Bone Mets Thread
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Bliss- The Rocky Mtn natl Park retreats are wonderful and they fill up fast. You can ride up to the top in the truck for the hut hikes if hiking is too much. I signed up for the Fowler Hilliard hut hike in September and may volunteer for another one. The woman who inspired Live by Living lived withstage IV for seven years after having had early stage 2B 19 years earlier.
A paper out today at ASCO indicated that adding fulvesant as second line therapy showed increased PFS for those with HER-. I will copy and paste and send it out tomorrow. Good stuff
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Meja, wow, you've really gone through an ordeal. You're probably still in a bit of shock over it, so allow yourself some time to process. And of course to heal physically. If your doctor is pleased, take some heart in that. There is no way around, over, or under scanxiety, you simply have to go through it. Think of what you've been through already. That same strength will get you through this next phase, too. Right now you don't have a plan, and the brain hates that. Once you get results, you will determine your plan and your brain will settle down. Sending you hugs of support.
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Meja - I am not sure anyone "manages" scan anxiety. We just get through it. The only thing I can say is that you have the strength to deal with any outcome, good or bad. You have a lot of treatment options. Stay with us and let us know.
>Z<
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Iwrite, Netta, MJH....thanks for your input. I've read that Fulvestrant is usually added if there's progression under Ibrance/Letrozole. I'm also on Xgeva. I'm on a trial for Ibrance/Letrozole but I've heard that there's another trial that includes Fulvestrant. I'm counting my chickens before they're hatched though as it's only an increase in pain in my active spots plus in a couple that haven't had pain for a long time so I'm not overly worried, I'm just the type who likes to have information at my fingertips. Once I have that information, I put my head down and live in the moment and take each day one at a time.
Meja....no wonder you have scanxiety but as Z says, it's just one of those things that we get through.
Lita...as always you make me feel awed. My problems are minuscule compared to where you are.
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Has anyone ever had a bone marrow biopsy? Mine is tomorrow at Ellis hospital in Schenectady NY. They are giving me conscious sedation..versed and fentanyl. Wonder about the advantages and disadvantages of that and what ur experiences may have been if you had it? The oncologist is looking for why my blood levels are still not returning to normal or close to normal when last dose of tchp chemo was December 18,2017? Currently still on herceptin. But nothing else. I'm 66, and lumpectomy showed need on Feb 6.really seeking any one of feedback
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Mybctc - I had a bone marrow biopsy with conscious sedation just a few weeks ago. The procedure, for me, was fairly easy. Good Luck tomorrow.
chrissy
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Mybctc, I had one back in March. Showed progression to bone marrow. Procedure itself was easy. I too had twilight sedation-versed and fentanyl. My rear end hurt for about a week after if I hit that spot just right. Taxol is slowly working. Oncologist trying to clear it with chemo but I’ve seen others on this board taking Ibrance and Letrozole. Good luck
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Chrissy50, what were the results of your bone marrow biopsy? Have you changed treatment?-Jill
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Someone mentioned FB groups similar to this group. Does anyone know the names of those FB pages
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laka - This group on FB 'Metastatic BC ibrance, kisqali, verzenio group (cdk4/6 inhibitor)' is for those taking the above meds for stage 4 - I am stage 4 bone mets too. Search it in FB , they will ask questions, then accept you.
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Laka....there are several FB groups for MBC. I've tried about five and found that a lot of members have a rather negative outlook. They didn't suit my purpose as there was nowhere near the amount of knowledge and information I gain on these boards but we're all different and you might find you fit in better than I did. I'm always a bit of a round peg in a square hole, I find. You can try out a lot of groups by searching "Explore Groups".
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Yesterday I asked aclinician from Lilly about the Abemaciclib fulvestrant combo as a potential second line for those who have been on Ibrance and letrozole. She said it showed good results in the first line but they haven't tested it as a second line treatment yet. ASCO had a good MBC video presentation yesterday that I'm trying to post...
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Well the breast cancer is back and I have extensive bone mets. No other organ involvement. Already received the first two faslodex shots, + Xgeva last week. I found out that I am eligible to receive a grant of $8000 for Ibrace. Haven't started that yet, pills coming today. I seemed to have handled the faslodex shots for the first 4-5 days. Not so sure now. Really have some major shortness of breath lately. Seems like a heavy pound on my chest. Don't know if normal or not. Anybody else have this? I see my onc tomorrow. Also having some sleep issues, don't seem to awaken fully refreshed. Thanks for your concern.
crissy
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Hello again!
Here is the link to the ASCO video on MBC from yesterday's plenary session. It compares recent trial results.
39,000 people in the cancer business attending this meeting and not one cure in sight. Had one young doctor stop by and tell me the "news" about ketogenic diets helping...really? :-(
Breast Cancer—Metastatic
Dr. Harold J. Burstein, Dana-Farber Cancer Institute0 -
Here is one of the abstracts...
Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: MONALEESA-3
Dennis J. Slamon, Patrick Neven, Stephen Chia, Peter A. Fasching, Michelino De Laurentiis, Seock-Ah Im...Show More
ABSTRACT
ChooseTop of pageAbstract <<INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCESPurpose
This phase III study evaluated ribociclib plus fulvestrant in patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer who were treatment naïve or had received up to one line of prior endocrine therapy in the advanced setting.
Patients and Methods
Patients were randomly assigned at a two-to-one ratio to ribociclib plus fulvestrant or placebo plus fulvestrant. The primary end point was locally assessed progression-free survival. Secondary end points included overall survival, overall response rate, and safety.
Results
A total of 484 postmenopausal women were randomly assigned to ribociclib plus fulvestrant, and 242 were assigned to placebo plus fulvestrant. Median progression-free survival was significantly improved with ribociclib plus fulvestrant versus placebo plus fulvestrant: 20.5 months (95% CI, 18.5 to 23.5 months) versus 12.8 months (95% CI, 10.9 to 16.3 months), respectively (hazard ratio, 0.593; 95% CI, 0.480 to 0.732; P < .001). Consistent treatment effects were observed in patients who were treatment naïve in the advanced setting (hazard ratio, 0.577; 95% CI, 0.415 to 0.802), as well as in patients who had received up to one line of prior endocrine therapy for advanced disease (hazard ratio, 0.565; 95% CI, 0.428 to 0.744). Among patients with measurable disease, the overall response rate was 40.9% for the ribociclib plus fulvestrant arm and 28.7% for placebo plus fulvestrant. Grade 3 adverse events reported in ≥ 10% of patients in either arm (ribociclib plus fulvestrant v placebo plus fulvestrant) were neutropenia (46.6% v 0%) and leukopenia (13.5% v 0%); the only grade 4 event reported in ≥ 5% of patients was neutropenia (6.8% v 0%).
Conclusion
Ribociclib plus fulvestrant might represent a new first- or second-line treatment option in hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer.
INTRODUCTIONChooseTop of pageAbstractINTRODUCTION <<PATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES
The cyclin D–cyclin-dependent kinase (CDK) 4/6–retinoblastoma pathway is frequently dysregulated in hormone receptor (HR) –positive breast cancer1and is implicated in resistance to endocrine monotherapy.2 Preclinical data indicate that CDK4/6-targeted agents inhibit HR-positive breast cancer cell-line growth and may act synergistically with hormonal blockade in this molecular subtype of the disease.3
Ribociclib is an orally bioavailable, highly selective small-molecule inhibitor of CDK4/6, with antitumor activity as a single agent and in combination with letrozole and fulvestrant in xenograft models of estrogen receptor–positive breast cancer.4,5 In the phase III MONALEESA-2 (Mammary ONcology Assessment of LEE011 [ribociclib] Efficacy and SAfety) study, ribociclib plus letrozole significantly prolonged progression-free survival (PFS) versus placebo plus letrozole in postmenopausal women with HR-positive/human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer who had received no prior therapy for advanced disease.6 Ribociclib and endocrine therapy combinations (tamoxifen or a nonsteroidal aromatase inhibitor and goserelin) also significantly improved PFS versus placebo plus endocrine therapy in premenopausal women with HR-positive/HER2-negative advanced breast cancer in the phase III MONALEESA-7 study.7
CDK4/6 inhibitors combined with fulvestrant have demonstrated efficacy in patients with HR-positive breast cancer who experienced progression during prior endocrine therapy.8-10 However, no study has evaluated ribociclib in combination with fulvestrant in HR-positive/HER2-negative advanced breast cancer or CDK4/6 inhibitor and fulvestrant combinations in patients with HR-positive/HER2-negative de novo advanced breast cancer or those who experienced relapse > 12 months after prior endocrine therapy.
Here, we present results from the MONALEESA-3 trial, which evaluated ribociclib plus fulvestrant in patients with HR-positive/HER2-negative advanced breast cancer who were treatment naïve in the advanced setting or had received up to one line of prior endocrine therapy for advanced disease.
PATIENTS AND METHODSChooseTop of pageAbstractINTRODUCTIONPATIENTS AND METHODS <<RESULTSDISCUSSIONREFERENCESStudy Design
In this phase III, double-blind, placebo-controlled international study, patients were randomly assigned at a two-to-one ratio to receive ribociclib (600 mg orally per day; 3 weeks on, 1 week off) plus fulvestrant (500 mg intramuscularly on day 1 of each 28-day cycle, with an additional dose on day 15 of cycle 1) or placebo plus fulvestrant. Random assignment was stratified by the presence or absence of lung or liver metastases (yes v no) and prior endocrine therapy (treatment naïve in the advanced setting v received up to one line of endocrine therapy for advanced disease, as described in Patients). Treatment continued until disease progression, unacceptable toxicity, death, or discontinuation for any other reason. Ribociclib dose modifications, including interruption and up to two dose reductions, were permitted to manage adverse events (AEs). Fulvestrant dose modifications were not allowed.
Written informed consent was obtained from all patients. The trial was conducted in accordance with the Good Clinical Practice guidelines and Declaration of Helsinki. The study protocol and any modifications were approved by an independent ethics committee or institutional review board at each site. A steering committee comprising participating international investigators and Novartis representatives oversaw the study conduct. An independent data monitoring committee assessed the safety data.
Patients
Postmenopausal women and men with histologically and/or cytologically confirmed HR-positive/HER2-negative advanced breast cancer were eligible. Patients were required to have advanced (metastatic or locoregionally recurrent disease not amenable to curative treatment) breast cancer. Additional eligibility criteria were as follows: (1) newly diagnosed (de novo), advanced breast cancer, (2) relapse > 12 months from completion of (neo)adjuvant endocrine therapy with no treatment for advanced or metastatic disease (criteria 1 and 2 referred to as treatment naïve in the advanced setting hereafter), (3) relapse on or within 12 months from completion of (neo)adjuvant endocrine therapy with no treatment for advanced or metastatic disease (early relapse), (4) relapse > 12 months from completion of (neo)adjuvant therapy with subsequent progression after one line of endocrine therapy for advanced or metastatic disease, and (5) advanced or metastatic breast cancer at diagnosis that progressed after one line of endocrine therapy for advanced disease with no prior (neo)adjuvant treatment for early disease (criteria 3 to 5 referred to as received up to one line of endocrine therapy for advanced disease hereafter). Criteria 1 and 2 includes patients receiving treatment in the first-line setting; criteria 3 to 5 includes patients receiving treatment in the second-line setting or with an early relapse.
Patients had at least one measurable lesion per Response Evaluation Criteria In Solid Tumors (RECIST; version 1.1)11 or one predominantly lytic bone lesion, with adequate organ and bone marrow function and an Eastern Cooperative Oncology Group performance status of 0 or 1.
Patients were ineligible if they had received prior treatment with chemotherapy for advanced disease, fulvestrant, or a CDK4/6 inhibitor; if they had inflammatory breast cancer, symptomatic visceral disease, or any disease burden that made the patient ineligible for endocrine therapy per investigator judgment; or if they had clinically significant cardiac arrhythmias and/or uncontrolled heart disease, including a QT interval corrected for heart rate according to Fridericia's formula (QTcF) > 450 ms.
Procedures
Tumor response was assessed locally per RECIST (version 1.1) at screening, every 8 weeks after random assignment for 18 months, and every 12 weeks thereafter until disease progression, death, withdrawal of consent, or loss to follow-up; for patients who discontinued for any other reason, assessments continued per protocol. Imaging data from approximately 40% of randomly selected patients were reviewed centrally by a blinded independent review committee (BIRC).
AEs were monitored and graded according to the Common Terminology Criteria for Adverse Events (version 4.03).12 Safety follow-up was conducted for at least 30 days after patients' last study treatment dose. ECG assessments were performed at screening, on day 15 of cycle 1, on days 1 and 15 of cycle 2, on day 1 of all subsequent cycles up to cycle 6, at end of treatment, and as clinically indicated. In patients with a QTcF ≥ 481 ms at any time before cycle 7, additional ECGs were performed predose on day 1 of subsequent cycles and postdose every third cycle.
Primary and Secondary End Points
The primary end point was locally assessed PFS. To support the primary end point, a BIRC performed a central assessment of PFS in a randomly selected subgroup of patients. Secondary end points included overall survival (OS), overall response rate (ORR), clinical benefit rate, and safety and tolerability.
Statistical Analysis
The primary analysis compared PFS between the treatment arms using a stratified log-rank test. The treatment effect was estimated using a Cox proportional hazards model overall and in relevant subgroups. The central PFS assessment used in support of the primary efficacy end point was analyzed using a Cox proportional hazards model. The primary PFS analysis was to be performed after observing approximately 364 local PFS events to detect a hazard ratio of 0.67 with 95% power and a one-sided 2.5% level of significance.
OS was compared between the treatment groups using a stratified log-rank test at a one-sided 2.5% level if the primary PFS end point was significant. A three-look design was used, with up to two OS interim analyses (the first was performed at the time of the PFS analysis) and a final OS analysis planned. The Lan-DeMets α-spending function with O'Brien-Fleming boundary was used to control for multiplicity. ORR and clinical benefit rate were compared between treatment arms using the Cochran-Mantel-Haenszel χ2 test at a one-sided 2.5% level.
All efficacy analyses were performed in the full analysis set, comprising all randomly assigned patients. Safety analyses were performed in patients who received at least one dose of any study treatment and had at least one postbaseline safety assessment.
RESULTSChooseTop of pageAbstractINTRODUCTIONPATIENTS AND METHODSRESULTS <<DISCUSSIONREFERENCESStudy Population and Disposition
Between June 2015 and June 2016, 726 patients from 177 study sites in 27 countries were randomly assigned at a two-to-one ratio to ribociclib plus fulvestrant (n = 484) or placebo plus fulvestrant (n = 242; Fig 1). Baseline demographics and disease characteristics were well balanced between arms (Table 1). Although male patients were eligible for enrollment after a protocol amendment, because of rapid recruitment, no male patients were enrolled. Median time from random assignment to data cutoff was 20.4 months. A total of 354 patients were treatment naïve for advanced disease, and 372 patients had received up to one line of prior endocrine therapy for advanced disease.
Fig 1.CONSORT diagram.
Table 1. Demographics and Baseline Characteristics
Table 1.Demographics and Baseline Characteristics
As of November 3, 2017, 42.1% of patients in the ribociclib plus fulvestrant arm versus 31.4% of patients in the placebo plus fulvestrant arm were still receiving treatment. The most common reasons for treatment discontinuation (ribociclib plus fulvestrant v placebo plus fulvestrant) were disease progression (39.9% v 58.7%) and AEs (8.5% v 4.1%).
Median duration of exposure to study treatment was 15.8 months (range, 0.9 to 27.4 months) for the ribociclib plus fulvestrant arm versus 12.0 months (range, 0.9 to 25.9 months) for the placebo plus fulvestrant arm. Median relative dose-intensity was 92.1% for ribociclib and 100% for placebo.
Primary End Point
At data cutoff, 210 PFS events had occurred in the ribociclib plus fulvestrant arm versus 151 in the placebo plus fulvestrant arm. PFS was significantly improved in the ribociclib plus fulvestrant arm versus the placebo plus fulvestrant arm, with a median PFS of 20.5 months (95% CI, 18.5 to 23.5 months) versus 12.8 months (95% CI, 10.9 to 16.3 months), respectively, and a hazard ratio of 0.593 (95% CI, 0.480 to 0.732; P < .001; Fig 2).
Fig 2.Kaplan-Meier analysis of locally assessed progression-free survival (PFS).
PFS analyses based on the BIRC were supportive of the primary efficacy results. In the 40% of randomly assigned patients (n = 290) included in the BIRC review, the PFS hazard ratio was 0.492 (95% CI, 0.345 to 0.703).
Exploratory analyses demonstrated consistent treatment effects across prespecified subgroups (Fig 3). The PFS hazard ratio was 0.577 (95% CI, 0.415 to 0.802) in patients who were treatment naïve in the advanced setting and 0.565 (95% CI, 0.428 to 0.744) in patients who had received up to one line of endocrine therapy for advanced disease. Due to a small sample size and limited number of events, the treatment effect hazard ratio in the Asian subgroup of patients should be interpreted with caution.
Fig 3.Progression-free survival outcomes in patient subgroups. Hazard ratios were estimated on the basis of stratified Cox proportional hazards model, except in subgroups related to stratification factors (presence or absence of lung or liver metastases and prior endocrine therapy), where an unstratified analysis was used. AI, aromatase inhibitor; ECOG PS, Eastern Cooperative Oncology Group performance status. (*) Prior endocrine therapy for advanced disease; 14 patients were not included in the prior endocrine therapy subgroup analysis because of missing data or criteria not being met.
Secondary End Points
At this first planned interim OS analysis, data were immature (34% information fraction). A total of 70 deaths (14.5%) were observed in the ribociclib plus fulvestrant arm versus 50 (20.7%) in the placebo plus fulvestrant arm, with results not crossing the prespecified O'Brien-Fleming stopping boundary.
ORR was 32.4% (95% CI, 28.3% to 36.6%) versus 21.5% (95% CI, 16.3% to 26.7%) for the ribociclib plus fulvestrant versus placebo plus fulvestrant arms, respectively, in all patients (P < .001; Table 2) and 40.9% (95% CI, 35.9% to 45.8%) versus 28.7% (95% CI, 22.1% to 35.3%), respectively, among patients with measurable disease at baseline (P = .003).
Table 2. Best Overall Response per Local Assessment in All Patients and in Patients With Measurable Disease
Table 2.Best Overall Response per Local Assessment in All Patients and in Patients With Measurable Disease
The safety population included 724 patients. The most common all-grade AEs reported in ≥ 30% of patients in either arm were neutropenia, nausea, and fatigue (Table 3). The most common grade 3 AEs occurring in ≥ 10% of patients were neutropenia and leukopenia. The only grade 4 event reported in ≥ 5% of patients was neutropenia. Febrile neutropenia occurred in 1.0% of patients in the ribociclib plus fulvestrant arm versus 0% of patients in the placebo plus fulvestrant arm.
Table 3. AEs Occurring in at Least 15% of Patients in Either Arm (safety population)
Table 3.AEs Occurring in at Least 15% of Patients in Either Arm (safety population)
AEs of ECG QT prolonged (any grade) occurred in 6.2% of patients receiving ribociclib plus fulvestrant and 0.8% of patients receiving placebo plus fulvestrant. Based on ECG assessments, a postbaseline QTcF > 480 ms occurred in 5.6% of patients in the ribociclib plus fulvestrant arm and 2.5% of patients in the placebo plus fulvestrant arm; of these, 1.7% and 0.4%, respectively, experienced a postbaseline QTcF interval > 500 ms. An increase of > 60 ms from baseline in the QTcF interval occurred in 6.5% and 0.4% of patients randomly assigned to ribociclib plus fulvestrant and placebo plus fulvestrant, respectively. Three patients (0.6%) in the ribociclib plus fulvestrant arm and no patient in the placebo plus fulvestrant arm discontinued study treatment because of a prolonged QTcF interval. There were no cases of torsades de pointes.
In the ribociclib plus fulvestrant arm, grade 3 or 4 elevated ALT occurred in 32 (6.6%) and nine patients (1.9%), respectively, and elevated AST in 23 (4.8%) and six patients (1.2%), respectively. In the placebo plus fulvestrant arm, grade 3 ALT and AST events occurred in one (0.4%) and two patients (0.8%), respectively, and there were no grade 4 elevated ALT or AST events. Two patients receiving ribociclib plus fulvestrant were confirmed cases of Hy's law; their liver enzymes returned to normal after discontinuation of ribociclib.
Serious AEs occurred in 138 (28.6%) and 40 patients (16.6%) in the ribociclib plus fulvestrant and placebo plus fulvestrant arms, respectively; of these, 54 (11.2%) and six (2.5%) were attributed to the study medication. The most common all-grade all-causality serious AEs reported in ≥ 1% of patients (ribociclib plus fulvestrant v placebo plus fulvestrant) were pneumonia (1.9% v 0%) and dyspnea (1.2% v 2.1%).
Ribociclib or placebo dose reductions were reported in 183 (37.9%) and 10 patients (4.1%) in the ribociclib plus fulvestrant and placebo plus fulvestrant arms, respectively; 148 (30.6%) and nine (3.7%) had a single dose reduction. AEs were the most common reason for dose reduction; 160 patients (33.1%) in the ribociclib plus fulvestrant arm had at least one dose reduction because of an AE versus eight (3.3%) in the placebo plus fulvestrant arm.
There were 13 deaths (2.7%) in the ribociclib plus fulvestrant arm and eight (3.3%) in the placebo plus fulvestrant arm during or within 30 days after treatment discontinuation; most resulted from disease progression (seven [1.4%] in the ribociclib plus fulvestrant arm v seven [2.9%] in the placebo plus fulvestrant arm). In the ribociclib plus fulvestrant arm, there was one death resulting from acute respiratory distress syndrome in a patient with baseline lung metastases, which was suspected to be related to study treatment. The remaining five deaths were unrelated to treatment and included cardiac failure, pneumonia, pulmonary embolism, hemorrhagic shock, and ventricular arrhythmia (one patient each). The patient with a ventricular arrhythmia had normal QTcF values while receiving treatment. After disease progression and treatment discontinuation, docetaxel plus capecitabine was initiated. The patient then developed a ventricular arrhythmia 17 days (more than five ribociclib half-lives; five half-lives is equivalent to 7 days) after the last ribociclib dose. The remaining death in the placebo plus fulvestrant arm resulted from a pulmonary embolism.
DISCUSSIONChooseTop of pageAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSION <<REFERENCES
The MONALEESA-3 study demonstrated that ribociclib plus fulvestrant significantly improves PFS compared with fulvestrant alone in postmenopausal women with HR-positive/HER2-negative advanced breast cancer, resulting in a 41% reduction in the risk of progression. To our knowledge, MONALEESA-3 is the first study to evaluate a CDK4/6 inhibitor–based combination with fulvestrant in patients who are treatment naïve in the advanced setting (ie, patients with de novo disease and those who experienced relapse > 12 months from completion of [neo]adjuvant endocrine therapy with no treatment for advanced disease). Median PFS for this subgroup was not reached for patients receiving ribociclib plus fulvestrant and was 18.3 months for those in the fulvestrant plus placebo arm, corresponding to a 42% reduction in the risk of progression. Ribociclib plus letrozole also demonstrated improved outcomes in patients who had received no prior therapy in the advanced setting, with a PFS hazard ratio of 0.568, compared with single-agent letrozole.13 These data provide additional confirmation of the use of ribociclib and endocrine therapy combinations, including fulvestrant, as effective first-line treatment for postmenopausal women with HR-positive/HER2-negative advanced breast cancer.
Patients who had received up to one line of prior endocrine therapy for advanced disease also derived benefit from ribociclib plus fulvestrant versus fulvestrant monotherapy, with a median PFS of 14.6 versus 9.1 months, respectively, and a 43% reduction in the risk of progression. In previous phase III studies, CDK4/6 inhibitor and fulvestrant combinations also prolonged PFS versus fulvestrant alone,8,10 confirming the clinical utility of these combinations in patients whose disease progressed during prior endocrine therapy.
OS results from MONALEESA-3 were not mature at the time of this analysis. They have yet to be reported for other CDK4/6 inhibitors in HR-positive/HER2-negative advanced breast cancer.
Similar to results from other ribociclib studies, ribociclib treatment effect was consistent across most prespecified subgroups, further supporting use of ribociclib-based therapy for a broad range of patients with HR-positive/HER2-negative advanced breast cancer.6,7 Although men were eligible for enrollment after a protocol amendment, no male patients were enrolled. Nevertheless, it remains conceivable that ribociclib plus fulvestrant may also provide benefit in male patients with HR-positive/HER2-negative advanced breast cancer.
The safety profile of ribociclib plus fulvestrant was consistent with that observed in other studies of ribociclib.6,7 Most AEs observed in the ribociclib plus fulvestrant arm were of mild or moderate severity, with no new safety signals observed. Although neutropenia was the most common all-grade and grade 3 or 4 AE, events were generally uncomplicated. AE-related treatment discontinuations were rare, further supporting the manageable safety profile of ribociclib-based combinations. The incidence of QTcF prolongation observed with ribociclib plus fulvestrant was similar to that previously reported with ribociclib,6,7 and there were no incidences of torsades de pointes. The frequency of elevated transaminases was higher in the ribociclib plus fulvestrant arm versus the placebo plus fulvestrant arm. However, the overall incidence of events was comparable to that observed in other studies of ribociclib.6,7 There were two patients in the ribociclib plus fulvestrant arm with cases of Hy's law, and in both patients, liver enzymes returned to normal after ribociclib discontinuation. Increased liver enzymes have also been observed in patients receiving fulvestrant monotherapy.14,15
Multiple studies have evaluated CDK4/6 inhibitor regimens in HR-positive/HER2-negative advanced breast cancer, and data from MONALEESA-3 provide additional confirmation of the efficacy and safety of ribociclib in this patient population. To the best of our knowledge, this is the first study to demonstrate that CDK4/6 inhibitor and fulvestrant combinations are efficacious in patients with de novo advanced breast cancer and in those who experienced relapse > 12 months after prior endocrine therapy. Additional analyses from the study may help further elucidate mechanisms of resistance to endocrine therapy and CDK4/6 inhibitors.
In conclusion, the MONALEESA-3 study demonstrates significantly improved PFS with ribociclib plus fulvestrant, with treatment benefit observed irrespective of prior endocrine therapy for advanced disease. Ribociclib and fulvestrant may represent a new therapeutic option in this subtype of advanced breast cancer, both for patients receiving treatment in the first-line setting (ie, treatment naïve for advanced breast cancer; including patients whose disease relapsed >12 months after completion of [neo]adjuvant therapy or patients with de novo advanced/metastatic disease [no prior exposure to endocrine therapy]) and for those receiving treatment in the second-line setting or who had an early relapse (ie, received up to one line of prior endocrine therapy in the advanced setting [early relapse defined as disease relapse on or ≤12 months since the completion of (neo)adjuvant endocrine therapy]). The efficacy results seen here for treatment-naïve advanced disease as well as those from other studies of CDK4/6 inhibitors in HR-positive/HER2-negative breast cancer support the study of ribociclib in early HR-positive/HER2-negative disease.
© 2018 by American Society of Clinical Oncology
Supported by Novartis Pharmaceuticals, which also funded medical writing assistance.
Processed as a Rapid Communication manuscript.
Clinical trial information: NCT02422615.
AUTHOR CONTRIBUTIONS
Conception and design: Dennis J. Slamon, Stephen Chia, Peter A. Fasching, Michelino De Laurentiis, Francisco J. Esteva, Miguel Martín, Xavier Pivot, Gena Vidam, Yingbo Wang, Karen Rodriguez Lorenc, Michelle Miller, Tetiana Taran, Guy Jerusalem
Provision of study materials or patients: Dennis J. Slamon, Patrick Neven, Stephen Chia, Peter A. Fasching, Michelino De Laurentiis, Seock-Ah Im, Katarina Petrakova, Giulia Val Bianchi, Francisco J. Esteva, Miguel Martín, Arnd Nusch, Gabe S. Sonke, Luis De La Cruz-Merino, J. Thaddeus Beck, Xavier Pivot, Guy Jerusalem
Collection and assembly of data: Gena Vidam, Yingbo Wang, Karen Rodriquez Lorenc, Michelle Miller, Tetiana Taran
Data analysis and interpretation: All authors
Manuscript writing: All authors
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Thank you lwrite. Processing.
Z
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That is alot to digest.
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Chrissy50-when i was first diagnosed with MBC, I also had extensive bone mets. I had pain in ribs and back, but also a very debiitating chest pressure and trouble breathing when I first stood up in the morning. Very uncomfortable...it completely resolved after one month on Ibrance/letrozole/Xgeva. Best, MJH
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Living between all the scans is one of the hardest parts of all this, but I try to keep the scanxiety in the back of my mind instead of letting it have a front row seat. If not, you are letting it tear you apart and take over your life. I personally like to view the scans for what they are, as helpful information and how we know what the crap is going on in there instead of wondering about it all the time. I get nervous about it, don't get me wrong, I've just made myself think of them positively. If it's a great scan, we jump for joy and live on cloud 9 until the next one, if it's a not good one, then I say, ok what do we do now to kick this thing in the ass. The way I see it, I am just a year out from my 1st dx and I'm planning on having 15+ more years of these crazy scans. So I better buckle up, put my earbuds in and try to relax on this long road trip. I know we are all different, and we all have to deal with this in our way. I am so thankful to all the courageous ladies on this site, I go to bed every night reading your posts. Puts a huge smile on my face knowing we all have each other's backs.
Jenn
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Kathryn, Thanks for reporting from ASCO2018!!! Shame on that guy for telling you to try ketogenic diets, what a crock and how patronizing!!
I saw this abstract as well, and Dennis Slamon is a genius, totally connected to the latest drugs, discoverer of HER2 and Ibrance (in the sense of being the first to test them in clinical trials, did not discover the drugs). I've met him a couple of times, he's a great guy.
This Ribociclib study tests the drug with Fulvestrant (Faslodex) as a first-line treatment and also as a second-line treatment after one round of prior endocrine therapy, but like all the other clinical trials done so far, the first-line would have been done without any Ibrance. So not directly relevant to us, but we can read between the lines a bit.
Because other data from ASCO 2018 indicates that mutations giving rise to resistance to Ibrance are only found in about 4-5% of the cases where progression happens on Ibrance-Femara (ie, 95% of the time it is because the cancer became resistant to the Femara, not the Ibrance), which means that for most of us, when we get progression on I-F, it is for the same reasons as people get progression on Femara alone. In that case, our results on subsequent treatment should be for the most part similar to what they get for secondline in this trial.
Quoting from your abstract, here are their results for secondline treatment:
Patients who had received up to one line of prior endocrine therapy for advanced disease also derived benefit from ribociclib plus fulvestrant versus fulvestrant monotherapy, with a median PFS of 14.6 versus 9.1 months, respectively, and a 43% reduction in the risk of progression. In previous phase III studies, CDK4/6 inhibitor and fulvestrant combinations also prolonged PFS versus fulvestrant alone, confirming the clinical utility of these combinations in patients whose disease progressed during prior endocrine therapy.
Conclusion: They got benefit to keeping on with the CDK4,6 inhibitors, for half of patients they got benefit for 14.6 months out of the combo treatment, and half went on even longer than that. And they cite that similar results were seen for Ibrance. So in principle, its a reasonable choice to move from Ibrance-Femara to Ibrance-Faslodex (or some other CDK4,6 inhibitor with Faslodex).
In principle, if they had a good PI3K inhibitor drug, it would be beneficial to throw that into the mix. But this is where we are. Thanks!
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Alwaysbepositive....I love that analogy: We're on a LONG road trip, not just a trip to the grocery store or the Post Office.
I've had so many MRIs, PETs, etc. that it really doesn't bother me that much anymore either. I figure, Mr. Cancer's gonna do whatever Mr. Cancer's gonna do. It's all between him and the LORD now. All I can do is keep going to my chemo infusions, take the meds they give me, try to eat a couple of decent meals a day, watch the sugars and salt, and leave it at that.
Take care, L
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good news girls after 3 weeks since my last blood tests tumour markers have dropped by 150 points . White blood cells are up hemoglobin still low but Doc thinks the new meds are reducing the cells in the bone marrow. I am glad I don't have to go down the chemo path atm. My tumour markers are so accurate that the dr will take notice of them first as scans seem to lag
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lwrite, I signed up for the park retreat in September, but haven't heard back yet, so I emailed. I just read about the woman who inspired Live by Living, and was an amazing story.
Thanks for posting all the ASCO info; lots to digest!
Delvzy, good to read of your positive results. Congrats.
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Delvzy, wonderful news. Go and celebrate your favorite way, be it bubble bath, glass of bubbly, or both!
Ah Chrissy, so sorry to hear about your progression, but you sound amazingly composed. I greatly admire that. I had sleep issues early on, some just from the sheer emotion, but also when I started Ibrance, with wild dreams that left me exhausted upon waking. So, could be your meds plus stress.
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Lita, once again great attitude I hope I can apply to myself. Chrissy sorry you joined the bone mets sisters. Dealing with some of my initial fears plus an Advil pm helped. I still have a few wakeful nights and crazy dreams but on the whole it’s better 13 months into mbc.0
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Jaylea & Maire - Since I have a treatment plan, IMO, somehow makes it easier to cope. I thought I did everything right 16 yrs ago when I was first DX'd. (IDC 2 centimeters, ER+ PR+ HER- no lymph no involvement. I had a lumpectomy 4 rounds of (the red devil) D & C then, taxotere along with 28 wks radiation.) Never in a million years did I think "IT" would return. But - it has. Now Round 2 for the second time dealing with treatment issues - Faslodex & Ibrace & Xgeva. I never reallly ask - why me? Why not me? When you look at all the odds of 1 in 8 of us will be diagnosed - not that great. I've come to realize the bad things happen to good people. All of us are examples of that. These boards 16 yrs ago gave me lots of comfort as they do now. There were only 3 forums at that time.
One day at a time, and hopefully that one day will be a good clear day!!!! One I'll wait for.
crissy
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When u take into consideration all cancers (pancreatic, lung, colon, skin, ovarian, prostate, kidney, lymphoma, soft tissue sarcoma, etc), we all have maybe a 1 in 4, or at best a 1 in 5, chance of getting one of them.
I've lost a half dozen friends in less than a year 2 various cancers...and that's not including bc at all.
L
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Hi from New Zealand.
I'm mostly a lurker around here, because I don't have much to offer, but today I need a bit of info. My history until now is below, but things have changed in the last couple of weeks, and not in a good way.
I have been off chemo since the beginning of April, and classed as almost stable, but my bone mets were very slow-growing and not causing any pain. In the past couple of weeks I have started to get dizzy spells, shortness of breath, and pains in all the bone met spots, as well as random stabs in my abdomen. I had my regular monthly Pamidronate / Aredia infusion on Thursday, with blood test before. It has come back that my platelets are WAY down, calcium WAY up, and my tumor marker (CA 15-3) has jumped from 29 to 296 in a month.
My tumor markers stayed at a consistent 11 for the first 2 years until my liver joined the party, so I'm assuming that the marker means my ascites have come back. My local Oncologist is organising a CT, and I will see my Med. Onc in 2 weeks. (The team comes from the Regional hospital 3 hours away once a month, and this was already booked).
My local Onc is saying that this may mean bone marrow involvement. Since I already know I have bone mets in both hips, pelvis, several ribs, at least 3 vertebrae and sternum, really how much difference will it make to treatment if it is in bone marrow? She said that they don't really want to do a biopsy unless they really have to, and from what I've read here, isn't exactly a fun experience.
The NZ health system means that I don't have to worry about cost (the majority of the system is completely free), and I have medical insurance to cover any un-funded drugs. New Zealand is way behind the rest of the world. eg. Ibrance won't be approved for funding here for another couple of years. I was diagnosed Stage 4 (bones only) de novo, so technically I have been terminal for 3 1/2 years. I am well aware I am on borrowed time, and am already hooked up with Hospice, Advanced Care plans etc, but this new development appears to be moving pretty fast, and I have no idea what will happen next.
Is it OK to go back for another go at the Taxol, since it seemed to work and the only side effect was hair loss? I finished 6 cycles, then moved on to 6 cycles of Xeloda, which was extended as a maintenance dose until Hand Foot Syndrome started up, along with diarrhea.
How different are bone marrow mets from "ordinary" bone mets? How differently are they treated? What chemo is used? Will they try radiation? Any info would be very much appreciated.
I'm trying not to panic too early, but 2 weeks is a long way off from where I am standing, I've gone from "pretty much normal" to 4 hour afternoon naps in a couple of weeks, and have stopped driving due to the dizzy spells. I think I'm sort of prepared for this to be the beginning of hte end, but it is still making me very nervous. Any suggestions would be very welcome.
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Someting I came across at the American Cancer Society web site:
"For adults, the most common bone cancer is chondrosarcoma, which has a 5-year relative survival of about 80%."
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Iwrite...thanks so much for all that invaluable information. I've copy pasted it to keep.
Alwaysbepositive.....your attitude is very much like mine regarding scans and this whole business. I'm more than a year and a half out from dx now and I must admit it does get a little bit harder with scans as time goes by, I've found. Just the same, I'm determined to keep that positive outlook and now allow them to get to me in between. In fact, I don't think about scans until an appointment is made. To be fair to a lot of the girls who have been through the wringer for years and years, with a lot of bad news meted out to them, I can understand why they would be concerned at another scan coming up. Thanks for your great post and reminder to all of us to remember that positivity pays off in quality of life.
Chrissy50....so sorry to hear of your progression.
Cure-ious...thanks for your analysis. It was very helpful.
Delvzy....great news!
suems....I can't give you much by way of information. There will be other with a lot more knowledge than I have, but I can send you love and support. The only thing I will say (and I'd like confirmation of this from others) is that my understanding of terminal means that all treatment options have been exhausted. Have you ever been told that? Because, although procuring Ibrance isn't possible unless you have a way of obtaining it from overseas, surely there must be another chemo that can be tried? I apologise if I'm wrong about this but I've looked at the string of chemotherapy drugs you've had to endure and I know that there are some others which are new. I can understand why you're feeling so nervous. I certainly would be too, but don't give up and think of this as the beginning of the end unless your Med Onc tells you there are no more treatment options for you. Sending you love, light and lots of warm hugs.
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