AstraZeneca has announced that its PD-L1 inhibitor Imfinzi (durvalumab) showed a ‘sustained and clinically meaningful’ survival benefit for patients with extensive stage cell lung cancer (ES-SCLC).

The CASPIAN phase 3 trial for the monoclonal antibody met its primary survival endpoint in June 2019, but the new analysis confirms that the survival benefit remains for more than three years for patients receiving both Imfinzi and chemotherapy versus chemotherapy alone.

Patients receiving the combination therapy saw a 29% reduction in the risk of death versus chemotherapy alone. An exploratory analysis estimated that 17.6% of patients treated with Imfinzi plus chemotherapy were alive after three years, versus 5.8% of patients treated with chemotherapy alone.

Small cell lung cancer accounts for 15% of all lung cancers and has a poor prognosis. For treatment purposes, clinicians divide SCLC into two stages: limited stage – where the tumour is found only in one lung, and extensive stage – where the tumour has spread to the other lung or other parts of the body.

Currently two-thirds of patients are diagnosed with extensive-stage disease. Prior to the arrival of immunotherapies, only 3% of patients with extensive-stage disease were alive after five years.

Imfinzi in combination with chemotherapy (etoposide and either carboplatin or cisplatin) is approved in the first-line treatment of ES-SCLC in more than 55 countries, including the US, Japan, China and across the EU. It is also widely approved in non-small cell lung cancer (NSCLC) in unresectable, stage 3 disease after CRT and in previously treated patients with advanced bladder cancer.

Biogen’s launch of Aduhelm (aducanumab), the first-ever drug to treat the underlying causes of Alzheimer’s disease, has been far from smooth, with intense criticism of its approval, consternation around its high price and resignations from the advisory committee. The company even requested a narrowing of the indication to reduce the impact on payers’ budgets, after estimates placed the bill for Medicare at $29bn for a single year.

However, for Biogen’s CEO, Michel Vounatsos, the problem seems to be more around communications. “There is clearly too much confusion, misinformation and controversy surrounding our data and the approval process,” he said, admitting the company faced some “near-term challenges” in launching the drug.

He cited three near-term priorities for the company as it seeks to overcome the many hurdles in the way of its drug. They are: to improve understanding of Aduhelm clinical data across the board, to expedite the development of the infrastructure necessary to launch the drug and to seek to clarify the reimbursement pathway.

Attention will inevitably focus on the price of the drug, which Biogen has launched at $56,000 per patient per year when cost watchdog, the Institute for Clinical and Economic Review (ICER), suggested the drug should cost no more than $8,300 per year.

With more than six million Americans living with Alzheimer’s disease, the price tag to the US healthcare system will be substantial, and it seems as though most doctors are waiting for more advice.

High-level results from the PROpel phase 3 trial in first-line metastatic castration-resistant prostate cancer (mCRPC) show that AstraZeneca and Merck/MSD’s Lynparza (olaparib) in combination with abiraterone significantly delayed disease progression.

The data monitoring committee concluded that the trial met the primary endpoint of radiographic progression-free survival (rPFS) versus standard-of-care abiraterone in men who had not received treatment with new hormonal agents or chemotherapy.
The PROpel trial also “showed a trend” towards improved overall survival (OS) but AstraZeneca said the data was “still immature” and the trial will assess OS as a key secondary endpoint.

Prostate cancer is the second-most common cancer in men and five-year survival remains low for men with mCRPC in spite of new treatments.

Lynparza is approved in a number of countries in a range of indications, mostly related to ovarian cancer, although it is also approved for forms of advanced breast and pancreatic cancer in several countries.

The drug is being jointly developed and commercialised by AstraZeneca and Merck/MSD, and has been used to treat over 40,000 patients worldwide. It is also the focus of “the broadest and most advanced clinical trial development programme of any PARP inhibitor”, according to AstraZeneca and Merck.

“These exciting results demonstrate the potential for Lynparza with abiraterone to become a new first-line option for patients regardless of their biomarker status and reach a broad population of patients living with this aggressive disease,” said Susan Galbraith, head of oncology R&D at AstraZeneca.

Novartis has presented a final analysis of its phase 3 MONALEESA-2 trial showing a survival benefit of more than 12 months for its CDK4/6 inhibitor, Kisqali (ribociclib) in combination with letrozole after five years.

The study evaluated Kisqali in combination with letrozole, compared to placebo plus letrozole, in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced or metastatic breast cancer with no prior systemic treatment for advanced disease.

MONALEESA-2 showed that, after five years, patients treated with Kisqali in combination with letrozole had more than a 50% chance of survival. This means Kisqali is the only CDK4/6 inhibitor with proven overall survival benefit across all three phase 3 trials of the MONALEESA programme with different endocrine therapy partners regardless of menopausal status or line of therapy, said Novartis.

The study is part of Novartis’ aim to “reimagine medicine and strive for cures”, said Susanne Schaffert, president of Novartis Oncology. “Our mission is to improve and extend the lives of those with cancer. For people with HR+/HER2- advanced breast cancer, this data is not just numbers and may mean more life milestones.”

Kisqali is approved in the US and EU as initial endocrine-based therapy in combination with an aromatase inhibitor for postmenopausal women with HR+/HER2- locally advanced or metastatic breast cancer and pre-, peri- or postmenopausal women, as well as both first- or second-line therapy in postmenopausal women in combination with fulvestrant.

While screening and prevention programmes have slashed the number of women developing cervical cancer, it remains a leading cause of cancer-related death among women globally. Advanced cervical cancer has also proved extremely difficult to treat.

However, there is good news on the horizon for the 15,000 women diagnosed with the disease each year in the US.

The Food and Drug Administration (FDA) has approved the antibody-drug conjugate Tivdak (tisotumab vedotin-tftv) for recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

Also, two clinical trials involving combination therapies – involving both Tivdak and Merck’s Keytruda – have shown encouraging results.

Tivdak – which was granted priority review by the FDA in April – is an antibody-drug conjugate composed of Genmab’s human monoclonal antibody and Seagen’s ADC technology involving monomethyl auristatin E (MMAE). The ADC is directed to tissue factor, a cell-surface protein expressed on multiple solid tumours associated with tumour growth, angiogenesis and metastasis.

The FDA approval is based on results from a phase 2 trial, innovaTV 204, which evaluated Tivdak as second or third-line treatment in 101 women with recurrent or metastatic cervical cancer, two-thirds of which had previously received Avastin (bevacizumab).

“This is an important development for patients with recurrent or metastatic cervical cancer,” said Robert Coleman, Seagen chief scientific officer, US oncology research and lead investigator of the innovaTV 204 clinical trial.

A global, randomised phase 3 clinical trial (innovaTV 301) is underway and is also intended to support global registrations.