Metastatic cancer is such a tough foe that even with powerful new targeted drugs, big advances in survival are far and few between. I’ve been covering cancer drug development for years, and in my experience, oncologists often get excited if a drug improves median survival by just a few months.
So when news came this weekend that a new targeted drug combo bolstered the median survival in advanced bladder cancer from 16.1 months to 31.5 months in a big study, it caught my attention. It’s not often that you see a survival difference this dramatic — in this case, potentially adding more than a year to someone’s life.
It’s been a particularly long time since there were significant advances in treating advanced bladder tumors. Toxic chemotherapy has remained the primary initial treatment for decades. This type of tumor is “aggressive and generally incurable,” researchers wrote in one 2021 New England Journal of Medicine report describing earlier results from one of the targeted drugs in the new combo.
There are around 82,000 new cases of bladder cancer in the US each year, and roughly 17,000 deaths, according to the American Cancer Society. Smoking is a prime risk factor. Most cases are caught in the early stages where it is highly treatable with surgery. But for the minority of cases that are locally advanced or have metastasized, the prognosis historically has been terrible.
The new regimen eliminates traditional chemotherapy and replaces it with Seagen’s targeted drug Padcev, combined with Merck & Co.’s immune therapy drug Keytruda. Padcev is an antibody drug-conjugate, a new type of “magic bullet” treatment that uses targeted antibodies to deliver a blast of cancer-killing chemicals directly to a tumor.
If old fashioned chemotherapy is akin to bombarding the body with unguided artillery, antibody drug conjugates are more like precision-guided smart bombs. They certainly don’t eliminate side effects, but they do attempt to direct more of that cancer-zapping firepower at the tumor.
While antibody drug conjugates are a complicated technology that took scientists at Seagen and elsewhere many years to perfect, they have recently become one of the hottest areas of cancer drug development. Earlier this year, Pfizer agreed to buy Seagen for $43 billion to gain access to its portfolio of antibody-drug conjugates. In a separate deal, Merck & Co. last week announced it would pay up to $22 billion—including $4 billion up front—for rights to commercialize three experimental antibody-drug conjugate drugs from Daiichi Sankyo in all parts of the world except for Japan.
The Padcev bladder cancer results are “very impressive,” Andrea Apolo, chief of the Bladder Cancer Section in the Genitourinary Malignancies Branch at the National Cancer Institute’s Center for Cancer Research, told my colleagues Naomi Kresge and Nacha Cattan, in their story this weekend. “I think it will become the standard of care for bladder cancer.”
The findings from the Padcev study were presented on Sunday at the European Society for Medical Oncology’s annual meeting. In another bladder cancer trial at the same meeting, oncologists reported that a combination of Bristol-Myers Squibb’s Opdivo with chemotherapy produced longer survival than chemo alone, though the magnitude of difference was not as dramatic as in the Padcev trial.
Seagen, which developed Padcev with Astellas Pharma, told Bloomberg that the companies would seek US regulatory approval for the new combination this year for initial treatment of metastatic bladder cancer. The companies have been collaborating with Merck on the combination since 2019. The regimen is already approved in the US for certain patients ineligible for traditional chemotherapy.
All of this is great news for bladder cancer patients and their families who need better options.
“Frankly, we haven’t seen results like this ever before,” Jonathan Rosenberg, an oncologist at Memorial Sloan Kettering Cancer Center involved in the Seagen study told me in an email.
Rosenberg, who has consulted for Seagen, is hopeful that “a significant portion” of the patients will remain in remission for years to come. — Robert Langreth
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