PDL-1 and PDL1 expressions in clear cell renal cell carcinoma (ccRCC) of metastatic patients with sunitinib first-line treatment.

Abstract Introduction: Nonclear cell (NCC) metastatic renal cell carcinoma (mRCC) is a biologically heterogeneous entity. We report the outcomes of NCC mRCC treated with first-line vascular endothelial growth factor (VEGF) inhibitors or mammalian target of rapamycin (mTOR) inhibitors at our institute. This is first such report from India. Methods: This is a retrospective analysis of the 40 consecutive patients of NCC mRCC treated between January 2013 and June 2015 in routine clinical practice at our institute. The primary endpoint analyzed was overall survival (OS) with respect to the type of first-line treatment and tumor histology. Results: The most common histological subtype was papillary in 25 patients (62.5%) followed by sarcomatoid in six (15%), chromophobe in 5 (12.5%), translocation-associated in one patient, and other nonspecified in three patients. First-line treatment was sorafenib in 14 (35%), sunitinib in 9 (22.5%), pazopanib in 8 (20%), everolimus in seven (17.5%), and best-supportive care (BSC) in two (5%) patients. Partial response, stable disease, and progression was observed in six (15%), 13 (32.5%), and nine (22.5%) cases, respectively, as the best response to first-line treatment. The median OS was 11.7 months and median event-free survival was 6.1 months in the whole cohort. The median OS in months for different first-line treatments were as follows: sorafenib (16.2), sunitinib (11.7), pazopanib (not reached, mean-23.9 ± 6.0), everolimus (4.1) and BSC (0.6) and for different histological subtypes were as follows: papillary (9.8), chromophobe (not reached, mean-30.3 ± 8.4), sarcomatoid (4.1), and others (7.9). Conclusions: Chromophobe histology has a better outcome compared to other histological subtypes, and anti-VEGF tyrosine kinase inhibitors are preferable first-line agents compared to mTOR inhibitors.

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Improving Outcomes in Metastatic Clear Cell Renal Cell Carcinoma by Sequencing Therapy

American Society of Clinical Oncology Educational Book ◽

10.14694/edbook_am.2014.34.e228 ◽

2014 ◽

pp. e228-e238 ◽

Cited By ~ 10

Author(s):

Manuela Schmidinger

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Drug Exposure ◽

Clear Cell ◽

Local Treatment ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Cell Renal Cell Carcinoma

Targeted agents have substantially improved outcomes in metastatic clear cell renal cell carcinoma. However, due to multiple mechanisms of evasive resistance, almost all patients progress at some point and may require subsequent therapies. Various agents have been explored after failure of first-line treatment in randomized clinical trials. However, so far few questions about the optimal sequence have been answered. Both everolimus and axitinib have been considered standard of care after failure of first-line VEGF-TKI; sorafenib has been proposed as an additional option. In clinical practice, several factors may influence the choice of subsequent treatment: these include considerations on appropriate drug exposure in first-line, gained insights on prognostic and predictive factors as well as mechanisms of resistance. Once the decision in second-line has been made and treatment has been initiated, treating physicians may already be challenged by the question of what to offer in third- and later lines. Treatment beyond second-line treatment isn't supported by strong evidence, and at this stage of disease, retrospective reports on rechallenge may help to guide decisions. In addition, local treatment approaches including metastasectomy and stereotactic radiosurgery may help to optimize outcomes in all treatment lines.

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Five-year survival analysis of interferon-a plus sorafenib versus sorafenib monotherapy as first-line treatment for metastatic clear cell renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.7_suppl.486 ◽

2015 ◽

Vol 33 (7_suppl) ◽

pp. 486-486

Author(s):

Ye Ding-Wei ◽

Zhang Hai-Lang

Keyword(s):

Renal Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Line Treatment ◽

First Line ◽

Cell Renal Cell Carcinoma ◽

Group A ◽

Group B ◽

First Line Treatment

486 Background: We compared the short- and long-term efficacy and safety of interferon-a plus sorafenib with sorafenib monotherapy as first-line treatment in metastatic clear cell renal cell carcinoma (mRCC) patients. Methods: mRCC patients who had not received systemic treatment were administered either interferon-a (300 MIU IM every other day) plus sorafenib (400 mg bid n=24, Group A) or sorafenib monotherapy (400 mg bid; n=24, Group B). Objective responses (OR; RECIST criterion ver 1.0) and differences in OR, progression-free survival (PFS), overall survival (OS) and toxicity were compared. Results: Sixty eight percent males were present in both the groups with comparable baseline demographic characteristics. After a median follow-up of 68 months, the OR was comparable (p=0.726) in Group A vs B; complete remission (1 vs 0 cases), partial remission (6 vs 7 cases), stable disease (14 vs 15 cases), and progressive disease (3 vs 3 cases). No significant difference was observed in the median PFS (p=0.965) and median OS (p=0.223) between both groups [9.4 months (95% CI: 5.8-17.4), Group A vs 14.0 months (95% CI: 9.9-18.0), Group B] and [32.9 months (95% CI: 8.2-87.1), Group A vs 20.4 months (95% CI: 16.2-24.6), Group B], respectively. The 5-year survival rate was higher in Group A vs B (46% vs 25%). Toxicity symptoms like fever (13 vs 3 cases), fatigue (15 vs 9 cases) and neutropenia (6 vs 1 cases) were more pronounced in Group A vs B. The incidence of hand and foot skin reactions, alopecia, rash, hypertension, liver dysfunction, hypophosphatemia, anemia, and other toxicities was similar in both groups. There were 14 (58.3%) and 8 (33.3%) cases of dosage reduction or suspension in Groups A and B, respectively. Conclusions: Short-term effect of interferon-a plus sorafenib as first-line treatment for mRCC was comparable to sorafenib monotherapy in terms of OR and PFS. Although higher toxicity was reported for interferon-a plus sorafenib, the combination holds promise for improving long-term OS.

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