AstraZeneca upbeat on latest Tagrisso and Lynparza results

AstraZeneca released overall survival results from the phase 3 ‘FLAURA’ trial of Tagrisso (osimertinib) in the first-line treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) on Monday.

The FTSE 100 pharmaceuticals giant also released, along with its partner MSD, detailed positive results from the phase 3 ‘PAOLA-1’ trial, which showed Lynparza (olaparib) as demonstrating a “statistically-significant and clinically-meaningful” improvement in progression-free survival (PFS) in women with newly-diagnosed advanced ovarian cancer.

In the FLAURA trial of Tagrisson, the firm said the results showed a “statistically-significant and clinically-meaningful” improvement in overall survival, which it said was a key secondary endpoint for Tagrisso versus gefitinib or erlotinib, both of which were previous standard-of-care treatments in that setting.

Tagrisso delivered a median overall survival of 38.6 months, versus to 31.8 months for the comparator arm.

At three years, 28% of patients in the Tagrisso arm and 9% of patients in the comparator arm remained on first-line study treatment.

Tagrisso also showed a statistically-significant and clinically-meaningful 52% reduction in the risk of central nervous system disease progression, increasing the time patients with central nervous system metastases lived without nervous system disease progression or death.

The results were presented at the Presidential Symposium of the European Society for Medical Oncology (ESMO) 2019 Congress in Barcelona.

“Tagrisso has set a new benchmark in EGFR-mutated non-small cell lung cancer by demonstrating a median overall survival of more than three years,” said AstraZeneca’s executive vice-president of oncology research and development José Baselga.

“We have not before seen survival benefits of this magnitude in any global phase 3 trial with any such therapy.

“The ground-breaking data reaffirm the benefit of using Tagrisso first and further support its use as the first-line standard of care in this setting.”

Dr Suresh Ramalingam, principal investigator of the FLAURA trial from Winship Cancer Institute of Emory University in Atlanta, added that the results of the trial provided further evidence to support the role of osimertinib as the preferred first-line therapy option for patients with EGFR-mutated non-small cell lung cancer.

“It is highly noteworthy that 28% of patients are still being treated with first-line osimertinib at three years, versus 9% on either gefitinib or erlotinib.”

On the PAOLA-1 trial, AstraZeneca and MSD said the trial compared Lynparza when added to standard-of-care bevacizumab, compared to bevacizumab alone, in women in the first-line maintenance setting, irrespective of their genetic biomarker status or outcome from previous surgery.

Investigator-assessed results showed Lynparza added to bevacizumab reduced the risk of disease progression or death by 41%, and improved progression-free survival to a median of 22.1 months, compared to 16.6 months for those treated with bevacizumab alone.

At two years since trial initiation, 46% of women treated with Lynparza added to bevacizumab showed no disease progression, versus 28% of women receiving bevacizumab alone.

The company said the sensitivity analysis of blinded independent central review of progression-free survival was consistent, showing a similar improvement with a median of 26.1 months for Lynparza added to bevacizumab, versus 18.3 months for bevacizumab alone.

It said the safety and tolerability profile of Lynparza and bevacizumab were consistent with those known from previous trials for each medicine, and with no detriment to quality of life.

Those results were also presented during the Presidential Symposium of the 2019 ESMO congress in Barcelona.

AstraZeneca said the trial also included exploratory sub-group analyses, including BRCA-mutated (BRCAm) and broader homologous recombination deficiency (HRD) populations, which showed treatment with Lynparza added to bevacizumab demonstrated greater benefit compared to bevacizumab alone.

In the BRCAm-positive sub-group, Lynparza added to bevacizumab reduced the risk of disease progression or death by 69%, and in the broader HRD-positive sub-group, which represented approximately half of women with newly-diagnosed advanced ovarian cancer and included BRCAm, Lynparza added to bevacizumab reduced the risk of disease progression or death by 67%.

“This trial was designed to reflect everyday clinical practice using a global standard-of-care treatment with Lynparza,” said José Baselga.

“The results showed at two years nearly half of women with advanced ovarian cancer were progression-free with Lynparza added to bevacizumab as a first-line maintenance treatment, regardless of their biomarker status or surgical outcome.

“We are working with regulatory authorities to bring Lynparza to these patients as quickly as possible.”

Roy Baynes, senior vice-president and head of global clinical development, and chief medical officer of MSD Research Laboratories, added that PAOLA-1 was the second positive phase 3 trial involving Lynparza in the first-line maintenance setting for advanced ovarian cancer.

“Following the positive SOLO-1 trial, we are encouraged by the PAOLA-1 results which reaffirm AstraZeneca and MSD's ongoing commitment to explore potential treatment options for more women with ovarian cancer.”

Isabelle Ray-Coquard, principal investigator of the PAOLA-1 trial and medical oncologist at Centre Léon Bérard, as well as president of the GINECO group, said the goal of first-line, including maintenance, treatment for women with newly-diagnosed advanced ovarian cancer was to delay relapse.

“Unfortunately, the risk of relapsing is high, as two out of three women relapse within three years of initial diagnosis.

“In PAOLA-1, the results of Lynparza added to bevacizumab were significant and have the potential to change clinical practice in how women with advanced ovarian cancer are treated in the first-line maintenance setting.”