination strategies to assess their impact and cost-effectiveness.

CANCERS (2021)

Review Pharmacology & Pharmacy

Advances in the treatment of platinum resistant epithelial ovarian cancer: an update on standard and experimental therapies

Shuk on Annie Leung et al.

Summary: PROC is defined as disease recurrence within 6 months of completing platinum-based chemotherapy, generally associated with poor outcomes and low response rates. Recent developments in therapeutics based on biomarkers and a more nuanced understanding of DNA repair and immunologic pathways have led to novel treatment options, such as PARP inhibitors, cell cycle checkpoint inhibitors, and immune checkpoint inhibitors.

EXPERT OPINION ON INVESTIGATIONAL DRUGS (2021)

Article Oncology

Lurbinectedin versus pegylated liposomal doxorubicin or topotecan in patients with platinum-resistant ovarian cancer: A multicenter, randomized, controlled, open-label phase 3 study (CORAIL)

Stephanie Gaillard et al.

Summary: The CORAIL trial did not find an improvement in progression-free survival with lurbinectedin compared to standard treatments for platinum-resistant ovarian cancer. However, lurbinectedin showed similar antitumor efficacy and better tolerance compared to current standard of care in this patient population.

GYNECOLOGIC ONCOLOGY (2021)

Article Oncology

Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA)

Junzo Hamanishi et al.

Summary: The study compared the efficacy and safety of nivolumab versus chemotherapy in patients with platinum-resistant ovarian cancer, and found that although nivolumab was well-tolerated, it did not improve overall survival and showed worse progression-free survival compared to chemotherapy.

JOURNAL OF CLINICAL ONCOLOGY (2021)

Article Oncology

Avelumab alone or in combination with chemotherapy versus chemotherapy alone in platinum-resistant or platinum-refractory ovarian cancer (JAVELIN Ovarian 200): an open-label, three-arm, randomised, phase 3 study

Eric Pujade-Lauraine et al.

Summary: This study compared the efficacy of avelumab alone, avelumab plus PLD, and PLD alone in patients with platinum-resistant or platinum-refractory ovarian cancer. The results showed that neither avelumab plus PLD nor avelumab alone significantly improved progression-free survival or overall survival compared to PLD.

LANCET ONCOLOGY (2021)

Article Medicine, General & Internal

Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer

K. Moore et al.

NEW ENGLAND JOURNAL OF MEDICINE (2018)

Review Oncology

Precision medicine becomes reality-tumor type-agnostic therapy

Li Yan et al.

CANCER COMMUNICATIONS (2018)

Editorial Material Oncology

Moving beyond the platinum sensitive/resistant paradigm for patients with recurrent ovarian cancer

Ronald D. Alvarez et al.

GYNECOLOGIC ONCOLOGY (2016)

Article Oncology

Endpoints for assessing drug activity in clinical trials

Richard Pazdur

ONCOLOGIST (2008)

Article Medicine, General & Internal

Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer

Kathy Miller et al.

NEW ENGLAND JOURNAL OF MEDICINE (2007)