Progress in ovarian cancer reported at ASCO

For years, ovarian cancer has played second fiddle to breast cancer in terms of new therapies, but new trials reported at ASCO suggest the science is starting to catch up.

Encouraging data on the PD1 inhibitor class of immuno-oncology drugs, a new PARP inhibitor, and an antibody-drug conjugate (ADC) from ImmunoGen suggest new drugs are coming through development that will improve therapy, particularly for relapsed ovarian cancer.

One of the main problems with ovarian cancer is that it is often diagnosed late, after it has spread, with the disease particularly hard to treat once it has progressed beyond stage I. More than three quarters of patients have recurrent or progressive disease, and options for those who relapse after first-line chemotherapy have been limited.

That has started to change, however, with Roche’s Avastin (bevacizumab) approved for platinum-resistant, recurrent ovarian cancer last year in the EU, having been approved for platinum-sensitive patients in 2012.

Even more significant was the approval towards the end of last year of AstraZeneca’s Lynparza (olaparib), the first PARP inhibitor to reach the market.

Lynparza was the first drug to be approved for the maintenance treatment of platinum-sensitive relapsed BRCA-mutated epithelial ovarian cancer although a recent decision by the UK’s National Institute for Health and Care Excellence (NICE) not to back its use under the NHS has dashed the hopes of many ovarian cancer patients.

The preliminary guidance came on the back of rejections for Eli Lilly’s Gemzar (gemcitabine) and GlaxoSmithKline’s Hycamtin (topotecan), both of which are available generically, as well as PharmaMar’s Yondelis (trabectedin) in ovarian cancer.

ASCO saw phase II data presented on another PARP inhibitor – Clovis Oncology’s rupacarib – that reinforce the value of the class in ovarian cancer.

Two studies in BRCA-positive patients showed improvements in progression-free survival (PFS) as well as overall response rates in the region of 80 per cent or more that seem to justify the FDA’s recent decision to award the drug breakthrough status.

ImmunoGen’s ADC candidate mirvetuximab soravtansine (IMGN853) achieved impressive results in a trial of 22 patients with a particularly hard-to-treat form of ovarian cancer who had already received multiple prior therapies.

At ASCO, it was reported that among 17 evaluable patients the drug achieved an overall response rate (ORR) of 53 per cent, including one complete response and eight partial responses. The results suggest ImmunoGen may have another ADC winner on its hands, having collaborated with Roche on the development of breast cancer therapy Kadcyla (trastuzumab emtansine).

Meanwhile, it is encouraging for ovarian cancer patients and their oncologists that Merck KGaA and partner Pfizer have selected ovarian cancer as one of the first indications for their checkpoint inhibitor avelumab.

The two companies reported the results of a 75-patient phase Ib study at ASCO that revealed the PD-L1 inhibitor had an overall response rate of nearly 55 per cent, with a median response rotation of 21 weeks.

Rival checkpoint inhibitor Keytruda (pembrolizumab) from Merck & Co (known as MSD outside the US) also showed early promise in recurrent ovarian cancer patients who tested positive for PD-L1, a cancer-related biomarker.

Keytruda achieved an overall response rate of 11.5 per cent out of 26 evaluable patients, including one compete response and two partial responses.

The hope is that these cancer immunotherapies will show much better activity when used in less advanced disease and potentially in combination with drugs with other mechanisms.

Ovarian cancer is the fifth most common cancer among women in the UK, and only 35 per cent of adults diagnosed with the disease in England and Wales are predicted to survive for 10 years.

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