Reversing resistance to PD-1 inhibitors with combination immunotherapy in patients with advanced melanoma (ipilimumab + nivolumab nearly 262% better progression free survival & 311% better rate of response)

Medical Xpress / 2022 Annual Meeting of the American Association for Cancer Research (AACR) ^ | Apr. 9, 2022 | SWOG Cancer Research Network / Ari Vanderwalde, MD, MPH et al

[ConservativeMind]

Patients with advanced melanoma whose cancer does not respond to treatment with widely used immunotherapy drugs known as PD-1 inhibitors are often switched to treatment with a second type of immunotherapy drug—a CTLA-4 inhibitor such as ipilimumab. New results from show that these patients are more likely to benefit from ipilimumab when it is given in combination with the PD-1 inhibitor nivolumab than when given alone.

Patients in the study who got an ipilimumab and nivolumab combination had longer progression-free survival (PFS) time than patients who were treated with ipilimumab alone (six-month PFS estimates of 34% vs 13%). The overall rate of response to treatment was also greater on the combination arm (28% vs 9%).

"We know patients receiving PD-1 inhibitor monotherapy do better than patients receiving ipilimumab alone," [Ari Vanderwalde, MD, MPH] said. "This study answers the question of whether patients who progress on PD-1 agents can continue the PD-1 agent in combination with ipilimumab, or if they should be switched to ipilimumab altogether."

The trial enrolled patients with advanced melanoma treated with anti-PD-1 or anti-PD-L1 immunotherapy drugs and had not received an anti-CTLA-4 drug. In all cases, the patients' cancer had not responded to this therapy and had become worse or had spread, either while the patient was on this therapy or after the patient had stopped the therapy.

These patients were randomized to receive either ipilimumab alone for 12 weeks or a combination of ipilimumab and nivolumab for 12 weeks followed by monthly nivolumab for two years.

"More than 50% of patients don't achieve a response to PD-1 inhibitors," Vanderwalde said. "These primary refractory patients have had limited evidence-based options. SWOG S1616 should establish the combination of ipilimumab and nivolumab as the standard in patients who have progressed on first-line therapy that did not contain ipilimumab."

[ConservativeMind]

A simple change to combining treatments, rather than the normal practice of using one, then only the other, exclusively, made all the difference, in just a 12 week time span.

[ConservativeMind]

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[doragsda]

I had to read the abstract to understand what they were doing, but this was targeted at patients who had not previously had ipi treatment, just nivo.

My wife is a stage 4 melanoma survivor (with brain mets). She was diagnosed stage 4 when they found two melanoma brain tumors in 2017 (she had had a melanoma removed from her leg 6 months prior and he been given an all clear at that time).

She was treated with ipi + nivo for 4 infusions and then switched to nivo alone for two years. The ipi frequently has serious side effects so they limit it to 4 or fewer treatments but just that amount has a huge benefit.

Immunotherapies have been a game changer for melanoma, as chemotherapy and most other treatments have never worked very well. If she had been diagnosed 5 years earlier she likely wouldn’t have survived it, now she’s cancer-free.

[ConservativeMind]

That is amazing news and a real praise to God.

So few can say they survived Stage 4 brain cancer.

Thank you for sharing. What a true blessing!

[FroggyTheGremlim]

I have had melanoma. Treated for 2 years with pembrolizumab (Keytruda) + metformin (immunotherapy).

I had 2 small lesions on my liver plus a lymph node tumor which was removed.

My last treatment was in January this year. In February, a head-to-toe PET scan came out negative.

The treatment had NO negative side effects for me. A few years ago, this melanoma would have killed me.

Jimmy Carter had the same treatment - his melanoma was worse, it had traveled to his brain. Thank God mine didn’t. He is now 96 years old.

Immunotherapy worked for me. I hope advances in such treatments can be found for other forms of cancer.

[AuntB]

My daughter has melanoma. She refuses to see an oncologist. Goes to a dermatologist who us 85 years old who just cuts chunks out of her.

No she won’t listen to anything

[ConservativeMind]

That’s truly wonderful to hear.

Thank you for sharing. You provide hope to others.

[WASCWatch]

Melanoma treatment has changed a lot. She should get a consult at MD Anderson. There are treatments that may very well cure her.

[AuntB]

I know, it breaks my heart. She’s stubborn and if I suggest it she does just the opposite.