Itovebi Drug Information
Generic name: INAVOLISIB
Kinase Inhibitor [EPC]
Uses of Itovebi
ITOVEBI, in combination with palbociclib and fulvestrant, is indicated for the treatment of adults with endocrine-resistant, PIK3CA -mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after completing adjuvant endocrine therapy.
Dosage & Administration of Itovebi
Patient Selection
Select patients for the treatment of HR-positive, HER2-negative, locally advanced or metastatic breast cancer with ITOVEBI based on the presence of one or more PIK3CA mutations in plasma specimens. Information on FDA-approved tests for the detection of PIK3CA mutations in breast cancer is available at: http://www.fda.gov/companiondiagnostics.
Recommended Evaluation Before Initiating ITOVEBI
Evaluate fasting plasma glucose (FPG)/blood glucose (FBG) and hemoglobin A 1C (HbA 1C ) and optimize blood glucose prior to starting ITOVEBI and at regular intervals during treatment.
Recommended Dosage
The recommended dosage of ITOVEBI is 9 mg taken orally once daily, with or without food, until disease progression or unacceptable toxicity. Advise patients to take ITOVEBI at approximately the same time each day. Swallow ITOVEBI tablet(s) whole.
Do not chew, crush, or split prior to swallowing. If a patient misses a dose, instruct the patient to take the missed dose as soon as possible within 9 hours. After more than 9 hours, instruct the patient to skip the dose and take the next dose at the scheduled time.
If a patient vomits a dose, instruct patients not to take an additional dose on that day and resume the usual dosing schedule the next day. Administer ITOVEBI in combination with palbociclib and fulvestrant. Refer to the Full Prescribing Information for palbociclib and fulvestrant for dosing information.
For premenopausal and perimenopausal women, administer a luteinizing hormone-releasing hormone (LHRH) agonist in accordance with local clinical practice. For men, consider administering an LHRH agonist in accordance with local clinical practice.
Dosage Modifications for Adverse Reactions
The recommended dose reduction levels of ITOVEBI for adverse reactions are listed in Table 1. Permanently discontinue ITOVEBI if patients are unable to tolerate the second dose reduction. Table 1: Dose Reduction for The recommended dosage modifications of ITOVEBI for adverse reactions are summarized in Table 2.
Table 2: Recommended Dosage Modifications for Adverse Reactions Adverse Reaction Severity Dosage Modification Hyperglycemia Before initiating treatment with ITOVEBI, test FPG or FBG, and HbA 1C levels, and optimize plasma/blood glucose levels in all patients. After initiating treatment with ITOVEBI, monitor FPG or FBG levels based on the recommended schedule, and as clinically indicated.
Recommended Dosage in Patients with Moderate or Severe Renal Impairment The recommended dosage of ITOVEBI for patients with moderate renal impairment (eGFR 30 to < 60 mL/min based on CKD-EPI) is 6 mg orally once daily.
| Dose Level | Dose and Schedule |
|---|---|
| Recommended starting dose | 9 mg daily |
| First dose reduction | 6 mg daily |
| Second dose reduction | 3 mg daily |
| Adverse Reaction | Severity | Dosage Modification |
|---|---|---|
| Hyperglycemia Before initiating treatment with ITOVEBI, test FPG or FBG, and HbA 1C levels, and optimize plasma/blood glucose levels in all patients. After initiating treatment with ITOVEBI, monitor FPG or FBG levels based on the recommended schedule, and as clinically indicated [see Warnings and Precautions (5.1) ]. [see Warnings and Precautions (5.1) ] | Fasting glucose levels (FPG or FBG) > ULN to 160 mg/dL (> ULN – 8.9 mmol/L) | No adjustment of ITOVEBI required. Consider dietary modifications and ensure adequate hydration. Initiate or intensify oral anti-hyperglycemic medications for patients with risk factors for hyperglycemia. |
| Fasting glucose levels > 160 to 250 mg/dL (> 8.9 – 13.9 mmol/L) | Withhold ITOVEBI until FPG or FBG ≤ 160 mg/dL (≤ 8.9 mmol/L). Initiate or intensify anti-hyperglycemic medications. Resume ITOVEBI at the same dose level. If FPG or FBG persists > 200 – 250 mg/dL (> 11.1 – 13.9 mmol/L) for 7 days under appropriate anti-hyperglycemic treatment, consider consultation with a healthcare professional experienced in the treatment of hyperglycemia. | |
| Fasting glucose levels > 250 to 500 mg/dL (> 13.9 – 27.8 mmol/L) | Withhold ITOVEBI. Initiate or intensify anti-hyperglycemic medications. Administer appropriate hydration if required. If FPG or FBG decreases to ≤ 160 mg/dL (≤ 8.9 mmol/L) within 7 days, resume ITOVEBI at the same dose level. If FPG or FBG decreases to ≤ 160 mg/dL (≤ 8.9 mmol/L) in ≥ 8 days, resume ITOVEBI at one lower dose level. If FPG or FBG > 250 to 500 mg/dL (> 13.9 – 27.8 mmol/L) recurs within 30 days, withhold ITOVEBI until FPG or FBG decreases to ≤ 160 mg/dL (≤ 8.9 mmol/L). Resume ITOVEBI at one lower dose level. | |
| Fasting glucose levels > 500 mg/dL (> 27.8 mmol/L) | Withhold ITOVEBI. Initiate or intensify anti-hyperglycemic medications. Assess for volume depletion and ketosis and administer appropriate hydration. If FPG or FBG decreases to ≤ 160 mg/dL (≤ 8.9 mmol/L), resume ITOVEBI at one lower dose level. If FPG or FBG > 500 mg/dL (> 27.8 mmol/L) recurs within 30 days, permanently discontinue ITOVEBI. | |
| Stomatitis [see Warnings and Precautions (5.2) ] | Grade 1 Based on CTCAE version 5.0. | No adjustment of ITOVEBI required. Initiate or intensify appropriate medical therapy (e.g., corticosteroid-containing mouthwash) as clinically indicated. |
| Grade 2 | Withhold ITOVEBI until recovery to Grade ≤ 1. Initiate or intensify appropriate medical therapy. Resume ITOVEBI at the same dose level. For recurrent Grade 2 stomatitis, withhold ITOVEBI until recovery to Grade ≤ 1, then resume ITOVEBI at one lower dose level. | |
| Grade 3 | Withhold ITOVEBI until recovery to Grade ≤ 1. Initiate or intensify appropriate medical therapy. Resume ITOVEBI at one lower dose level. | |
| Grade 4 | Permanently discontinue ITOVEBI. | |
| Diarrhea [see Warnings and Precautions (5.3) ] | Grade 1 | No adjustment of ITOVEBI required. Initiate appropriate medical therapy and monitor as clinically indicated. |
| Grade 2 | Withhold ITOVEBI until recovery to Grade ≤ 1, then resume ITOVEBI at the same dose level. Initiate or intensify appropriate medical therapy and monitor as clinically indicated. For recurrent Grade 2 diarrhea, withhold ITOVEBI until recovery to Grade ≤ 1, then resume ITOVEBI at one lower dose level. | |
| Grade 3 | Withhold ITOVEBI until recovery to Grade ≤ 1, then resume ITOVEBI at one lower dose level. Initiate or intensify appropriate medical therapy and monitor as clinically indicated. | |
| Grade 4 | Permanently discontinue ITOVEBI. | |
| Hematologic Toxicities [see Adverse Reactions (6.1) ] | Grade 1, 2, or 3 | No adjustment of ITOVEBI required. Monitor complete blood count and for signs or symptoms of hematologic toxicities as clinically indicated. |
| Grade 4 | Withhold ITOVEBI until recovery to Grade ≤ 2. Resume ITOVEBI at the same dose level or reduce to one lower dose level as clinically indicated. | |
| Other Adverse Reactions [see Adverse Reactions (6.1) ] | Grade 1 | No adjustment of ITOVEBI required. |
| Grade 2 | Consider withholding ITOVEBI, if clinically indicated, until recovery to Grade ≤ 1. Resume ITOVEBI at the same dose level. | |
| Grade 3 (first event) | Withhold ITOVEBI until recovery to Grade ≤ 1. Resume ITOVEBI at the same dose level or one lower dose level based on clinical evaluation. | |
| Grade 3 (recurrent) | Withhold ITOVEBI until recovery to Grade ≤ 1. Resume ITOVEBI at one lower dose level. | |
| Grade 4 | Permanently discontinue ITOVEBI. |
Side Effects of Itovebi
Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Locally Advanced or Metastatic Breast Cancer INAVO120 The safety of ITOVEBI was evaluated in a randomized, double-blind, placebo-controlled study (INAVO120) in 324 patients with PIK3CA -mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer. Patients received either ITOVEBI 9 mg (n=162) or placebo (n=162) with palbociclib and fulvestrant.
The median duration of treatment with ITOVEBI was 9 months (range: 0 to 39 months) in the ITOVEBI with palbociclib and fulvestrant arm. Serious adverse reactions occurred in 24% of patients who received ITOVEBI with palbociclib and fulvestrant. Fatal adverse reactions occurred in 3.7% of patients who received ITOVEBI with palbociclib and fulvestrant, including (0.6% each) acute coronary syndrome, cerebral hemorrhage, cerebrovascular accident, COVID-19 infection, and gastrointestinal hemorrhage.
Permanent discontinuation of ITOVEBI due to an adverse reaction occurred in 6% of patients. Adverse reactions which resulted in permanent discontinuation of ITOVEBI included hyperglycemia (1.2%), and (0.6% each) stomatitis, gastric ulcer, intestinal perforation, anal abscess, increased ALT, decreased weight, bone pain, musculoskeletal pain, transitional cell carcinoma, and acute kidney injury. Dosage interruptions of ITOVEBI due to an adverse reaction occurred in 69% of patients.
Dose reductions of ITOVEBI due to adverse reactions occurred in 14% of patients. Adverse reactions which required dose reduction of ITOVEBI in ≥ 2% of patients were stomatitis (3.7%) and hyperglycemia (2.5%). The most common (≥ 20%) adverse reactions, including laboratory abnormalities, were decreased neutrophils, decreased hemoglobin, increased fasting glucose, decreased platelets, decreased lymphocytes, stomatitis, diarrhea, decreased calcium, fatigue, decreased potassium, increased creatinine, increased ALT, nausea, decreased sodium, decreased magnesium, rash, decreased appetite, COVID-19 infection, and headache.
Adverse reactions and laboratory abnormalities in INAVO120 are summarized in Table 3 and Table 4, respectively. Patient-reported symptoms are summarized in Table 5. Table 4: Select Laboratory Abnormalities (≥ 10% with a ≥ 2% Higher Incidence in the ITOVEBI Arm) in INAVO, patient-reported symptomatic toxicities (i.e., diarrhea, nausea, vomiting, fatigue, mouth sores, decreased appetite, and rash) were assessed via the Patient-Reported Outcomes – Common Terminology Criteria for Adverse Events (PRO-CTCAE) at baseline, every two weeks through Cycle 3 Day 15, and then Day 1 of every other 28-day cycle until treatment discontinuation.
Completion rates in both arms were > 90% at baseline and > 80% at subsequent time points where > 50% of randomized patients were on treatment. Table 5: Patient-Reported Symptoms Assessed by PRO-CTCAE in INAVO Patient-reported overall side-effect impact was assessed using the Modified Bother Item (MBI). Patients provided a response to "I am bothered by side effects of treatment," and at baseline the proportion of patients with MBI responses of "not at all" were 70% in the ITOVEBI with palbociclib and fulvestrant arm and 76% in the placebo with palbociclib and fulvestrant arm.
At Cycle 2 Day 15, the proportion of patients with MBI responses of "not at all" were 25% in the ITOVEBI with palbociclib and fulvestrant arm and 53% in the placebo with palbociclib and fulvestrant arm. Through 31 cycles of treatment, patients in the ITOVEBI with palbociclib and fulvestrant arm reported more side effect bother compared to the placebo with palbociclib and fulvestrant arm.
Postmarketing Experience
The following adverse reactions have been identified during post-approval use of ITOVEBI. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Metabolism and Nutrition Disorders: Ketoacidosis
| Adverse Reaction | ITOVEBI + Palbociclib + Fulvestrant N=162 | Placebo + Palbociclib + Fulvestrant N=162 | ||
|---|---|---|---|---|
| All Grades (%) | Grade 3-4 (%) | All Grades (%) | Grade 3-4 (%) | |
| Gastrointestinal Disorders | ||||
| Stomatitis Includes aphthous ulcer, glossitis, glossodynia, lip ulceration, mouth ulceration, mucosal inflammation, and stomatitis. | 51 | 6 No Grade 4 adverse reactions were observed. | 27 | 0 |
| Diarrhea | 48 | 3.7 | 16 | 0 |
| Nausea | 28 | 0.6 | 17 | 0 |
| Vomiting | 15 | 0.6 | 5 | 1.2 |
| General Disorders and Administration Site Conditions | ||||
| Fatigue | 38 | 1.9 | 25 | 1.2 |
| Skin and Subcutaneous Tissue Disorders | ||||
| Rash Includes other related terms. | 26 | 0 | 19 | 0 |
| Alopecia | 19 | 0 | 6 | 0 |
| Dry skin Includes dry skin, skin fissures, xerosis, and xeroderma. | 13 | 0 | 4.3 | 0 |
| Metabolism and Nutrition Disorders | ||||
| Decreased appetite | 24 | 0 | 9 | 0 |
| Infections and Infestations | ||||
| COVID-19 infection | 23 | 1.9 | 11 | 0.6 |
| Urinary tract infection | 15 | 1.2 | 9 | 0 |
| Nervous System Disorders | ||||
| Headache | 22 | 0 | 14 | 0 |
| Investigations | ||||
| Decreased weight | 17 | 3.7 | 0.6 | 0 |
| Laboratory Abnormality | ITOVEBI + Palbociclib + Fulvestrant The denominator used to calculate the rate varied from 122 to 160 based on the number of patients with a baseline value and at least one post-treatment value. | Placebo + Palbociclib + Fulvestrant The denominator used to calculate the rate varied from 131 to 161 based on the number of patients with a baseline value and at least one post-treatment value. | ||
|---|---|---|---|---|
| All Grades (%) | Grade 3-4 (%) | All Grades (%) | Grade 3-4 (%) | |
| ALT = alanine aminotransferase | ||||
| Hematology | ||||
| Neutrophils (total, absolute) decreased | 95 | 82 | 97 | 79 |
| Hemoglobin decreased | 88 | 8 No Grade 4 laboratory abnormalities were observed. | 85 | 2.5 |
| Platelets decreased | 84 | 16 | 71 | 3.7 |
| Lymphocytes (absolute) decreased | 72 | 9 | 68 | 14 |
| Chemistry | ||||
| Glucose (fasting) increased Grading according to CTCAE version 4.03. | 85 | 12 | 43 | 0 |
| Calcium decreased | 42 | 3.1 | 32 | 3.7 |
| Potassium decreased | 38 | 6 | 21 | 0.6 |
| Creatinine increased | 38 | 1.9 | 30 | 1.2 |
| ALT increased | 34 | 3.1 | 29 | 1.2 |
| Sodium decreased | 28 | 2.5 | 19 | 2.5 |
| Magnesium decreased | 27 | 0.6 | 21 | 0 |
| Lipase (fasting) increased | 16 | 1.4 | 7 | 0 |
| ITOVEBI+P+F = ITOVEBI with palbociclib and fulvestrant arm; Placebo+P+F = placebo with palbociclib and fulvestrant arm. | ||||||||
| Symptom (Attribute) The symptom attribute scoring is defined by amount/frequency/severity with a score of 0 = 'not at all'/'never'/'none'; 1 = 'a little bit'/'rarely'/'mild'; 2 = 'somewhat'/'occasionally'/'moderate'; 3 = 'quite a bit'/'frequently'/'severe'; 4 = 'very much'/'almost constantly'/'very severe'. | Any Symptom Before Treatment (%) The percentage of patients whose symptom score before treatment was 1-4. | Any Worsening on Treatment (%) The percentage of patients whose symptom score increased during treatment, with respect to their score before treatment. | Worsening to Score 3 or 4 (%) The percentage of patients whose symptom score increased to 3 or 4 during treatment, with respect to their score before treatment. | |||||
| ITOVEBI + P + F (N=148) The number of patients who provided a score before treatment and at least one on-treatment score. | Placebo + P + F (N=152) | ITOVEBI + P + F (N=148) | Placebo + P + F (N=152) | ITOVEBI + P + F (N=148) | Placebo + P + F (N=152) | |||
| Diarrhea (frequency), % | 23 | 15 | 78 | 49 | 32 | 8 | ||
| Nausea (frequency), % | 21 | 21 | 59 | 50 | 20 | 11 | ||
| Vomiting (frequency), % | 9 | 6 | 35 | 26 | 6 | 3.3 | ||
| Fatigue (severity), % | 72 | 69 | 72 | 58 | 32 | 22 | ||
| Mouth sores (severity), % | 11 | 14 | 74 | 52 | 30 | 9 | ||
| Decreased appetite (severity), % | 38 | 28 | 78 | 55 | 26 | 12 | ||
| Symptom (Attribute) | Baseline Presence | Post-baseline Presence | ||||||
| ITOVEBI + P + F (N=148) | Placebo + P + F (N=152) | ITOVEBI + P + F (N=148) | Placebo + P + F (N=152) | |||||
| Rash (yes), % | 5 | 5 | 50 | 38 | ||||
Warnings & Cautions for Itovebi
Hyperglycemia Severe or fatal hyperglycemia, including ketoacidosis, can occur in patients treated with ITOVEBI. Ketoacidosis with a fatal outcome has occurred in the postmarketing setting. Among patients with hyperglycemia, the median time to first onset was 7 days (range: 2 to 955 days).
Hyperglycemia led to dose interruption in 28%, to dose reduction in 2.5%, and to discontinuation of ITOVEBI in 1.2% of patients. The safety of ITOVEBI in patients with Type 1 diabetes mellitus, or Type 2 diabetes mellitus requiring ongoing anti-hyperglycemic treatment have not been studied. Before initiating treatment with ITOVEBI, test fasting glucose levels (FPG or FBG), HbA 1C levels, and optimize fasting glucose.
Monitor HbA 1C every 3 months and as clinically indicated. Manage hyperglycemia with anti-hyperglycemic medications as clinically indicated. During treatment with anti-hyperglycemic medication, continue monitoring fasting glucose levels.
Patients with a history of well-controlled Type 2 diabetes mellitus may require intensified anti-hyperglycemic treatment and close monitoring of fasting glucose levels. Consider consultation with a healthcare professional experienced in the treatment of hyperglycemia, and initiation of fasting glucose monitoring at home for patients who have risk factors for hyperglycemia or who experience hyperglycemia. Advise patients of the signs and symptoms of hyperglycemia and counsel patients on lifestyle changes.
Based on the severity of the hyperglycemia, ITOVEBI may require dose interruption, reduction, or discontinuation.
Stomatitis
Severe stomatitis can occur in patients treated with ITOVEBI. Stomatitis occurred in 51% of patients treated with ITOVEBI in combination with palbociclib and fulvestrant, including Grade 3 events in 6% of patients. The median time to first onset was 13 days (range: 1 to 610 days).
Stomatitis led to dose interruption in 10%, to dose reduction in 3.7%, and to discontinuation of ITOVEBI in 0.6% of patients. In patients who received ITOVEBI in combination with palbociclib and fulvestrant, 38% used a mouthwash containing corticosteroid for management or prophylaxis of stomatitis. Monitor patients for signs and symptoms of stomatitis.
Withhold, reduce dose, or permanently discontinue ITOVEBI based on severity.
Diarrhea
Severe diarrhea, including dehydration and acute kidney injury, can occur in patients treated with ITOVEBI. Diarrhea occurred in 48% of patients treated with ITOVEBI in combination with palbociclib and fulvestrant, including Grade 3 events in 3.7% of patients. The median time to first onset was 15 days (range: 2 to 602 days).
Diarrhea led to dose interruptions in 7% of patients, and dose reductions in 1.2% of patients. Anti-diarrheal medicines were used in 28% (46/162) of patients who received ITOVEBI in combination with palbociclib and fulvestrant to manage symptoms. Monitor patients for signs and symptoms of diarrhea.
Advise patients to increase oral fluids and start anti-diarrheal treatment at the first sign of diarrhea while taking ITOVEBI.
Embryo-Fetal Toxicity Based on findings in animals and its mechanism of action, ITOVEBI can cause fetal harm when administered to a pregnant woman. In an animal reproduction study, oral administration of inavolisib to pregnant rats during the period of organogenesis caused adverse developmental outcomes, including embryo-fetal mortality, structural abnormalities, and alterations to growth at maternal exposures approximately equivalent to the human exposure at the recommended dose of 9 mg/day based on area under the curve (AUC). Advise pregnant women and females of reproductive potential of the potential risk to a fetus.
Advise females of reproductive potential to use effective non-hormonal contraception during treatment with ITOVEBI and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ITOVEBI and for 1 week after the last dose. ITOVEBI is used in combination with palbociclib and fulvestrant.
Refer to the Full Prescribing Information of palbociclib and fulvestrant for pregnancy and contraception information.
Pregnancy Safety for Itovebi
Pregnancy Risk Summary ITOVEBI is used in combination with palbociclib and fulvestrant. Refer to the Full Prescribing Information of palbociclib and fulvestrant for pregnancy information. Based on animal data and its mechanism of action, ITOVEBI can cause fetal harm when administered to a pregnant woman.
There are no available data on the use of ITOVEBI in pregnant women to inform a drug-associated risk. In an animal reproduction study, oral administration of inavolisib to pregnant rats during the period of organogenesis caused adverse developmental outcomes, including embryo-fetal mortality, structural abnormalities, and alterations to growth at maternal exposures approximately equivalent to the human exposure at the recommended dose of 9 mg/day based on AUC (see Data ). Advise pregnant women and females of reproductive potential of the potential risk to a fetus.
The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data In an embryo-fetal development study, pregnant rats received oral doses of inavolisib up to 6 mg/kg/day during the period of organogenesis. Administration of doses ≥ 2 mg/kg/day resulted in decreases in fetal body weight and placental weight, post-implantation loss, lower fetal viability, fetal malformations (including kyphosis of vertebral column, fused thoracic arch, microphthalmia) and variations (including dilated renal pelvis, short supernumerary rib, wavy rib).
At a dose of 2 mg/kg/day, maternal exposures were 0.9 times the human exposure at the recommended dose of 9 mg/day based on AUC.
Pediatric Use of Itovebi
Pediatric Use The safety and efficacy of ITOVEBI in pediatric patients have not been established.
Clinical Studies of Itovebi
Locally Advanced or Metastatic Breast Cancer INAVO120 INAVO120 (NCT04191499) was a randomized (1:1), double-blind, placebo-controlled trial evaluating the efficacy of ITOVEBI in combination with palbociclib and fulvestrant in adult patients with endocrine-resistant PIK3CA -mutated, HR-positive, HER2-negative (defined as IHC 0 or 1+, or IHC 2+/ISH-), locally advanced or metastatic breast cancer whose disease progressed during or within 12 months of completing adjuvant endocrine therapy and who have not received prior systemic therapy for locally advanced or metastatic disease. Randomization was stratified by presence of visceral disease (yes or no), endocrine resistance (primary or secondary), and geographic region (North America/Western Europe, Asia, other). Primary endocrine resistance was defined as relapse while on the first 2 years of adjuvant endocrine therapy (ET) and secondary endocrine resistance was defined as relapse while on adjuvant ET after at least 2 years or relapse within 12 months of completing adjuvant ET.
Patients were required to have HbA 1C < 6% and fasting blood glucose < 126 mg/dL. The study excluded patients with Type 1 diabetes mellitus or Type 2 diabetes mellitus requiring ongoing anti-hyperglycemic treatment at the start of study treatment. PIK3CA mutation status was prospectively determined in a central laboratory using the FoundationOne ® Liquid CDx assay on plasma-derived circulating tumor DNA (ctDNA) or in local laboratories using various validated polymerase chain reaction (PCR) or next-generation sequencing (NGS) assays on tumor tissue or plasma.
All patients were required to provide both a freshly collected pre-treatment blood sample and a tumor tissue sample for central evaluation and determination of PIK3CA mutation(s) status. Patients received treatment until disease progression or unacceptable toxicity. In addition, all pre/perimenopausal women and men received an LHRH agonist throughout therapy.
Tamoxifen (57%) and aromatase inhibitors (50%) were the most commonly used adjuvant endocrine therapies. Sixty-four percent of patients were considered to have secondary endocrine resistance. Eighty-three percent of patients had received prior chemotherapy (in the neo/adjuvant setting) and 1.2% of patients had been treated with a CDK4/6 inhibitor.
The major efficacy outcome measure was investigator (INV)-assessed progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Additional efficacy outcome measures included overall survival (OS), INV-assessed objective response rate (ORR), and INV-assessed duration of response (DOR). Efficacy results are summarized in Table 6, Figure 1, and Figure 2.
INV-assessed PFS results were supported by consistent results from a blinded independent central review (BICR) assessment.
| Efficacy Endpoint | ITOVEBI + Palbociclib + Fulvestrant N=161 | Placebo + Palbociclib + Fulvestrant N=164 |
|---|---|---|
| CI = confidence interval; CR = complete response; DOR = duration of response; PR = partial response | ||
| Progression-Free Survival Per RECIST version 1.1., Based on investigator assessment., Results at the pre-specified final PFS analysis. | ||
| Patients with event, n (%) | 82 (51) | 113 (69) |
| Median, months (95% CI) | 15.0 (11.3, 20.5) | 7.3 (5.6, 9.3) |
| Hazard ratio (95% CI) Based on a stratified Cox regression model. | 0.43 (0.32, 0.59) | |
| p-value Based on a stratified log-rank test. | < 0.0001 | |
| Overall Survival Results at the pre-specified final overall survival analysis., The prespecified boundary for statistical significance was p < 0.0469. | ||
| Patients with event, n (%) | 72 (45) | 82 (50) |
| Median, months (95% CI) | 34 (28.4, 44.8) | 27 (22.8, 38.7) |
| Hazard ratio (95% CI) | 0.67 (0.48, 0.94) | |
| p-value | 0.0190 | |
| Objective Response Rate,,, Based on confirmed ORR. | ||
| Patients with CR or PR, n (%) | 94 (58) | 41 (25) |
| 95% CI | (50, 66) | (19, 32) |
| p-value Based on a stratified Cochran-Mantel-Haenszel test. | < 0.0001 | |
| Duration of Response,, | ||
| Median DOR, months (95% CI) | 18.4 (10.4, 22.2) | 9.6 (7.4, 16.6) |
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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