When PSA is rising despite GnRH therapy, when should patients like Walter be scanned for metastases?

Patient Profile, Walter

Walter H, 68 years old

Diagnosed with prostate cancer 7 years ago

Not an actual patient or patient case; content for illustrative purposes only.

Prostate Cancer Progression Graph, Walter
INITIAL PRESENTATION:Diagnosis
PSA
10.3 ng/mL

Gleason score: 7 (4+3)

Scans detect no metastases*

Treatment: Radical prostatectomy

3 months
PSA undetectable
3 months post-radical prostatectomy
PROGRESSION:5 years 3 months
Confirmed PSA
0.6 ng/mL

Treatment:
Began GnRH therapy

5 years 9 months
PSAReached nadir to
0.2 ng/mL
6 months after GnRH therapy initiation
7 years Steadily rising for a year
Confirmed PSA
2.4 ng/mL

Current prostate cancer therapy: GnRH therapy Scans detect no metastases*

21 months after GnRH therapy initiation

Notes:

  • Is generally healthy; can do the things he did before he was diagnosed with prostate cancer
  • Asymptomatic, no pain present
  • Has mild hypertension
  • Continue monitoring
CRPC, castration-resistant prostate cancer; CT, computed tomography; GnRH therapy, gonadotropin-releasing hormone therapy; PSA, prostate-specific antigen; 99mTc, technetium-99. *99mTc bone scintigraphy and abdomen/pelvis/chest CT.

CRPC, castration-resistant prostate cancer; CT, computed tomography; GnRH therapy, gonadotropin-releasing hormone therapy; PSA, prostate-specific antigen; 99mTc, technetium-99.

*99mTc bone scintigraphy and abdomen/pelvis/chest CT.

Imaging recommendations from a multidisciplinary group of urologists, radiologists, and oncologists—the Radiographic Assessments for Detection of Advanced Recurrence (RADAR) Group—may help guide your treatment decisions for patients like Walter.
RADAR imaging recommendations for patients with nonmetastatic CRPC1
  • FIRST SCAN when PSA ≥ 2 ng/mL
  • If negative, SECOND SCAN when PSA = 5 ng/mL
  • If negative, ADDITONAL SCANS whenever PSA doubles

Indication

XTANDI (enzalutamide) capsules is indicated for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC).

Important Safety Information

Contraindications
XTANDI is not indicated for women. XTANDI can cause fetal harm and potential loss of pregnancy.

Warnings and Precautions
Seizure occurred in 0.5% of patients receiving XTANDI in clinical studies. In a study of patients with predisposing factors, seizures were reported in 2.2% of patients. See section 5.1 of the Prescribing Information for the list of predisposing factors. It is unknown whether anti-epileptic medications will prevent seizures with XTANDI. Permanently discontinue XTANDI in patients who develop a seizure during treatment.

Posterior Reversible Encephalopathy Syndrome (PRES)  In post approval use, there have been reports of PRES in patients receiving XTANDI. PRES is a neurological disorder which can present with rapidly evolving symptoms including seizure, headache, lethargy, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XTANDI in patients who develop PRES.

Adverse Reactions
The most common adverse reactions (≥ 10%) that occurred more commonly (≥ 2% over placebo) in the XTANDI patients from the two placebo-controlled clinical trials were asthenia/fatigue, back pain, decreased appetite, constipation, arthralgia, diarrhea, hot flush, upper respiratory tract infection, peripheral edema, dyspnea, musculoskeletal pain, weight decreased, headache, hypertension, and dizziness/vertigo. In the bicalutamide-controlled study of chemotherapy-naïve patients, the most common adverse reactions (≥ 10%) reported in XTANDI patients were asthenia/fatigue, back pain, musculoskeletal pain, hot flush, hypertension, nausea, constipation, upper respiratory tract infection, diarrhea, and weight loss.

In the placebo-controlled study of patients taking XTANDI who previously received docetaxel, Grade 3 and higher adverse reactions were reported among 47% of XTANDI patients and 53% of placebo patients. Discontinuations due to adverse events were reported for 16% of XTANDI patients and 18% of placebo patients. In the placebo-controlled study of chemotherapy-naïve patients, Grade 3-4 adverse reactions were reported in 44% of XTANDI patients and 37% of placebo patients. Discontinuations due to adverse events were reported for 6% of both study groups. In the bicalutamide-controlled study of chemotherapy-naïve patients, Grade 3-4 adverse reactions were reported in 38.8% of XTANDI patients and 37.6% of bicalutamide patients. Discontinuations due to adverse events were reported for 7.6% of XTANDI patients and 6.3% of bicalutamide patients.

Lab Abnormalities: In the two placebo-controlled trials, Grade 1-4 neutropenia occurred in 15% of XTANDI patients (1% Grade 3-4) and 6% of placebo patients (0.5% Grade 3-4). Grade 1-4 thrombocytopenia occurred in 6% of XTANDI patients (0.3% Grade 3-4) and 5% of placebo patients (0.5% Grade 3-4). Grade 1-4 elevations in ALT occurred in 10% of XTANDI patients (0.2% Grade 3-4) and 16% of placebo patients (0.2% Grade 3-4). Grade 1-4 elevations in bilirubin occurred in 3% of XTANDI patients (0.1% Grade 3-4) and 2% of placebo patients (no Grade 3-4).

Infections: In the study of patients taking XTANDI who previously received docetaxel, 1% of XTANDI patients compared to 0.3% of placebo patients died from infections or sepsis. In the study of chemotherapy-naïve patients, 1 patient in each treatment group (0.1%) had an infection resulting in death.

Falls (including fall-related injuries) occurred in 9% of XTANDI patients and 4% of placebo patients in the two placebo-controlled trials. Falls were not associated with loss of consciousness or seizure. Fall-related injuries were more severe in XTANDI patients, and included non-pathologic fractures, joint injuries, and hematomas.

Hypertension occurred in 11% of XTANDI patients and 4% of placebo patients in the two placebo-controlled trials. No patients experienced hypertensive crisis. Medical history of hypertension was balanced between arms. Hypertension led to study discontinuation in < 1% of patients in each arm.

Drug Interactions
Effect of Other Drugs on XTANDI  Avoid strong CYP2C8 inhibitors, as they can increase the plasma exposure to XTANDI. If co-administration is necessary, reduce the dose of XTANDI.

Avoid strong CYP3A4 inducers as they can decrease the plasma exposure to XTANDI. If co-administration is necessary, increase the dose of XTANDI.

Effect of XTANDI on Other Drugs  Avoid CYP3A4, CYP2C9, and CYP2C19 substrates with a narrow therapeutic index, as XTANDI may decrease the plasma exposures of these drugs. If XTANDI is co-administered with warfarin (CYP2C9 substrate), conduct additional INR monitoring.

Please see Full Prescribing Information for additional safety information.

Reference: 1. Crawford ED, Stone NN, Yu EY, et al. Challenges and recommendations for early identification of metastatic disease in prostate cancer. Urology 2014;83(3):664-9.
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Indication and Important Safety Information

Indication

XTANDI (enzalutamide) capsules is indicated for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC).

Important Safety Information

Contraindications
XTANDI is not indicated for women. XTANDI can cause fetal harm and potential loss of pregnancy.