Patient-Centered Dosing Article

[Bestbird]

Delighted to share this article in Cancer Today Magazine about Patient-Centered Dosing! Dr. Hope Rugo, a member of the Patient-Centered Dosing Initiative Advisory Board, was interviewed along with myself.

The message is gaining momentum!

cancertodaymag.org/Pages/ca...

[Thrifty51]

Thank you Bestbird for being our advocate. Looks like we are the ones who need to school oncologists on this, especially if they are not part of a major cancer center.

Best regards,

Audrey

[Bestbird in reply to Thrifty51]

Audrey, thank you! Agreed that patient education is very much needed regarding dosing, and that will be one of the PCDI's major areas of focus in 2021!

[Sunnydrinking]

Well done Anne - all your hard work & research is paying off.

You do so much for us ladies with MBC and I’m always looking at your book for information.

Jo

[Andersl]

Thank you for sharing this article. I agree with the sentiments described. I hope the information gets heard far and wide. Time for change!

[Corgi3]

Thank you for sharing this information with us! Much appreciated!

Bev

[LibraryGeek]

Anne, thanks for your tireless work for us all. This is very encouraging.

Jackie

[stardust1965]

Anne, I am on the lowest does of 75mg of Ibrance having started on 125mg for about 8 months then lowering to 100mg for a few months before finding 75mg is the dose that works best for me. My neutrophils are effected and the fatigued I suffered on the higher dose was just awful. It was a game changer to be on the lowest dose. I’ve had “partial response” and “stable” scans ever since. My de novo two year anniversary is coming up next month and I feel (mostly) good. So I totally agree with your article. Thank you. Vicki

[Bestbird in reply to stardust1965]

Vicki, congratulations on your upcoming two-year de novo anniversary, and wishing you decades more!

[8576]

This is so great. I learned that is an important consideration when starting on Ibrance. I had to go to the lowest dose at minimal days to get results that would work for me. If lower dosages works for Ibrance why not for any meds which can be reduced.

I am not sure I agree with the idea of starting on the lowest dose. It somehow feels better to try the higher dose first and work down.

But wonderful exciting news.

Cheers, June S.

[Bestbird in reply to 8576]

June, thank you for your thoughtful response! One point of clarification: We certainly are not advocating for patients to start on the lowest dose. What we're encouraging patients to do is to discuss dosage options with their physicians, and jointly decide upon which dosage is optimal for that patient based upon their unique characteristics. So the decision may ultimately be the Maximum Tolerated Dose, or an allowed lower dose, based upon the patient's physical, situational, and psychological circumstances!

[8576 in reply to Bestbird]

Thanks for the clarification. I did get it wrong somehow. Read it rather quickly. Anyhow I think it is wonderful and makes so much sense to modify dosages wherever possible.

It is amazing to me that our bodies can tolerate all the meds that are thrown at us! When I think about the series of drugs we go through over many years just to keep to beat Cancer down it is truly a wonder. Thanks for your great contribution of information.

Cheers, June S.

[Bestbird in reply to 8576]

June, you raise a great point! Because today's drugs tend to be more effective, we generally remain on treatment longer even though MBC cannot be cured. Cumulative treatment-related toxicities can indeed be formidable, which is the reason MBC patients should be treated with palliation and disease control in mind based upon each patient's unique individual characteristics.

[Rhwright12]

Thanks for sharing!

[mariootsi]

Thank you for posting this article. Very informative

[WordNerdSharron]

Thank you, Anne!

[Hidden]

Thank you Anne, that is very encouraging to hear. I must admit I believed in the higher the dose the better - not now!!

Thanks for all the hard work

Clare x

[Bestbird]

Many thanks for taking the time to read the article and for your responses!

Although more data is needed regarding the efficacy of lower dosages, below are the studies I've been able to find. In all cases of these specific drugs, the lower allowed doses have been shown to be as effective than the MTD while precipitating fewer and/or less severe side effects.

Please bear in mind that for some patients, the Maximum Tolerated Dose ("MTD") may be the best dose. And for other patients a lower allowed dose may be better. The point is to be aware that for most MBC therapies (except for endocrine therapies) multiple dosages may be available, and to discuss potential dosing options with one's doctor.

1. Abraxane (Nab-Paclitaxel) – Dose reduction after induction chemotherapy:

The Phase II SNAP trial was designed to evaluate the efficacy of alternative chemotherapy schedules for prolonged administration in HER2-negative metastatic breast cancer (MBC), after a short induction at conventional doses. Between April 2013 and August 2015, 258 women untreated with chemotherapy for their HER2- MBC were randomly assigned to receive three different maintenance chemotherapy schedules after three cycles of identical induction chemotherapy: Arm A, nab-paclitaxel 150 mg/m2 days 1 and 15 Q28; Arm B, nab-paclitaxel 100 mg/m2 days 1, 8 and 15 Q28; Arm C, nab-paclitaxel 75 mg/m2 days 1, 8, 15 and 22 Q28. Induction was three cycles nab-paclitaxel 150/125 mg/m2, days 1, 8 and 15 Q28. The primary objective was to evaluate the efficacy of each maintenance schedule in terms of progression-free survival (PFS) as compared with the historical reference of 7-month median PFS reported by previous studies with first-line docetaxel. Median PFS in Arm A was 7.9 months; Arm B was 9.0 months, and Arm C was 8.5 months. Grade ≥2 sensory neuropathy was reported in 37.9%, 36.1% and 31.2% of the patients in arm A, B and C, respectively. ncbi.nlm.nih.gov/m/pubmed/2...

2. Afinitor (Everolimus) – Varying starting dosages:

MBC patients treated with the combination of everolimus and exemestane at Moffitt Cancer Center were subdivided into 3 groups: 77 patients were started on 10mg daily, 29 patients were started on 7.5mg daily, and 31 patients were started on 5mg daily. There was no significant difference in PFS between starting the recommended dose or a lower dose. Patients initiated on lower doses were less likely to require dose reductions or discontinue due to toxicity, even with later dose increases. If oncologists are more comfortable starting a lower dose, survival may not be adversely affected and patients may be more compliant, deriving a prolonged benefit from the combination. ascopubs.org/doi/abs/10.120...

68 HR+, HER2- MBC patients were given 5mg of Afinitor with Aromasin. After a median follow up of 14 months, PFS was 5.3 months and OS was immature. 16 patients (23.5%) were at the first or second-line and 52 (76.5%) were at third line or later. PFS for the first and second-line was significantly longer than that for the third-line or later (12.9 months vs. 4.6 months). 11 patients (16.2%) achieved partial response, 42 patients (61.7%) had stable disease, and 15 patients (22.1%) reported progressive disease. The ORR and CBR were 16.2%, 35.2%, respectively. As per the BOLERO-2 trial which combined 10 mg of Afinitor with Aromasin in the second-line setting, the average PFS for patients taking the combination was 7.8 months. sabcs18.posterview.com/nosl...

3. Ibrance (Palbociclib) – Randomization with standard vs. lower dose at start of treatment; Results after dosage lowered upon AE:

A Phase II study that randomized 72 HR+ HER2- MBC patients to receive Ibrance in either a 125 mg or 100 mg dose in combination with physician’s choice of fulvestrant or tamoxifen concluded that the 100 mg dose was associated with a lower rate of grade 3 or 4 neutropenia. Furthermore, both Progression Free Survival and clinical benefit were the same in both groups. Dr Hope Rugo was the lead investigator. targetedonc.com/news/reduce...

In a slide entitled, “PALOMA-3: Effect on PFS of Dose Reductions due to Neutropenia” presented by Dr. Sara Hurvitz at Clinical Care Options Oncology on June 18, 2020, it was reported that the PFS observed between patients who had ≥ 1 Ibrance dose reduction vs. no dose reduction due to neutropenia was identical at 9.5 months.

4. Kisqali (Ribociclib) Dose Reduction after AE: As per SABCS 2018 Poster P6-18-06 on the next page: Conclusion: “The results from across the MONALEESA program suggest that the efficacy of ribociclib was maintained regardless of dose intensity,” and that patients’ Overall Response Rates and Clinical Benefit Rates were superior on the reduced dosages.

5. Xeloda (Capecitabine) – Support of starting patients at lower dosages:

An analysis of dose modification and outcomes from four Phase II capecitabine monotherapy trials, one Phase III capecitabine/docetaxel combination trial, and an analysis of consecutive MBC patients who received capecitabine outside of a clinical trial concluded that reduced capecitabine doses were associated with a lower incidence of treatment-related adverse events, specifically hand-foot syndrome, diarrhea, and stomatitis. Furthermore, time to disease progression and overall survival were similar, or even slightly longer, among patients who received lower vs. full-dose capecitabine in all of the studies reviewed. Together, these data support the practice of dose-reducing capecitabine, including the possibility of starting at a lower dose (<1250 mg/m 2 twice daily), to reduce the incidence of adverse events without compromising efficacy. clinical-breast-cancer.com/...

At the University of Southern California (USC) hospitals, capecitabine is routinely prescribed at dosages as low as 600 mg/m2 twice daily, with a majority of MBC patients receiving a flat dosage (not adjusted for BSA) of 1000 mg twice daily. In a review of 84 patients who received a median capecitabine dosage of 565 mg/m2 twice daily, the median PFS among the 62 patients with measurable disease was 4.1 months), which was similar to the median PFS values (4.4 months; 4.2 months) for single agent capecitabine reported in the two major trials with similar eligibility criteria. Furthermore, only 2 patients (2.4%) discontinued capecitabine due to toxicity, supporting the hypothesis that starting treatment at low dosages minimizes side effects while preserving efficacy. gotoper.com/publications/aj...

6. Verzenio (Abemaciclib) Randdomized lower starting dose:

The Phase 2 nextMONARCH study enrolled 234 HR+, HER2- MBC patients who had previously received 2 or more chemotherapy regimens (1 or 2 of which had been received in the metastatic setting). Patients were randomized to receive either: Verzenio at 150 mg twice daily plus Tamoxifen once daily (arm A), 150 mg of Verzenio twice daily (arm B), or 200 mg of Verzenio twice daily (arm C), which is currently the FDA-approved Verzenio dose when taken as a monotherapy. Results showed a median Overall Survival of 24.2 months with the combination of Verzenio and Tamoxifen (arm A), 20.8 months for the 150 mg twice daily monotherapy dose (arm B), and 17.0 months for the 200 mg twice daily monotherapy dose (arm C). Treatment-related Adverse Events (AEs) were slightly lower on the Verzenio 150-mg monotherapy dose (97.5%) than on the 200 mg monotherapy dose (98.7%). From: onclive.com/view/abemacicli...

[8576]

Just wanted to add my thoughts to this discussion. I think it is so great to pay attention to doses for each person. The huge benefit is the reduction in side affects, like overwhelming fatigue and more.

I can't stress enough, that we should not hold back on asking questions and pressing for information on decisions.

In my personal experience, in the face of confusion or indecision, I sought out a second opinion from a very experienced and wise, well respected oncologist at another hospital. Produced amazing results for my oncology dept. (Yes, I mean the whole dept. )

In another incident, I was in being assessed for radiation and the doctor was ready to set it up. I asked a totally innocent question unrelated to the radiation treatment and that simple question ended up turning the whole oncology dept. again. I was truly amazed. I did not need that radiation. I know this sounds bad for our oncology dept. They are well respected and do a great job but they are seeing hundreds of patients and I believe it is the same all over. They can't possibly be always on top of this whole complex thing called Cancer.

Hope some of this helps, All the best to everyone.

Cheers, June S.