ASCO 2014. Abstract 4520. A prospective observational study of metastatic renal cell carcinoma (mRCC) prior to initiation of systemic therapy
Brian I. Rini, Tanya B. Dorff, Paul Elson, Cristina Suarez, Jordi Humbert, Linda Pyle, James M. G. Larkin, Elizabeth R. Plimack; Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH; USC Norris Comprehensive Cancer Center, Los Angeles, CA; Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH; Vall d'Hebron University Hospital, Barcelona, Spain; Vall d’Hebron, Barcelona, Spain; The Royal Marsden NHS Foundation Trust, London, United Kingdom; Royal Marsden Hospital, London, United Kingdom; Fox Chase Cancer Center, Philadelphia, PA
Background: The biology of mRCC includes a subpopulation of patients (pts) with indolent growth. Because of the toxicity and non-curative nature of current systemic therapy, select pts may be better served with initial surveillance. A prospective phase II observation trial was conducted in pts with mRCC prior to initial systemic treatment.
Methods: Pts with treatment-naïve, asymptomatic, histologically-confirmed mRCC and metastases were enrolled. Local therapy prior to and during the study was permitted. Radiographic assessment was performed at baseline, every 3 months for year 1, every 4 months for year 2, then every 6 months. The primary objective was to characterize time to initiation of systemic treatment. Secondary endpoints included assessment of depression/anxiety using standardized questionnaires (FKSI-DRS and HADS) and peripheral blood immune repertoire (TH1/TH2, MDSC, Tregs). Target accrual of 50 pts provided adequate power for the primary descriptive endpoint and 80% power to detect changes in correlate endpoints based on a two-sided Wilcoxon signed rank test.
Results: 52 pts were accrued; median age 67 (range, 47-88); 75% male; 94% ECOG 0; 96% clear cell; 8% prior metastasectomy and Heng risk group favorable/intermediate 26%/74%. Baseline tumor burden (per RECIST 1.0) was 3.2cm (0.8-19.6cm). Median time on observation until systemic therapy was started was 14.1 months (95% C.I. 10.6-19.3), with estimated 12 month and 24 month rates of continued surveillance of 58% and 33%, respectively. Median change in tumor burden on study was 0.8cm (0-6.5cm); relative change +34% (0-311%) and median growth rate 0.14 cm/month (0-1.75). 31 pts have come off observation (61% for PD), and 25 pts have received systemic therapy. Pts with baseline tumor burden ≤1.5 cm vs. >1.5 cm had a median observation period of 31.6 months vs. 13.8 months (p=0.06). Neither location nor number of metastatic sites impacted the length of observation. Anxiety/depression were not prevalent at baseline, and scores did not worsen over time. There were no significant changes in immunologic parameters.
Conclusions: A subset of mRCC pts can be safely observed for a period of time before starting systemic therapy.
ASCO 2014. Abstract 4521. Outcomes of treatment cessation in select metastatic renal cell carcinoma (mRCC) patients.
Kriti Mittal, Lisa Derosa, Laurence Albiges, Laura S. Wood, Paul Elson, Timothy D. Gilligan, Jorge A. Garcia, Robert Dreicer, Bernard J. Escudier, Brian I. Rini; Cleveland Clinic, Cleveland, OH; Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France; Institut Gustave Roussy, Villejuif, France; Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH; Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH
Background: Tyrosine kinase inhibitors (TKIs) demonstrate efficacy in mRCC, but may cause significant adverse effects (AEs). We have previously evaluated outcomes in patients (pts) receiving prolonged treatment breaks on TKIs and expand and update this experience herein.
Results: Baseline characteristics (n=112) were: 75% male; median age at diagnosis 56; 95% clear cell. 19% pts had received prior systemic therapy. 48% pts were favorable, 48% intermediate and 4% poor risk by Heng criteria. Table 1 depicts outcomes with sequential lines of therapy. Overall, pts received a median of 2 treatments. Treatment A primarily included sunitinib (55%), sorafenib (13%), or bevacizumab in combination with temsirolimus (10%)/ interferon (9%). Common reasons for breaks in treatment A were toxicity/AEs (57%) & physician choice (26%). 40 (36%) pts remain on treatment break from the first treatment (A). 25 (22%) pts have undergone 2 treatment breaks. 68 (61%) pts restarted treatment (B); 33 (49%) of these were rechallenged with previously used therapy & 35 (51%) received alternative TKIs. Overall, 30 patients have died; median survival is 71.7 months (range 1.3- 93+ months). Achievement of CR prior to the initial treatment break (n=15) was associated with a longer surveillance period (p=.0004).
Conclusions: A treatment break is feasible in selected pts, especially after achievement of CR with TKIs. This strategy may be associated with acceptable overall disease control and reduced toxicity.