Efficacy and biomarker analysis of patients (pts) with advanced renal cell carcinoma (aRCC) with sarcomatoid histology (sRCC): Subgroup analysis from the phase III JAVELIN renal 101 trial of first-line avelumab plus axitinib (A + Ax) vs sunitinib (S)

Choueiri, Toni K.; Larkin, James; Pal, Sumanta K.; Motzer, Robert J.; Venugopal, Balaji; Alekseev, B. Ya.; Miyake, Hideaki; Gravis, G.; Bilen, Mehmet Asım; Chudnovsky, A.; Ching, Keith A.; Mariani, Mariangela; Robbins, Paul B.; Huang, Bo; Pietro, Alessandra di; Albigès, Laurence

doi:10.1093/annonc/mdz249.009

Cited by 33 publications

(29 citation statements)

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“…The avelumab plus axitinib arm achieved an improvement in ORR (46.8%, 95% CI 32.1-61.9; OR 3.249 95% CI 1.300-8.236) versus sunitinib (21.3%, 95% CI 11.9-33.7), and 2 patients receiving avelumab plus axitinib had a complete response compared with none receiving sunitinib. Additionally, treatment with combination agents resulted in a 3-month improvement in PFS (HR 0.57, 95% CI 0.325-1.003), as well as a 2.4-month improvement in duration of response for patients with sRCC when compared with sunitinib 180 . Overall, these results suggest that sRCCs may benefit from an immunotherapy plus VEGF-targeted therapy combination.…”

Section: High-dose Il-2mentioning

confidence: 99%

Sarcomatoid renal cell carcinoma: biology, natural history and management

et al. 2020

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Renal cancers are estimated to be diagnosed in 73,750 people in the USA in 2020, and to contribute to 14,830 deaths 1. The 2018 GLOBOCAN report on the global incidence of renal cancers has described 403,262 patients with renal cancer, and 175,098 deaths caused by renal cancers worldwide 2,3. Approximately 90% of all diagnosed renal parenchymal malignancies are renal cell carcinomas (RCCs) 4. A rare transformation called sarcomatoid dedifferentiation can occur in most RCC histological subtypes and portends an especially poor prognosis. RCCs in which sarcomatoid dedifferentiation has occurred are commonly referred to as sarcomatoid RCCs (sRCCs), and patients with sRCCs often present with advanced or metastatic disease and rarely survive >1 year 5-7. Sarcomatoid features are present in approximately 4-5% of all RCCs 8-11. However, this proportion can range from 1 to 29% depending on the primary histology and the reporting study 7,9-13. Although infrequently diagnosed in the localized setting (~20-40% of all sRCCs) 14,15 , approximately 20% of patients with metastatic RCC harbour sarcomatoid dedifferentiation 15. Patients commonly present with an sRCC at between 54 and 63 years of age 6,7,13,14,16,17 , and the male-to-female ratio ranges from 1.3:1 to 2:1 (refs 6,13,14,18,19). Similar to all other RCCs, the mechanisms underlying this gender difference remain unclear. However, possibilities include historical gender differences in occupational exposure or smoking habits, or the influence of sex hormones on tumour biology 20. The natural history and prognosis of sRCCs are poor, as approximately 60-80% of patients present with advanced or late-stage disease 14,15. Median survival is approximately 6-13 months and a higher percentage of sarcomatoid dedifferentiation on histology has been reported to confer a worse prognosis 6,7,11,21,22. Retrospective reports have shown reduced overall survival and cancer-specific survival in patients with increased sarcomatoid features 11,21. Compared with patients without sarcomatoid features, patients with ≥25% sarcomatoid features had ~30% increased overall risk of dying of any cause (HR 2.07, P = 0.048) 11 and those with ≥30% sarcomatoid features had a 52% increased risk of

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Section: High-dose Il-2mentioning

confidence: 99%

Sarcomatoid renal cell carcinoma: biology, natural history and management

et al. 2020

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“…Of the 177 full-texts of clinical studies involving the use of anti PD-1/PD-L1 agent in RCC that were evaluated, 6 full text articles [15][16][17][18][19][20] reporting data from RCTs were finally included in the quantitative meta-analysis. Furthermore, four abstracts [21][22][23][24] reporting sub-group analysis in sRCC were also included in the quantitative meta-analysis. The flow chart of the systematic review is reported in Figure 1.…”

Section: Eligible Articlesmentioning

confidence: 99%

Outcomes Associated with First-Line anti-PD-1/ PD-L1 agents vs. Sunitinib in Patients with Sarcomatoid Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

Buonerba

Dolce²,

Iaccarino

et al. 2020

Cancers

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: Immunotherapy based on anti PD-1/PD-L1 inhibitors has proven to be more effective than sunitinib in the first-line setting of advanced renal cell carcinoma (RCC). RCC patients with sarcomatoid histology (sRCC) have a poor prognosis and limited therapeutic options. We performed a systematic review and a meta-analysis of randomized-controlled trials (RCTs) of first-line anti PD-1/PDL-1 agents vs. sunitinib, presenting efficacy data in the sub-group of sRCC patients. The systematic research was conducted on Google Scholar, Cochrane Library, PubMed and Embase and updated until 31th January, 2020. Abstracts from ESMO and ASCO (2010–2019) were also reviewed. Full texts and abstracts reporting about RCTs testing first-line anti-PD-1/ PD-L1 agents vs. sunitinib in RCC were included if sRCC sub-group analyses of either PFS (progression-free survival), OS (overall survival) or radiological response rate were available. Pooled data from 3814 RCC patients in the ITT (intention-to-treat) population and from 512 sRCC patients were included in the quantitative synthesis. In the sRCC sub-group vs. the ITT population, pooled estimates of the PFS-HRs were 0.57 (95%: 0.45–0.74) vs. 0.79 (95% CI: 0.70–0.89), respectively, with a statistically meaningful interaction favoring the sRCC sub-group (pooled ratio of the PFS-HRs = 0.64; 95% CI: 0.50–0.82; p < 0.001). Pooled estimates of the difference in CR-R (complete response-rate) achieved with anti-PD-1/PDL-1 agents vs. sunitinib were + 0.10 (95% CI: 0.04–0.16) vs. + 0.04 (95% CI: 0.00–0.07) in the sRCC vs. the non-sRCC sub groups, with a statistically meaningful difference of + 0.06 (95% CI: 0.02–0.10; p = 0.007) favoring the sRCC sub-group. Sarcomatoid histology may be associated with improved efficacy of anti PD-1/PDL-1 agents vs. sunitinib in terms of PFS and CR-R.

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“…The results showed that PFS, OS, ORR and DCR were 5.9 m, 15.4 m, 26.7% and 60%, respectively 36 . In four phase 3 trials (Keynote‐426, CheckMate‐214, IMmotion151 and JAVELIN Renal 101), pembrolizumab, nivolumab, atezolizumab and avelumab were shown to bring survival benefit to SRCC in subgroup analyses 30, 37–40 . All these studies suggest that there are potential benefits of immunotherapy for SC, which might be helpful in the treatment of ESpCC.…”

Section: Discussionmentioning

confidence: 95%

Major pathological response after neoadjuvant immunotherapy in esophageal spindle cell carcinoma: A case report

Wang

et al. 2021

Thoracic Cancer

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Esophageal spindle cell carcinoma (ESpCC) is a rare subtype of esophageal carcinoma, accounting for 1% of all esophageal malignancies. The clinical outcome is unknown due to the lack of treatment options. Here, we present the case of a 60‐year‐old male with initially unresectable ESpCC, in which platinum‐based concurrent chemoradiotherapy was unsuccessful. He was subsequently treated with neoadjuvant immunotherapy and after surgery achieved a complete pathological response; therefore, neoadjuvant immunotherapy might be a novel option for ESpCC patients.

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Efficacy and biomarker analysis of patients (pts) with advanced renal cell carcinoma (aRCC) with sarcomatoid histology (sRCC): Subgroup analysis from the phase III JAVELIN renal 101 trial of first-line avelumab plus axitinib (A + Ax) vs sunitinib (S)

Cited by 33 publications

References 0 publications

Sarcomatoid renal cell carcinoma: biology, natural history and management

Sarcomatoid renal cell carcinoma: biology, natural history and management

Outcomes Associated with First-Line anti-PD-1/ PD-L1 agents vs. Sunitinib in Patients with Sarcomatoid Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

Major pathological response after neoadjuvant immunotherapy in esophageal spindle cell carcinoma: A case report

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