Accelerated Approval Now Full for Pembro in Bladder Cancer

Zosia Chustecka

September 01, 2021

Accelerated approvals of oncology drugs based on response data are controversial, because subsequent trials have often failed to show a clinical benefit. This has led to a spate of withdrawals of such accelerated approvals, including those for nivolumab in liver cancer and pembrolizumab in small cell lung cancer.

But one such accelerated approval has now been converted to a full approval, with a small label change, by the US Food and Drug Administration (FDA).

The new full approval is for pembroilizumab (Keytruda) for first-line use for patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for any platinum-containing chemotherapy. (The small label change is that mention of PD-LI status and testing for this have been removed.)

The move is in accordance with recommmendations by experts at a recent meeting of the Oncologic Drugs Advisory Committee. They voted 5-3 in favor of this accelerated approval staying. They also voted 10-1 in favor of another immunotherapy, atezolizumab (Tecentriq), for the same indication.

One of the arguments put forward to support these accelerated approvals staying in place is that there is an unmet need in this population of patients who are ineligible for platinum chemotherapy.

But this argument doesn't hold water ― the mere existence of one of these negates the "unmet need" argument for the other, wrote Bishal Gyawali, MD, PhD, from Queen's University, Kingston, Ontario, Canada, in a Medscape commentary on why the FDA's accelerated approval pathway is broken.

"Even if there is a genuine 'unmet need' in a particular setting, these drugs did not meet the standard of improving survival. An unmet need doesn't imply that the treatment void should be filled with a drug that provides nothing of value to patients," Bishal wrote.

"When we talk about an unmet need, we are speaking of drugs that provide a clinical benefit; any true unmet needs will continue to exist despite maintaining these approvals," he argued.

After obtaining the accelerated approval for pembrolizumab for patients with bladder cancer who are not eligible for cisplatin-containing chemotherapy, the manufacturer (Merck & Co) carried out a subsequent clinical trial but conducted it in patients who were eligible for platinum-containing chemotherapy (Keynote 361). However, this trial did not meet its prespecified dual primary endpoints of overall survival or progression-free survival in comparison with standard-of-care chemotherapy, the company noted in a press release.

"We are working with urgency to advance studies to help more patients living with bladder and other types of cancer," commented Scot Ebbinghaus, MD, vice president of clinical research, Merck Research Laboratories. The company said it has "an extensive clinical development in bladder cancer" and is exploring pembrolizumab use in many settings.

In addition to the new full approval for the first-line indication for patients who are ineligible for platinum chemotherapy, pembrolizumab has two other approved indications in this therapeutic area:

  • the treatment of patients with locally advanced urothelial carcinoma or mUC who experience disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy; and

  • the treatment of patients with bacillus Calmette-Guérin–unresponsive, high-risk, non–muscle invasive bladder cancer with carcinoma in situ, with or without papillary tumors, who are ineligible for or have elected not to undergo cystectomy.

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