ASCO 2014 - Abstract 4520 & 4521

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. 

The results from these 2 abstracts are not practice changing, as ‘watch and wait’ and treatment holidays were already in use, but they give some guidance as to whom it should be offered.

Considering withholding therapy for patient with metastatic disease, the results do seem to indicate that patients can enjoy a long period without therapy inducing side effects. However, the results presented by Rini et al provide insight into the fact that patients selected by the tumor bulk at diagnosis of metastatic disease is indicative. In fact, the ‘watch and wait’ attitude was particularly relevant for patients with a tumor bulk of less than 3.0cms. These data could therefore guide physicians at identifying patients for whom ‘watch and wait’ is an adequate clinical option and to partly predict the period of time that patients can expect to enjoy without initiating therapy.

The data on drug holidays was obtained from retrospective data and is therefore exploratory in nature. There is therefore a bias in patient selection. Patients had previously stopped therapy because of adverse events or reasons other than tumor progression. These patients basically represent a population of good responders for whom continuation of therapy was not deemed necessary when the treatment was terminated. The period without therapy was rather long, especially after cessation of first line therapy. Data on patients offered a drug holiday in second and further lines of therapy was rather minimal and is representative of the fact that this clinical option of drug holiday is a rather rare occurrence after first line therapy, as second and third line agents are linked with rather low response rates of 5 to 10%. This study is therefore informing us on the fact that for patients with a good response to first line therapy could be offered a drug holiday, especially if the patient is experiencing significant adverse events, and that reinitiation of therapy at disease progression or when treatment becomes necessary is associated with adequate response rates.
— CARE Genitourinary Cancer Faculty