July 2019 Ask the Expert: Alpelisib and Other Treatments for Metastatic Hormone Receptor-Positive Breast Cancer

July 29, 2019

The listeners to New Approval for Metastatic Breast Cancer: Alpelisib, Living Beyond Breast Cancer’s July 22, 2019, webinar, had more questions than we had time to answer. Medical oncologistinfo-icon Adam Brufsky, MD, PhD, agreed to answer the remaining questions in writing. To learn more about alpelisib (Piqray), CDK 4/6 inhibitors, and other treatments used today for metastaticinfo-icon hormone receptorinfo-icon-positive breast cancer, listen to Dr. Brufsky’s full recording.

Remember: we cannot provide diagnoses, medical consultations or specific treatment recommendations. This service is designed for educational and informational purposes only. The information is general in nature. For specific healthcare questions or concerns, consult your healthcare providerbecause treatment varies with individual circumstances. The content is not intended in any way to substitute for professional counselinginfo-icon or medical advice.

If alpelisib (Piqray) is effective, how long will it continue to be effective?

On average, at least a year (medianinfo-icon progression-free survivalinfo-icon is one year), and we think perhaps longer.

I have the PIK3CA mutation. Will the combination therapy work if I have had fulvestrant (Faslodex) previously for two years with palbociclib (Ibrance) in 2017?

We are not sure, but I would give Faslodexinfo-icon with the alpelisib (Piqray).

Can you take alpelisib (Piqray) after being on fulvestrant (Faslodex) alone? What about after everolimus (Afinitor)?

You can, if you have a PI3K mutationinfo-icon, which we would test by DNA sequencing of cancer DNA found in your blood.

I’ve heard about the BYLieve clinical trial of letrozole (Femara) and alpelisib (Piqray). Could you switch to that combination if you had progression on fulvestrant (Faslodex) and Piqray?

The BYLieve trial is preliminary, but the results of Femarainfo-icon and alpelisib in this trial do look promising. I would still use fulvestrantinfo-icon (Faslodexinfo-icon) with Piqray at this point.

What is the optimal sequence for using alpelisib (Piqray)? Would it be before or after trying capecitabine (Xeloda)?

You can use it before or after Xelodainfo-icon, as long as you have a PI3K mutationinfo-icon in the tumorinfo-icon DNA. I like to use it after letrozoleinfo-icon (Femarainfo-icon) and a CDK 4/6 inhibitor like palbociclib (Ibrance).

Many of us have listened to Dr. Lewis Cantley’s talk on the keto diet and PIK3 drugs and the benefits. Do you agree with a low carb/keto diet to lower insulin production to keep glucose low?

This diet is in clinicalinfo-icon trials but it could be useful now to consider.

My understanding is that the reason other PI3K inhibitors like taselisib did not work was because they did not screen out patients with insulin resistance. Did the SOLAR trials of alpelisib (Piqray) do so?

I do not believe so, and I am not sure that SANDPIPER screened out patients with insulin resistance.

Is there a complementary action between PIK3 and TP53 mutations?

Not that we know of.

Will having a KRAS mutation inhibit a PIK3 inhibitor?

Not that I know of. It would not stop me from prescribing alpelisib (Piqray).

I have heard of women on palbociclib (Ibrance) who have progression, go off the treatment, and then may come back on it and it works again. Have any of the people in the alpelisib (Piqray) study gone back to Ibrance?

There are no data on this, so we do not know.

I am starting alpelisib (Piqray) this week. I've had no issues with glucose levels in the past and don't have results yet from my fasting glucose this weekend. I'm worried about diarrhea and how the BRAT diet is recommended, which is high carb. I currently eat plant-based foods and have no desire to eat meat. Are probiotics helpful in diarrhea caused by Piqray?

We are not sure, and I would be careful with probiotics in this situation.

Can you say more about the efficacy of alpelisib (Piqray) for patients with HER2 mutations? Are these tumors less receptive to Piqray than those that are HER2 negative? What are the names of the trials available of PIK3 inhibitors for hormone receptor-positive and HER2 positive metastatic breast cancer?

There are currently trials testing anti-HER2 agents with alpelisib, but they are not complete, so we do not know if they will work well together. I am not sure of the names, but you can search NCIinfo-icon PDQ for these. [Editor’s note: Here are trials on clinicaltrials.gov, some based in the U.S. and some abroad.]

Is there a test to determine which isoform (alpha vs the other three) of PIK3CA is mutated?

There is no clinicalinfo-icon test at this point that I am aware of.

I have been on alpelisib (Piqray) for over 3-1/2 months. I had rash (grade 3) and was given prednisone (per protocol) but the combo put me into DKA (diabetic ketoacidosis, a serious side effect of diabetes). Since then I have been on insulin and metformin. I have read extensively that insulin is not good with a PIK3 inhibitor. But my scans show significant regression. What is the long-term use of insulin with this drug? Will it inhibit the effectiveness of Piqray? I had no signs of insulin resistance before starting Piqray.

I am happy it is working, and in this case insulin is not inhibiting alpelisib.

Why not prescribe metformin as part of treatment, if treating the patient as though they have diabetes when taking aleplisib (Piqray)?

Most people end up on metformin to control the high sugars with alpelisib.

How much does alpelisib (Piqray) cost per month for patients?

This really depends on your insurance plan and coverage, but the price to insurance (not to the patient) is about $10,000-$15,000 per month. [Editor’s note: The list price for a 28-day supply is $15,500. Novartis, the maker of alpelisib, has patient assistance programs and a Patient Support Line. Visit the website for more information.]

With progression on a CDK 4/6 inhibitor, besides trying abemaciclib (Verzenio) as monotherapy, is there evidence for waiting (and how long?) and trying the same CDK inhibitor again?

There is no evidence for waiting, but there are trials of staying on the same CDK 4/6 and trying another hormonal therapyinfo-icon as a strategy. [Editor’s note: We found four U.S. trials on clinicaltrials.gov that look at how CDK inhibitors may be used after the cancer progresses with a hormonal therapy and CDK inhibitor.]

Would it make sense to try abemaciclib (Verzenio) after progression with palbociclib (Ibrance)?

Our group and others have presented data on this strategy and will publish it soon. This could be a possible idea to pursue.

What is your experience with patients switching from one CDK 4/6 inhibitor to another due to side effects?

The CDK 4/6 generally still works.

Do any of these treatments work if the cancer has lower ER positivity (10 percent to 40 percent, depending on where the tumor is biopsied)?

These therapies do work with low ERinfo-icon.

Why is it good to push chemo out a few years after a metastatic diagnosis? Is it to increase survival and the number of treatments to try?

Less side effects and yes, to increase the number of possible treatments.

Is the reason CDK 4/6 inhibitors have so many GI (gastrointestinal, or stomach) issues because of the high cell division rate in the GI tract or because the drug is cleared through the colon?

These agents can affect cellinfo-icon division in the large intestine, and some of them do come in contact with the colonic wall mucosa.

I have ER positive lobular breast cancer with mets to my ovary with no measurable tumor. I'm on palbociclib (Ibrance) and fulvestrant (Faslodex) with no progression. I have a PIK3 mutation. Happy to stay on drugs with low side effects that seem to be working. I’m interested in the use of liquid biopsy to determine progression, instead of waiting for a tumor to grow big enough to detect a slow-growing cancer. You make it sound like liquid biopsy is common and easy but that's not what my doc says. Thoughts?

Liquid biopsyinfo-icon is not that difficult, but my own biasinfo-icon would be to wait for progressioninfo-icon by scans, since we are all not quite yet in agreement as to what emergence of a mutationinfo-icon in a liquid biopsy actually means.

Can everolimus (Afinitor) be used if it failed in a pre-metastatic setting?

Yes, since it depends on the endocrine therapyinfo-icon it is being used with.

Can you clarify whether the Rb1 mutation is from ER resistance or CDK 4/6 resistance?

It can come from CDK 4/6 resistance.