Outcomes from second-line therapy in long-term responders to first-line tyrosine kinase inhibitor in clear-cell metastatic renal cell carcinoma

469 Background: SWITCH, a prospective, randomized sequential trial to evaluate SU/SO versus SO/SU, revealed no difference in first-line or total PFS or OS, but no direct comparison was obtained between 1st line sunitinib (SU) and sorafenib (SO) for clear cell (CC) metastatic renal cell carcinoma (mRCC). Methods: Treatment-naïve patients with CC mRCC, ECOG PS 0/1 and MSKCC favorable or intermediate risk were randomized to receive open-label SU/SO or SO/SU at the standard dosage and schedule. The primary endpoint was 1st line PFS, and secondary endpoints were total PFS and OS. The calculated sample size was 59 per group, with α = 0.05, β = 0.10, and a censoring rate of 15%. Results: Of 124 patients enrolled in this study from February 2010 to July 2012 from 39 institutions, 120 could be evaluated (SU/SO, 57 and SO/SU, 63). Baseline patients' characteristics in the SU/SO and SO/SU groups were as follows: favorable risk, 21% and 22%; and presence ofnephrectomy, 88% and 89%, respectively. First-line mPFS was 8.7 and 7.0 months in the SU/SO and SO/SU groups, respectively (HR, 0.67; 95% CI, 0.42–1.08; p= 0.095). There was no statistically significant difference in total (T)-PFS, 27.8 M, and 22.6 m (HR 0.73, CI 0.428-1.246; p=0.247), or OS 38.4 m and 30.9 m (HR 0.934, CI 0.588-1.485; p=0.773). Subgroup analyses showed that T-PFS was NR and 27.8 m (p=0.021) in the favorable risk, and 38.4 m and 16.1 m (p=0.009) in with less than 5 metastatic sites, 6.5 m and 13.6 m (p=0.025) without nephrectomy in the SU/SO and SO/SU groups, respectively. The most common adverse events (AEs) in case of first-line SU or SO (all grade, all cause) were hand–foot syndrome (71% vs. 86%), hypothyroidism (70% vs. 33%), fatigue (57% vs. 40%), hypertension (55% vs. 44%), and diarrhea (23% vs. 38%). AEs were generally lower during second-line therapy. Conclusions: There was no significant difference in first-line PFS, T-PFS, and OS between the two sequential treatments. Although fewer patients received second-line treatment in the SU/SO group, OS in this group was numerically longer than that in the SO/SU group. Clinical trial information: 01481870.

Download Full-text

Clinical and Pathological Characteristics of Metastatic Renal Cell Carcinoma Patients Needing a Second-Line Therapy: A Systematic Review

Cancers ◽

10.3390/cancers12123634 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3634

Author(s):

Nicola Longo ◽

Marco Capece ◽

Giuseppe Celentano ◽

Roberto La Rocca ◽

Gianluigi Califano ◽

...

Keyword(s):

Systematic Review ◽

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Group Performance ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Line Therapy

A high percentage of patients with metastatic renal cell carcinoma (mRCC) require a second-line option. We aimed to summarize available evidences about the clinicopathological profile of mRCC patients who receive a second-line therapy. A systematic review was performed in August 2020. We included papers that met the following criteria: original research; English language; human studies; enrolling mRCC patients entering a second-line therapy. Twenty-nine studies enrolling 7650 patients (73.5% male, mean age: 55 to 70 years) were included. Clear cell histology was reported in 74.4% to 100% of cases. Tyrosine kinase inhibitors, immunotherapy, bevacizumab, mTOR inhibitors, and chemotherapy were adopted as first line option in 68.5%, 29.2%, 2.9%, 0.6%, and 0.2% of patients, respectively. Discontinuation of first-line therapy was due to progression and toxicity in 18.4% to 100% and in 17% to 48.8% of patients, respectively. Eastern Cooperative Oncology Group performance status score was 0 or 1 in most cases. Most prevalent prognostic categories according to the International Metastatic RCC Database Consortium and Memorial Sloan–Kettering Cancer Centre score were intermediate and good. About 77.8% of patients harboured ≥2 metastatic sites. In conclusion, patients who enter a second-line therapy are heterogeneous in terms of a clinical-pathological profile. Tailoring of second-line treatment strategies is strongly advocated.

Download Full-text

Randomized Phase III Trial of Temsirolimus Versus Sorafenib As Second-Line Therapy After Sunitinib in Patients With Metastatic Renal Cell Carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2013.50.3961 ◽

2014 ◽

Vol 32 (8) ◽

pp. 760-767 ◽

Cited By ~ 248

Author(s):

Thomas E. Hutson ◽

Bernard Escudier ◽

Emilio Esteban ◽

Georg A. Bjarnason ◽

Ho Yeong Lim ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Phase Iii ◽

Second Line ◽

Second Line Therapy ◽

Phase Iii Trial ◽

Line Therapy

Purpose This international phase III trial (Investigating Torisel As Second-Line Therapy [INTORSECT]) compared the efficacy of temsirolimus (mammalian target of rapamycin inhibitor) and sorafenib (vascular endothelial growth factor receptor [VEGFR] tyrosine kinase inhibitor) as second-line therapy in patients with metastatic renal cell carcinoma (mRCC) after disease progression on sunitinib. Patients and Methods In total, 512 patients were randomly assigned 1:1 to receive intravenous temsirolimus 25 mg once weekly (n = 259) or oral sorafenib 400 mg twice per day (n = 253), with stratification according to duration of prior sunitinib therapy (≤ or > 180 days), prognostic risk, histology (clear cell or non–clear cell), and nephrectomy status. The primary end point was progression-free survival (PFS) by independent review committee assessment. Safety, objective response rate (ORR), and overall survival (OS) were secondary end points. Results Primary analysis revealed no significant difference between treatment arms for PFS (stratified hazard ratio [HR], 0.87; 95% CI, 0.71 to 1.07; two-sided P = .19) or ORR. Median PFS in the temsirolimus and sorafenib arms were 4.3 and 3.9 months, respectively. There was a significant OS difference in favor of sorafenib (stratified HR, 1.31; 95% CI, 1.05 to 1.63; two-sided P = .01). Median OS in the temsirolimus and sorafenib arms was 12.3 and 16.6 months, respectively. Safety profiles of both agents were consistent with previous studies. Conclusion In patients with mRCC and progression on sunitinib, second-line temsirolimus did not demonstrate a PFS advantage compared with sorafenib. The longer OS observed with sorafenib suggests sequenced VEGFR inhibition may benefit patients with mRCC.

Download Full-text

666P Pembrolizumab (pembro) monotherapy as first-line therapy in advanced clear cell renal cell carcinoma (ccRCC): Results after a minimum of 41 months of follow-up from KEYNOTE-427 cohort A

Annals of Oncology ◽

10.1016/j.annonc.2021.08.062 ◽

2021 ◽

Vol 32 ◽

pp. S691-S692

Author(s):

D.F. McDermott ◽

J-L. Lee ◽

G.A. Bjarnason ◽

J. Larkin ◽

R. Gafanov ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

First Line ◽

Cell Renal Cell Carcinoma ◽

First Line Therapy ◽

Line Therapy

Download Full-text

Evaluation of second line and subsequent targeted therapies in metastatic renal cell cancer (mRCC) patients treated with first line cediranib

Canadian Urological Association Journal ◽

10.5489/cuaj.2426 ◽

2014 ◽

Vol 8 (11-12) ◽

pp. 398 ◽

Cited By ~ 3

Author(s):

Suzanne Richter ◽

Jo-An Seah ◽

Gregory R Pond ◽

Hui K Gan ◽

Mary J. Mackenzie ◽

...

Keyword(s):

Renal Cell ◽

Kinase Inhibitor ◽

Cell Cancer ◽

Phase Iii ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Pivotal Phase ◽

Line Therapy ◽

To Receive

Introduction: Pivotal phase III trials have positioned angiogenesis inhibitors as first-line therapy for the management of most advanced or metastatic renal cell carcinomas (mRCC). Approaches to second-line therapy, however, remain more controversial with respect to drug selection and drug sequencing.Methods: In this study we evaluated mRCC patients who were initially treated on the first-line National Cancer Institute (NCI) trial with the highly potent vascular endothelial growth factor receptor tyrosine kinase inhibitor (TKI), cediranib, to determine the efficacy and tolerability of subsequent therapies.Results: Twenty-eight (65.1%) of the 43 patients enrolled on the first-line cediranib trial were known to receive second-line therapy, most commonly sunitinib (n = 21), with 4 (14%), 2 (7%) and 1 (3%) patients receiving temsirolimus, sorafenib, and interleukin, respectively. Of these, 14 (50%) went on to have 3 or more lines of therapy. The progression-free survival (PFS) proportion (PFS) at 1 year from starting second line was 30% (14.5%–47.9%). Longer duration of first-line cediranib treatment was modestly associated with longer duration of second-line treatment (Spearman rho 0.26). Patients who discontinued cediranib for toxicity were less likely to receive second-line sunitinib.Conclusion: In this real world evaluation, sequential use of TKIs for the management of mRCC was common. PFS with sequential TKIs was similar to observed and published results for any second-line therapy. Prior toxicity affected treatment patterns and the frequent use of at least 3 lines of therapy underscores the need for prospective sequencing trials in this disease.

Download Full-text