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Concurrent olaparib increased severe dermatitis during radiotherapy for inflammatory breast cancer

Adding low-dose olaparib increased grade 3 dermatitis from 5.5% to 24.7% during postmastectomy radiotherapy for inflammatory breast cancer.

RadOncToday · ·1 min read

KEY POINTS

  • The phase II cooperative-group S1706 trial (NCT03598257) randomized patients with nonmetastatic T4d inflammatory breast cancer after neoadjuvant systemic therapy and modified radical mastectomy. This prespecified safety report included 146 evaluable participants, with 73 in each arm.
  • Both groups received 50 Gy to the chest wall and regional lymph nodes followed by a 10 Gy boost. Bolus was required to approximate full prescription dose at the skin; the experimental arm also received olaparib 25 mg twice daily throughout radiotherapy.
  • Grade 3 radiation dermatitis occurred in 24.7% of patients receiving olaparib versus 5.5% with radiotherapy alone (p = 0.003), representing an absolute increase of 19.2 percentage points.
  • Considering all acute treatment-related events in the chest-wall region, grade 3 toxicity occurred in 24.7% versus 6.8% (p = 0.006). One olaparib-treated patient developed early dense telangiectasia throughout the 50 Gy fields with radiation-induced lichenoid dermatitis.
  • Grade 2 or higher gastrointestinal toxicity occurred in 17.8% versus 0% (p < 0.001), while laboratory abnormalities of any grade occurred in 19.2% versus 0% (p < 0.001). Diarrhoea was more frequent with olaparib, and six patients developed grade 2 oesophagitis.
  • No grade 4 or 5 treatment-related events were reported. Extending observation to six months identified adverse events in 13.7% of patients in the olaparib arm, including three new grade 3 events: worsened dermatitis, pleural effusion, and restricted range of motion.
  • The primary efficacy outcome remains immature and was not reported. Treatment allocation was not blinded, but the randomized design, intensive weekly toxicity collection, and absence of delayed severe events in the control group strengthen the safety signal.

CLINICAL TAKEAWAY

Even olaparib at only 25 mg twice daily markedly intensified acute skin toxicity when combined with bolus-based chest-wall and nodal radiotherapy. Concurrent PARP inhibition should remain investigational; established adjuvant olaparib should continue to be sequenced rather than given simultaneously with breast radiotherapy.

SOURCE

International Journal of Radiation Oncology, Biology, Physics