Pascal Soriot has been attending the American Society of Clinical Oncology’s annual meeting for the past two decades.
This year’s conference, the AstraZeneca CEO told investors Monday, was “very special” for the company he has led since 2012. The British drugmaker, which not long ago lagged behind leaders in oncology like Merck & Co. and Roche, now has four blockbuster cancer medicines and a pipeline of promising drugs.
AstraZeneca’s recent successes were spotlighted at ASCO, with survival data for its lung cancer drug Tagrisso presented in a plenary session Sunday — the fifth year in a row the company has had a highlighted presentation at the meeting.
“We were trying to think about who else, as a company, has had five successive plenaries,” Soriot said. “We couldn’t find anybody, so we’re really quite excited.”
Alongside the Tagrisso data, AstraZeneca had late-breaking data presented for Lynparza, another targeted cancer medicine, as well as for Enhertu, an antibody-drug conjugate licensed from Daiichi Sankyo that analysts expect to eventually earn many billions of dollars a year.
All told, the company had 40% more abstracts on data from its cancer drug pipeline at this year’s ASCO than it did in 2019.
AstraZeneca’s progress reflects cancer research’s, noted Soriot. “When you compare with what we had 20 years ago, it is just amazing the number of options that are becoming available for patients,” he said.
Read on for a review of three datasets that drew attention at this year’s ASCO. BioPharma Dive also covered Novartis’ breast cancer drug Kisqali, Enhertu and Johnson & Johnson’s multiple myeloma treatment Carvykti.
A two-plenary study
Three years ago at ASCO, initial results from a study of Tagrisso in lung cancer, called ADAURA, were presented in a plenary session — the second in that string of five successive plenaries highlighted by Soriot.
Data from the trial, which was stopped two years earlier than planned, showed Tagrisso dramatically cut the risk of lung cancer recurrence when used after surgery in certain patients. The results quickly led to an FDA approval in this “adjuvant” setting and, in the time since, helped to boost sales of the drug to just under $5.5 billion last year.
But the data left questions about whether that “disease-free” survival benefit would translate to people living longer. Those questions were answered by the data Sunday, which showed that, at five years, adjuvant Tagrisso treatment cut the relative risk of death by 51% compared to placebo.
In absolute terms, Tagrisso lowered the risk of death by 10%, meaning about one more patient in 10 would be alive five years later through treatment with the drug.
It’s a major finding, and one that’s likely to further shift oncologists toward using Tagrisso in tandem with surgery when treating early-stage lung cancer that harbors mutations in the EGFR gene, the drug’s target.
"[The data] dispel the notion of equivalence between early treatment with [Tagrisso] and treatment on recurrence,” said Benjamin Solomon, a medical oncologist at the Peter MacCallum Cancer Center in Australia, during a discussion of the plenary data.
"They mandate testing for EGFR mutations in patients with early-stage non-small cell lung cancer,” he added.
Even so, Solomon highlighted a number of remaining uncertainties, including the role of chemotherapy and the optimal duration of Tagrisso treatment, which was given for a prespecified three years in the study. — Ned Pagliarulo
Standard-setting cell therapy
For much of the past 30 years, the treatment for large B-cell lymphoma following a relapse or resistance was the same: Chemoimmunotherapy and, if that goes well, a stem cell transplant.
Yescarta, a CAR-T therapy developed by Gilead Sciences, last year became another option with an FDA approval that for the first time moved the complex cellular treatments earlier than the last line of defense.
On Monday, researchers made a stronger case for Yescarta, presenting data that showed treatment reduced the risk of death by 27% compared to that decades-old standard. The benefit was apparent even though a considerable number of study participants on the control arm eventually received cell therapy outside of the trial’s plan.
“[Yescarta] is a second-line treatment option in this population on the basis of a significant improvement in survival, as opposed to a strategy of delaying cellular immunotherapy until after progression or an inadequate response to platinum-based chemotherapy,” the researchers wrote in The New England Journal of Medicine.
According to Gilead, about three of 10 patients eligible for Yescarta currently receive it, a number the company hopes this ASCO data will raise.
“We believe this is not only a differentiation point for Yescarta itself,” said Warner Biddle, head of commercial at Gilead’s cell therapy unit Kite, “but we fell it’s even more important for raising the validity of the class itself and hopefully establishing a new standard of care that that help increase that three out of 10.”
Yescarta competes with another cell therapy, sold by Bristol Myers Squibb as Breyanzi, that recently won approval for second-line treatment of large B-cell lymphoma. — Ned Pagliarulo
Pfizer’s PARP competitor
Pfizer already released the main findings of the TALAPRO-2 trial in prostate cancer, which paired its PARP inhibitor Talzenna with a drug called Xtandi in patients whose disease has spread and stopped responding to hormone therapies. The FDA is reviewing those results and is expected to decide on approval sometime this year.
New TALAPRO-2 data released at ASCO showed how well Talzenna will work in patients whose tumors have “homologous recombination repair,” or HRR, mutations that can now be treated with competing PARP inhibitors, Lynparza from partners AstraZeneca and Merck & Co. and Rubraca from Clovis Oncology. Those two drugs are used in patients with these mutations once their disease has progressed on Xtandi or on Johnson & Johnson’s Zytiga.
(Lynparza was also recently cleared for use earlier, alongside one of those two medicines.)
In these HRR-positive patients, who have never been treated with Xtandi or similar drugs, Talzenna plus Xtandi reduced the relative risk of progression by 55% when compared with a placebo plus Xtandi. In the broader all-comers patient group in TALAPRO-2, the drug reduced the risk by 37%.
After progression on Xtandi or Zytiga, Lynparza plus Zytiga reduced the risk of progression by 76% when compared to Zytiga alone in patients with a specific HRR mutation called BRCA. In a similar trial, Rubraca reduced the risk by 50% in BRCA patients.
While TALAPRO-2 didn’t pre-specify an analysis of BRCA mutations alone, an “exploratory” analysis that doesn’t measure statistical significance found that patients with BRCA mutations saw an 80% reduction in risk when receiving Talzenna plus Xtandi.
“Our study design was robust and I think it accounted for a lot of learning of earlier PARP inhibitor trials,” Suneet Varma, Pfizer’s global head of oncology, said in an interview. — Jonathan Gardner