462P - A phase IB clinical study with 18F-FDG-PET response evaluation of the combination of temsirolimus (T) and pegylated liposomal doxorubicin (PLD) in b...

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Anticancer agents
Breast Cancer
Gynaecological Malignancies
Therapy
Biological Therapy
Presenter Marye Sonderen
Authors M.J. Sonderen1, I.M.E. Desar2, L. De Geus-Oei3, W.T.A. van der Graaf2, W.J.G. Oyen4, P.B. Ottevanger5, C. van Herpen2
  • 1Radboud University Medical Centre Nijmegen, 6500 HB - Nijmegen/NL
  • 2Department Of Medical Oncology/452, Radboud University Medical Centre Nijmegen, 6500 HB - Nijmegen/NL
  • 3Department Of Nuclear Medicine, Radboud University Nijmegen Medical Centre, 6500HB - Nijmegen/NL
  • 4Department Of Nuclear Medicine, Radboud University Nijmegen Medical Centre, 6500 HB - Nijmegen/NL
  • 5Medical Oncology, Radboud University Medical Centre Nijmegen, 6500 HB - Nijmegen/NL

Abstract

Background

PLD is active in metastatic breast, endometrial and ovarian cancer. Preclinical data suggest that mTOR inhibitors can reverse resistance to doxorubicin. Therefore, the combination of T and PLD is promising.

Methods

This phase I study assessed the MTD, safety and activity of the combination of T and PLD in advanced or recurrent breast, endometrial or ovarian cancer. After a 2 wk run in period with T iv once weekly, PLD iv once every 4 wks was added. The MTD was defined as the highest dose at which ≤ 1 DLT had been observed among 6 pts. FDG PET scans were performed at baseline (B), after 2 and 6 wks to assess the effect on tumor metabolism. A CT scan was performed for RECIST evaluation at B and after 10 wks. PET scans were evaluated by SUV analysis and total lesion glycolysis (TLG). The fractional change in SUV and TLG between the first, second and third FDG-PET was calculated.

Results

20 pts were enrolled. On the 4th dose level with 20 mg T and 40 mg/m2 PLD 2 DLTs occurred in 6 pts, a grade 3 thrombocytopenic bleeding and a grade 3 skin toxicity. Thus the MTD was assessed at 15 mg T and 40 mg/m2 PLD. AEs occurring most frequently were (all grds/grd 3-4 (%)) fatigue (84/5), nausea (84/16) and mucositis (79/21). 3 pts showed PR and 9 SD (> 3 months). The mean PFS was 4.9 months with 2 pts still on treatment. The fractional decrease in TLG from the first to the second FDG-PET for PR pts differed from those who had not (p= 0.018 for ΔTLG50). The fractional change in SUVmax from the second to the third FDG-PET differed between pts who had PD and those who had not (+14.0 versus -15.8, p = 0.034). The degree of decrease in SUVmax between the FDG-PET made after 2 and 6 wks was associated with better PFS (HR 1.068; p = 0.013).

Conclusions

The combination of T and PLD is safe and tolerable. The MTD was assessed at PLD 40 mg/m2 once every 4 wks and T 15 mg weekly. Early response evaluation with FDG-PET could predict PR and PD early after start of treatment. The activity of this combination in breast, endometrial and ovarian cancer pts is promising and warrants further studies with FDG-PET evaluation.

Disclosure

All authors have declared no conflicts of interest.