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At cancer conference, debate over speedy drug approvals in the spotlight

CHICAGO — Each year, oncologists and cancer researchers pack into the American Society of Clinical Oncology’s annual meeting to hear of the latest clinical results, often touted as breakthroughs or as “practice changing.”

On Sunday, however, it was an unsuccessful study that featured in the conference’s plenary session, usually reserved for findings of highest impact.

The trial in question, called ANNOUNCE, tested Eli Lilly’s Lartruvo together with chemotherapy against chemo alone in patients with soft tissue sarcoma, a rare and highly varied type of cancer.

A surprising 12-month survival benefit in an earlier study had led the Food and Drug Administration to provisionally approve the drug in late 2016, with the condition that Lilly run a larger, confirmatory test.

But results from ANNOUNCE, disclosed in February, showed people given Lartruvo lived no longer than those who received placebo — a blow to patients with few other treatment options, and a setback for Lilly’s oncology business.

“We were deeply disappointed when we saw the results from that Phase 3 study,” said Anne White, head of Lilly oncology, in an interview.

That ANNOUNCE was included in ASCO’s top showcase is unusual. Few negative studies make into the conference’s plenary session, with a 2009 presentation of a failed study testing Roche’s Avastin in colon cancer being another example.

ANNOUNCE’s inclusion is made further noteworthy by recent questions raised about the FDA’s accelerated approval program.

Cancer drugs are a regular beneficiary of the speedy OKs, often cleared for commercial use on the basis of tumor shrinkage or progression-free survival.

Whether that’s appropriate depends on who’s asked, but a study published this month in JAMA Internal Medicine stirred the debate anew. Findings showed a minority of accelerated cancer drug approvals are subsequently supported by data showing patients lived longer.

Maura Dickler, who Lilly hired away from Memorial Sloan Kettering Cancer Center last year to become the pharma’s vice president of late phase development, argues fast-advancing science supports the FDA’s current approach.

“The accelerated approval program is really critical to bringing good medicines to patients,” she said in an interview.

In the case of Lartruvo, the drug’s relatively benign toxicity profile means its early approval likely didn’t expose many patients to harm.

The drug’s use still came at a cost, however, as for two years doctors prescribed what’s now seen as an ineffective therapy. And Lartruvo, like many cancer therapies, wasn’t cheap.

“The flip side of the coin for accelerated approval is the financial burden to society,” said Jaap Verweij, a medical oncologist at the Erasmus University Medical Centre in the Netherlands, discussing the ANNOUNCE study at the plenary session.

Sales of Lartruvo since its approval in late 2016 through the end of 2018 totaled $520 million, according to financial results released by Lilly.

“[Accelerated approval] won’t work all the time — we know that — and in this case it unfortunately didn’t,” said Dickler at a plenary discussion session Sunday, estimating that Lilly had spent roughly $200 million on the ANNOUNCE study.

After the result, Lilly moved quickly to begin withdrawing Lartruvo from global markets and has set up a program to allow patients already on the drug to continue treatment if desired.

“What I’m really proud of — because there’s been a lot of discussion about accelerated approval — is the speed at which Lilly moved,” said White.

“We had that Phase 3 study already enrolled, we reported the data quickly just slightly over two years later. That’s not always the case with accelerated approvals.”

Debate is likely to remain, as more targeted therapies aimed at generic drivers of cancer growth advance through testing.

That’s something Lilly lacked with Lartruvo, but the drug’s early survival signal was too appealing for either the company or the FDA to ignore.

“We don’t expect to be right all the time,” said Patricia Keegan, an FDA official at the Office of Hematology and Oncology Products, speaking on an ASCO panel discussing the results. 

“As a matter of fact, we think if we never have a trial where it doesn’t confirm [the prior result], we’re probably being too conservative.”