medwireNews: The phase 1 RadioPARP trial points to the tolerability of administering olaparib concomitantly with adjuvant radiotherapy in patients with early-stage triple-negative breast cancer (TNBC) and residual disease after neoadjuvant chemotherapy.
Writing in JAMA Oncology, Pierre Loap and team from Institut Curie in Paris, France, explain that residual disease is an indicator of poor outcomes, and they hypothesize: “In this context, increasing the biological effectiveness of radiotherapy with radiosensitizers, such as PARP inhibitors, could theoretically achieve greater tumor control, resulting in improved clinical outcomes.”
They therefore evaluated the safety of olaparib in a dose-escalation trial comprising 24 women aged a median of 46 years who had an incomplete pathologic response after neoadjuvant chemotherapy (87.5%) or unresectable TNBC despite prior neoadjuvant chemotherapy (12.5%). Olaparib was administered at doses ranging from 50 mg twice daily to 200 mg twice daily, with treatment initiated a week before radiotherapy and continued concurrently.
No dose-limiting toxicities were observed over a median follow-up of 34 months and the maximum tolerated dose for olaparib was not reached. There were no deaths within 6 weeks of completion of olaparib plus radiotherapy.
Acute high-grade adverse events (AEs) included grade 3 or 4 lymphopenia in 45.8% of participants, grade 3 radiodermatitis in 8.3%, and grade 3 lymphocele and breast pain, each in 4.2%.
There was only one late AE of grade 3 or worse, namely grade 4 lymphopenia in one patient after 1 year of recruitment to the trial, and this was considered unrelated to the study regimen.
No patient experienced late grade 3 or more severe treatment-related AEs. One patient – who received olaparib 100 mg twice daily – reported grade 2 treatment-related breast pain, fibrosis, and deformity at both the 1- and 2-year follow-ups.
The other late treatment-related AEs were of grade 1, with the most common at 1 year being pain and skin hyperpigmentation, each in three patients, and at 2 years being telangiectasia, in four patients
Loap and colleagues also report preliminary efficacy outcomes, noting that the median event-free survival (EFS) and overall survival (OS) durations were not reached at the time of data cutoff. The EFS rates at 1, 2, and 3 years were 88%, 71%, and 65%, respectively, with corresponding OS rates of 96%, 83%, and 83%.
“These results suggest that use of olaparib as a radiosensitizer during breast radiotherapy may not be associated with an increased risk of late complications,” writes the team.
“Therefore, we recommend a radiosensitizing dose of 200 mg twice daily when combining olaparib with breast radiotherapy for future trials assessing the antitumor efficacy of this combination.”
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