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Ovarian Cancer: Who is on the Cruise to Cure it?

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In this ‘Ovarian Cancer Awareness Month‘ let’s reinforce our idea about the prevalence of ovarian cancer and check out the current efforts being made by the pharmaceutical companies to keep ovarian cancer on a tight leash.

Ovarian cancer is the formation of malignant or cancerous cells in the ovary with the ability to spread to the other parts of the body. 

In woman, normal ovary consists of three major types of cell viz. germ cells, endocrine and interstitial cells, and epithelial cells. In case of ovarian cancer, benign or malignant tumor develops in any of these three ovarian cell types. However, ovarian epithelial carcinoma (aka surface epithelial-stromal tumour) developing in the epithelial cells of ovary is the most common one representing 90% of all the types.

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Figure 1. FIGO stages of ovarian cancer

Incidence_of_ovarian_cancers_by_histopathologyNational Cancer Institute (NCI), 21,290 new cases of ovarian cancer were diagnosed with total deaths of 14,180 women. Initial symptoms of ovarian cancer are difficult to recognize as they are often misdiagnosed as some of the regular stomach problem. These symptoms include bloating, abdominal or pelvic pain, irregular menstruation or vaginal bleeding in women who had menopause, pain and bleeding during sex and other more general symptoms like loss of appetite, fatigue, diarrhea, constipation, nausea etc.

Existing forms of treatment for ovarian cancer are; surgery (almost the inevitable one), chemotherapy (explicitly utilized), hormonal therapy (not a very good option for ovarian cancer), radiation Therapy (overpowered by chemotherapy) and immunotherapy (extensive industry research area).

figure caption            Who is doing what to cure it?

At present more than 349 companies and their partners are busy in developing 422 drugs targeting ovarian cancer. So let us take a look at those pharmaceutical industries in the field of ovarian cancer treatment who have been able to put their candidate product in the front row and evaluate where they are directed to reshape and evolve the ovarian cancer treatment in the future. Coincidentally, all these molecules  belong to immunotherapy treatment class.

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astrazeneca-logoAstraZenecas olaparibpoly ADP-ribose polymerase (PARP) inhibitors in 2015 got approval of National Institute for Health and Care Excellence (NICE) as a targeted ovarian cancer treatment for women who have already received three or more rounds of chemotherapy.

Earlier in 2014 FDA had approved olaparib as a monotherapy for treatment of germline BRCA mutated advanced ovarian cancer treatment after going through three or more rounds of chemotherapy.

Astrazeneca’s cediranib oral  inhibitir of vascular endothelial growth factor (VEGF 1-3) has demonstrated positive results in Phase III trial in combination with platinum-based chemotherapy meaningful in progression-free survival in women with recurrent platinum-sensitive ovarian cancer

Roche’s avastin (bevacizumab) recombinant humanized monoclonal antibody in combination with chemotherapy got  approved by U.S. FDA in 2014 for treatment of platinum-resistant , recurrent ovarian cancer. 

Zeltia’s PM-1183 developed by its unit Pharma Mar was positively recommended by 

Independent Data Monitoring Committee (IDMC) to continue the Phase III clinical trial of PM-1183 on platinum-resistant ovarian cancer patients.

Boehringer Ingelheim’s nintedanib along with carboplatin/paclitaxel  notably delayed the progression of advanced ovarian cancer and showed improvement in PFS in first line treatment of ovarian cancer in its Phase III trial.

GlaxosmithKline’s  pazopanib in Phase III trial shown  some beneficial  results in progression free survival (PFS) after surgery and systemic therapy in advanced ovarian cancer patients.

In 2013 farletuzumab, an investigational humanized monoclonal antibody (mAb) of Morphotek, an Eisai Inc subsidiary failed Phase III clinical trial investigated in combination with carboplatin and a taxane for treatment of patients with relapsed platinum-sensitive epithelial ovarian cancer. In 2015, they have started investigation on farletuzumab as radioimmunotherapy in ovarian cancer treatment.

In Phase I study on adoptive T-cell therapy by Perelman School of Medicine at the University of Pennsylvania School of Medicine, T-cells of the patients activated by dendritic cell vaccine prepared from the tumor cell of the patients were utilized to evoke the patient’s immune system against the cancer cells in advanced ovarian cancer patients.

Various other drugs either in combination or as a single agent are also trying their luck in ovarian cancer treatment market. The companies enter into collaboration to increase the efficiency or to prevent the failure of their candidate drugs

Mammaglobin B (SCGB2A1) has been identified as a novel ovarian tumor rejection antigen by the researchers of Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine.

ImmunoGen’s mirvetuximab soravtansine (IMGN853), a folate receptor-α (FRα)-targeting antibody-drug conjugate combined with  Mercks anti-PD-1 therapy, Keytruda® (pembrolizumab) to be evaluated for patients with platinum resistant ovarian cancer. IMGN853 has already shown positive results as single agent for FRα-positive ovarian cancer. Merck’s vintafolide aimed for the treatment of platinum resistant ovarian cancer failed to push their ovarian cancer ambition as its late stage clinical trial failed.

AstraZeneca’s durvalumab, an anti-PD-L1 checkpoint inhibitor and tremelimumab a CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) checkpoint inhibitor are also in their earlier phases of clinical trial .

Bristol-Myers Squibb nivolumab– a human IgG4 anti-PD-1 monoclonal antibody is also in earlier phases of clinical trial.

 

Off note, many molecules are in late Phase II, which we did not cover in this report and we encourage the readers to visit this website for further information about these molecules.

 

Figure 1 credit: Diagram showing stage 1 ovarian cancer. Cancer Research UK / Wikimedia Commons

Figure 2 credit: Incidence of ovarian cancers by histopathology, 2012.  © Häggström, Mikael.

Featured image credit: Graphics remixed by Medgenera. Female Uterus Abstract Design © guniita (Stock Photo ID: 84230393) 

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