Highlights
- •Pictilisib is a potent class I pan-PI3K inhibitor.
- •The pictilisib combination treatments were feasible from a safety perspective.
- •No drug–drug interactions were observed in the combination treatment regimens.
- •Encouraging preliminary anti-tumour activity was observed.
Abstract
Aim
The phosphatidylinositol 3-kinase (PI3K) pathway is a potential therapeutic target
in non–small cell lung cancer (NSCLC). This study aimed to evaluate the pan-PI3K inhibitor
pictilisib in combination with first-line treatment regimens that were the standard
of care at the time of study, in patients with NSCLC.
Patients and methods
A 3 + 3 dose-escalation study was performed using a starting daily dose of 60 mg pictilisib
on days 1–14 of a 21-day cycle. Depending on bevacizumab eligibility and NSCLC histology,
patients also received either paclitaxel + carboplatin or pemetrexed + cisplatin,
± bevacizumab every 3 weeks. The primary objectives of the study were to assess safety
and tolerability and to identify dose-limiting toxicities (DLTs), the maximum tolerated
dose (MTD) and a recommended phase II dose (RP2D), for each combination.
Results
All 66 treated patients experienced at least one adverse event (AE). Grade ≥III AEs,
serious AEs and deaths occurred in 57 (86.4%), 56 (84.8%) and 9 (13.6%) patients,
respectively. Three patients reported DLTs across the four arms of the study. The
MTD was not reached in any arm and the RP2D of pictilisib was determined to be 330 mg
(capsules) or 340 mg (tablets) on a ‘14 days on, 7 days off’ schedule. The best confirmed
response was partial response in 29 (43.9%) patients and stable disease in 20 (30.9%)
patients.
Conclusion
Combining pictilisib with various standard-of-care first-line treatment regimens is
feasible from a safety perspective in patients with NSCLC, and encouraging preliminary
anti-tumour activity was observed.
Keywords
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Article info
Publication history
Published online: October 06, 2017
Accepted:
August 23,
2017
Received:
August 17,
2017
Identification
Copyright
© 2017 Elsevier Ltd. All rights reserved.
