Merck & Co.’s Keytruda may just be on its way to earlier use in head and neck cancer, an area where it once faced some questions. On Wednesday (July 25, 2018), the giant drugmaker said that in a Phase 3 trial in previously untreated patients, Keytruda topped a standard-of-care regimen that includes Eli Lilly’s Erbitux at extending overall survival in patients with tumors expressing a certain level of biomarker PD-L1.
The data came from an interim analysis of the trial that also showed Keytruda hadn’t yet met the study’s other primary endpoint, which measures time to cancer progression. But overall survival is often considered the gold standard in cancer trials, and Merck will be flaunting that to regulators.
Presently, Keytruda is approved in head and neck cancer but only in patients whose disease has worsened on or after chemo. And after gaining that conditional approval, last July it failed to prove it could extend the lives of those patients.
As analysts pointed out at the time, however, that letdown was narrow, coming just short of statistical significance. The FDA kept the approval in place, and now, Merck has the data to back it up.
If Merck can win a new indication from the FDA, it could gain access to a patient pool that grows by about 63,000 US cases per year. And that’s a group Keytruda’s rival, Bristol-Myers Squibb’s Opdivo, can’t currently treat because its approval only extends to previously treated patients.
Merck isn’t just pursuing the monotherapy route in head and neck cancer. The latest results come from a trial called Keynote-048, a study that’s also examining Keytruda as part of a cocktail containing platinum chemo and chemo drug 5-fluorouracil.
The latest win builds on what’s already been a big summer for the I/O hit. In June, it received approvals in cervical cancer and a rare type of non-Hodgkin lymphoma.
I’ve written before about a close friend I’ll call Bob, who was diagnosed with stage IV (metastatic) gastric cancer and was put on a treatment protocol of…chemotherapy, surgery, chemo…cure! The medical institution is one of the top five cancer centers in the US.Steve's Take: A sobering reminder that even some highly-touted #cancer therapies, like #Keytruda, are very far from cures Click To Tweet
After surviving the first round of 12 cycles of pernicious chemotherapy (decades-old oxaliplatin, together with fluorouracil and folinic acid), the follow-up CT scan suggested that Bob undergo what’s called cytoreductive surgery (CRS) with HIPEC. In English, this means Bob’s abdomen would be opened and the surgeon would remove all the cancer he could see, including his entire stomach. Then the abdomen would be rinsed with heated oxaliplatin before closing him up. Talk about a life-changing event.
This is essentially what was entailed in a presentation I reported on from the ASCO meeting in June.
Bob’s specific type of gastric cancer is the most unfriendly, with a very poor prognosis, namely, a 2-year survival rate of about 4%. Bob’s tumor profile report from that sector’s leader, Caris Life Sciences, said the profile made Merck’s Keytruda (pembrolizumab) the chief treatment option. But Bob’s oncologist said he believed the chemo/surgery/chemo approach had to fail first before he would even consider putting Bob on Keytruda.
I have to hand it to Merck that the wild success of Keytruda hasn’t gone to the heads of the C-suite group, or board—yet.
Merck still has a cluster of its Keynote clinical trials of Keytruda underway, even as the anti-PD-1 drug has garnered 10 FDA-approved indications, notes STAT News. But kudos to the company for frankness: The many years of follow-up are showing that for every patient who seems to be cured there are many more who aren’t.
And to the credit of their scientists, Merck owned up to that fact.
According to five-year data from a trio of Keynotes on patients with advanced melanoma, of 655 patients who entered the trial, 412 have died. By two years, half had died. Median survival was better in treatment-naive patients, though: just under 39 months in those who hadn’t received any therapy before starting Keytruda. The data represent the longest follow-up for the med so far in any cancer.
Definitely a sobering reminder that even some highly-touted therapies are very far from cures.
Then I was struck by the calm, stoic objectivity of the HIPEC study author, Dr. Quenet, announcing that the 15-year-old HIPEC routine, “…does not provide added benefit over surgery.”
Update on Bob’s treatment:
Going back to my friend, Bob, his oncologist and surgeon stood steadfastly by their recommendation for the removal of his entire stomach and other involved organs, followed by the rinse of his abdomen with the heated chemo liquid. Bob knows that losing his stomach will be a life-altering event. And the HIPEC rinse may not only not work, but he may also have life-threatening complications as a result of it.
He figured if he can get five, who knows, 10 years, where he can live a relatively “normal” life before succumbing? That would be an acceptable tradeoff for seeking a “cure,” with all the surgery and HIPEC and post-op complications.
Bob decided to get a second opinion from the chief oncologist of another fine hospital in the metropolitan region where he lived. Bob had heard “through the grapevine” that this oncologist was a believer in the curative promise of Keytruda and other checkpoint inhibitors like Bristol-Myers’ Opdivo. Maybe immunotherapy with Keytruda would knock back most or all of his cancer and he could keep his stomach.
Meetings like the recent ASCO event are replete with promise for those cancer patients undergoing new treatments that work. But as one wades through the data in the papers, it becomes clear that they don’t work for the vast majority of patients, and in some cases, actually kill a non-insubstantial percentage of them.
Beneath the quandary, though, in each instance whether to take the established medical treatment or just let nature take its course, is the quality-of-life issue. This seemingly should be addressed directly at worldwide meetings like ASCO. But I don’t see it mentioned, as though that’s not the purpose of the plethora of trials and papers wherein most stage IV patients die from the complications of their treatment than the medicines being tested. That seems wrong to me.
Back to Bob. Put simply, Bob got the second opinion and…the oncologist said…he agreed completely with the surgery that had been recommended. And when Bob asked about Keytruda he was told, “The realm of science with Keytruda and gastric cancer is evolving.” He made it clear his recommendation was, “Don’t resort to still experimental immunotherapy (Keytruda) when you have another option,” namely the complete gastrectomy.
Last week Bob underwent a cytology test to confirm that he was a candidate for the surgery. The hope was that the cancer was now confined to his stomach and that turned out the result. Although initially crushed that the second opinion confirmed the surgery option and not immunotherapy, the conviction was so strongly rendered that Bob was relieved there was total consensus. He finally realized he never really wanted to see that there wasn’t a path to a “good” outcome where he didn’t lose his stomach in the process. (Apologies for the triple negative.)
Like Bob, sometimes, you don’t see a specific red flag, yet you keep feeling uncomfortable about the diagnosis or treatment course your physician sets forth. While the physician has a better medical education, you shouldn’t discount your feelings and your knowledge of your own body.
Getting a second opinion can reveal a mistake or, in Bob’s case, confirm your physician’s original diagnosis and plan. Either way, taking the step of seeking out another opinion can give you the peace of mind you need to decide what’s best.
I’m mindful that use of immunotherapy like Keytruda isn’t yet entirely out of the question in Bob’s situation–post-surgery. So be on the lookout for my next update.