How to manage fatigue induced by olaparib (Poly (ADP-ribose) polymerase inhibitor) in cancer patients?

Management of Olaparib-Induced Fatigue

Fatigue from olaparib should be managed primarily through patient education, energy conservation strategies, and a structured exercise program, with dose modifications reserved for grade 3 or higher fatigue that persists despite supportive measures. 1, 2

Understanding Olaparib-Related Fatigue

Olaparib causes fatigue in approximately 42-49% of patients, with most cases being grade 1-2 severity that peaks within the first 2 months of treatment. 2, 3 The risk of all-grade fatigue is 1.24 times higher compared to placebo, and high-grade fatigue is 1.71 times higher. 4 This fatigue is manageable without treatment discontinuation in most patients, allowing continued therapy as long as clinical benefit persists. 2

Initial Patient Education and Counseling

• Reassure patients that treatment-related fatigue does not indicate disease progression or treatment failure, as this fear is a primary reason for underreporting symptoms. 5
• Educate patients before starting olaparib that fatigue may occur as a consequence of therapy and typically peaks early in treatment. 5, 2
• Instruct patients to maintain a daily fatigue diary using a 0-10 numeric rating scale (0 = no fatigue; 10 = worst fatigue), with scores of 1-3 indicating mild, 4-6 moderate, and 7-10 severe fatigue. 5

Energy Conservation Strategies (First-Line Approach)

• Teach patients to schedule activities during peak energy periods by maintaining a daily and weekly diary to identify when energy levels are highest. 5
• Prioritize essential activities and delegate or postpone nonessential tasks when experiencing moderate to severe fatigue. 5
• Implement labor-saving techniques such as using reachers for grasping items, rolling carts for transporting objects, and wearing a bathrobe instead of toweling off after bathing. 5
• Limit daytime naps to less than 1 hour to avoid disrupting nighttime sleep quality. 5
• Use distraction techniques including games, music, reading, and socializing to help decrease fatigue perception. 5

Physical Activity (Category 1 Recommendation)

Exercise is the most strongly evidence-based intervention for cancer-related fatigue and should be initiated as tolerated. 5

• Recommend a combination of moderate-intensity endurance exercises (walking, jogging, swimming) and resistance training with light weights. 5
• Exercise should be prescribed cautiously in patients with bone metastases, thrombocytopenia, anemia, fever, or active infection. 5
• Consider referral to physical therapy or occupational therapy for patients who are significantly deconditioned or have treatment-related limitations. 5

Psychosocial Interventions (Category 1 Recommendation)

• Cognitive behavioral therapy (CBT) has strong evidence for reducing fatigue and should be offered to patients with persistent moderate-to-severe symptoms. 5
• Mindfulness-based stress reduction, psychoeducational therapies, and supportive-expressive therapies are all evidence-based options. 5
• CBT for sleep disturbances (Category 1 recommendation) should be implemented, as optimizing sleep quality directly improves fatigue levels. 5

Nutritional and Sleep Optimization

• Refer patients to nutritional consultation to address any dietary deficiencies or alterations that may contribute to fatigue. 5
• Establish consistent sleep and wake times, eliminate electronic devices before bedtime, and avoid caffeine and alcohol in the evening. 5
• Screen for and aggressively treat sleep disorders, as these are common contributors to both fatigue and may be independent of olaparib therapy. 5

Evaluation of Treatable Contributing Factors

Before attributing fatigue solely to olaparib, assess and treat the following:

• Anemia: Olaparib causes anemia in 50% of patients (17% grade 3+), which is 2.10 times more common than placebo for all-grade anemia and 3.15 times more common for high-grade anemia. 4, 2, 3 Manage anemia according to standard guidelines, as this is a major treatable contributor to fatigue.
• Pain, emotional distress, and other concurrent symptoms that frequently cluster with fatigue. 5
• Thyroid dysfunction, nutritional deficiencies, and other metabolic causes. 5

Olaparib Dose Modifications

Most olaparib-related fatigue is manageable with supportive care alone; dose modifications should be reserved for persistent grade 3+ fatigue. 2

• Fatigue and other common adverse events in olaparib trials were primarily managed through dose interruptions or dose reductions rather than discontinuation. 2
• The majority of fatigue events were grade 1-2 and peaked within the first 2 months, then improved with management strategies. 2, 3
• Continue olaparib at full dose if possible while implementing supportive measures, as maintaining dose intensity correlates with continued clinical benefit. 1, 2

Pharmacologic Interventions (Limited Role)

• Methylphenidate may be considered after ruling out other treatable causes of fatigue, but should be used cautiously and only after treatment- and disease-specific morbidities have been characterized. 5
• Optimal dosing and schedule for psychostimulants in cancer patients have not been established. 5
• Treat underlying conditions such as hypothyroidism with levothyroxine if identified. 5

Monitoring and Reassessment

• Screen for fatigue at every clinical visit using standardized assessment tools. 5
• Reassess fatigue levels regularly after implementing interventions to document improvement and adjust management strategies. 5
• If fatigue remains unresolved despite treating contributing factors and implementing nonpharmacologic interventions, consider referral to supportive care specialists experienced in fatigue management. 5

Key Clinical Pitfalls to Avoid

• Do not automatically reduce olaparib dose at the first report of fatigue; most cases are grade 1-2 and manageable with supportive care. 2, 3
• Do not overlook anemia as a major treatable contributor—olaparib significantly increases anemia risk, and addressing this can substantially improve fatigue. 4, 2
• Do not dismiss patient reports of fatigue as "expected" without implementing evidence-based management strategies, as this significantly impacts quality of life. 1
• Do not prescribe psychostimulants before thoroughly evaluating and treating reversible causes of fatigue. 5