Guidelines for Management of Treatment-Emergent Adverse Events During Rucaparib Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer

Figures & data

Table 1 Most Frequently Occurring (≥20%) TEAEs of Any Grade with Rucaparib in Men with mCRPC and a BRCA Alteration

	BRCA Cohort (n=115)
	Any Grade, %	Grade ≥3, %
Asthenia/fatigue	62	9
Nausea	52	3
Anemia^a	43	25
Increased ALT/AST	33	5
Decreased appetite	28	2
Rash^b	27	2
Constipation	27	1
Thrombocytopenia^c	25	10
Vomiting	22	1
Diarrhea	20	0

Notes: Visit cutoff date: September 13, 2019. TEAEs were graded according to NCI CTCAE version 4.03. There were no TEAEs of myelodysplastic syndrome or acute myeloid leukemia reported. ^aIncludes anemia and decreased hemoglobin. ^bIncludes blister, blood blister, dermatitis, dermatitis contact, eczema, genital rash, palmar-plantar erythrodysesthesia syndrome, photosensitivity reaction, psoriasis, rash, rash maculo-papular, rash pruritic, skin exfoliation, skin lesion, and urticaria. ^cIncludes thrombocytopenia and platelet count decreased. Adapted from Clovis Oncology. Rubraca (Rucaparib) Tablets [Prescribing Information]. Available from: https://clovisoncology.com/pdfs/RubracaUSPI.pdf.¹⁰

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; mCRPC, metastatic castration-resistant prostate cancer; NCI CTCAE, National Cancer Institute-Common Terminology Criteria for Adverse Events; TEAE, treatment-emergent adverse event.

Figure 1 Median time to first onset for the most frequently occurring (≥20%) TEAEs of any grade with rucaparib in men with mCRPC and a BRCA alteration. *Includes blister, blood blister, dermatitis, dermatitis contact, eczema, genital rash, palmar-plantar erythrodysesthesia syndrome, photosensitivity reaction, psoriasis, rash, rash maculo-papular, rash pruritic, skin exfoliation, skin lesion, and urticaria. ^†Includes anemia and decreased hemoglobin. ^‡Includes thrombocytopenia and platelet count decreased.

Abbreviations: mCRPC, metastatic castration-resistant prostate cancer; NA, not applicable; TEAE, treatment-emergent adverse event.

Table 2 Guidelines for TEAEs Frequently Observed in Patients with mCRPC

TEAE	Management Recommendations
Asthenia/fatigue^Citation41	Grades 1–2 ● Implement lifestyle adjustments for energy conservation and self-monitoring (eg, structured daily routine, exercise program tailored to limiting factors such as bone metastases or fall risk) ● Consider nonnpharmacologic (eg, CBT) interventions		Grades 3–4 ● Evaluate for other contributing factors (eg, pain, anemia, nausea, vomiting, endocrinopathies, concomitant medications, emotional distress^Citation44) and manage accordingly ● Assess for underlying mood disorders (eg, major depressive disorder) and provide pharmacologic (eg, SSRI, SNRI) or nonpharmacologic intervention as needed
Nausea/vomiting^Citation45,Citation46	All grades ● Implement lifestyle adjustments (eg, eat small frequent meals, eat food at room temperature, take rucaparib later in the day^Citation47) ● Consider antiemetic medications (eg, 5-HT3 receptor antagonists, neurokinin-1 antagonists, dopamine antagonists, corticosteroids) if symptoms are not controlled with conservative measures  o Addition of or switch to another agent may be required for adequate control ● Dose adjustments and/or interruption may be necessary to achieve adequate control of symptoms in more severe cases
Decreased appetite^a	All grades ● Encourage patients to eat their favorite foods and have small and frequent meals
Constipation^Citation48	All grades ● Evaluate to exclude other causes (eg, pain medication, antiemetics) ● Implement lifestyle adjustments (eg, increased fluid intake, maintaining activity/mobility) ● Use osmotic or stimulant laxatives when needed ● Provide suppositories and/or enemas for patients with full rectum or fecal impaction
Diarrhea^Citation49	All grades ● Evaluate to exclude other causes	Grades 1–2 ● Maintain oral hydration ● Modify diet (eg, avoid lactose) ● Consider providing antidiarrheal medication^b		Grades 3–4^c ● Provide antidiarrheal medication, intravenous fluids, and electrolyte replacement ● Evaluate for infection and provide antibiotics if confirmed

Notes: ^aAuthor recommendation. ^bIf diarrhea is not sufficiently controlled by the selected antidiarrheal medication, consider adding or replacing it with a second medication that has a different mechanism of action. ^cOr for patients with related complications (eg, severe cramping, dehydration).

Abbreviations: 5-HT₃, 5-hydroxytryptamine type 3 (serotonin); CBT, cognitive behavioral therapy; SNRI, serotonin-norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TEAE, treatment-emergent adverse event.

Figure 2 Mean ALT (A, blue), AST (A, red), and creatinine (B, purple) values for patients in the BRCA cohort of TRITON2. Horizontal lines represent the upper and lower limits of normal for each laboratory parameter. Error bars represent standard error of the mean.

Abbreviations: ALT, alanine aminotransferase. AST, aspartate aminotransferase. SE, standard error. Reproduced with permission from Abida W, Patnaik A, Campbell D, et al. Rucaparib in men with metastatic castration-resistant prostate cancer harboring a BRCA1 or BRCA2 gene alteration. J Clin Oncol. 2020;38(32):3763–3772; Supplementary Figures S12 and S13, https://ascopubs.org/doi/10.1200/JCO.20.01035 © Abida et al.¹²

Figure 3 Guidelines for managing transaminitis. *Decline to grade 2 or lower. ^†If bilirubin and alkaline phosphatase levels remain elevated, we recommend evaluating for alternate etiologies of liver injury, such as hepatic metastases or viral hepatitis; consultation with a hepatologist may be considered.

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ULN, upper limit of normal.

Figure 4 Guidelines for managing rash/photosensitivity. *If refractory and/or severe (eg, grade 3 or 4), early referral to a dermatologist is recommended.

Abbreviation: SPF, sun protection factor.

Figure 5 Mean hemoglobin (A) and platelet (B) values for patients in the BRCA cohort of TRITON2. Horizontal lines represent the upper and lower limits of normal for each laboratory parameter. Error bars represent standard error of the mean. (Data on file. Clovis Oncology, Inc. 2021).

Figure 6 Guidelines for managing hematologic TEAEs.*If applicable per local guidelines.

Abbreviation: TEAE, treatment-emergent adverse event.

Figure 7 Guidelines for managing serum creatinine elevations. *Dose adjustments are not necessary for patients with a mild-to-moderate reduction in glomerular filtration rate (creatinine clearance of 30–89 mL/min).¹⁰

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