Olaparib combined with radiotherapy for TNBC: 1-year toxicity report of the RADIOPARP phase 1 trial
OC-0630
Abstract
Olaparib combined with radiotherapy for TNBC: 1-year toxicity report of the RADIOPARP phase 1 trial
Authors: Pierre Loap1, Delphine Loirat2, Frédérique Berger3, Manuel Rodrigues2, Louis Bazire1, Jean-Yves Pierga2, Francesco Ricci4, Kim Cao1, Anne Vincent-Salomon5, Fatima Laki6, Cyrine Ezzili3, Anne Jochem3, Laurence Raizonville3, Veronique Mosseri3, Monia Ezzalfani3, Alain Fourquet1, Youlia Kirova1
1Institut Curie, Department of Radiation Oncology, Paris, France; 2Institut Curie, Department of Medical Oncology, Paris, France; 3Institut Curie, Department of Statistics, Paris, France; 4Institut Curie, Clinical Investigation Unit, Paris, France; 5Institut Curie, Department of Pathology, Paris, France; 6Institut Curie, Department of Surgery, Paris, France
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Purpose or Objective
Triple-negative
breast cancer (TNBC) cells are sensitive to PARP1 inhibitors in vitro. The combination
of Olaparib and radiotherapy for TNBC is currently evaluated in the phase I
RADIOPARP trial. During the dose-escalation portion of this study, Olaparib was
escalated to 200 mg twice a day, corresponding to the target dose, without dose-limiting
toxicities. The one-year toxicity profile of this combination is reported.
Material and Methods
RADIOPARP is a monocentric prospective open-label phase I dose-escalation
trial evaluating the combination of breast radiotherapy and Olaparib in TNBC patients
with inflammatory, locoregionally advanced or metastatic
disease, or with residual disease after neoadjuvant chemotherapy. Olaparib
was orally given at increasing dose levels (50mg, 100mg, 150mg or 200mg twice a
day); radiotherapy consisted of 50 Gy to the breast or chest wall with or
without lymph node irradiation. Treatment-related toxicity was graded according
to the CTCAE (version 4.03).
Results
Twenty-four
TNBC patients were enrolled between 09/2017 and 11/2019. Olaparib was escalated
to 200 mg twice a day without dose-limiting toxicities. At one-year follow-up,
no treatment-related grade ≥3 toxicity was observed (Table 1). Three
patients had persistent grade 2 adverse events (breast pain, fibrosis and deformity).
There were no cardiac, pulmonary or digestive toxicity.
|
Adverse events/Grade
|
1
|
2
|
3
|
4
|
|
Pain
|
3
|
1
|
0
|
0
|
|
Fibrosis
|
0
|
1
|
0
|
0
|
|
Deformity
|
0
|
1
|
0
|
0
|
|
Skin hyperpigmentation
|
3
|
0
|
0
|
0
|
|
Telangiectasia
|
1
|
0
|
0
|
0
|
|
Lymphedema
|
1
|
0
|
0
|
0
|
|
|
|
|
|
|
Table 1 : One-year treatment-related adverse events (CTCAE version 4.03)
Conclusion
the one-year follow-up report
of the RADIOPARP phase I trial, evaluating Olaparib associated with breast
radiotherapy in TNBC patients, demonstrated an acceptable toxicity profile of
this combination with few low-grade adverse events.