Randomized Phase Ii Study of First-Line Everolimus (Eve) + bevacizumab (Bev) Versus Interferon Alfa-2a (Ifn) + bev in Patients (Pts) With Metastatic Renal Cell Carcinoma (Mrcc): Record-2

Ravaud, Alain; Barrios, Carlos H.; Anak, Oezlem; Pelov, Diana; Louveau, Anne-Laure; Алексеев, Б. Я.; Mh, Tattersall; Agarwala, Sanjiv S.; Yalçin, Sıddıka Songül; Melichar, Bohuslav; McDermott, David F.; Drake, Charles G.; Sznol, Mario; Choueiri, Toni K.; Powderly, J.D.; Smith, David C.; Wigginton, Jon M.; Kollia, Georgia; Gupta, Ankush; Atkins, Michael B.; Donskov, Frede; Michaelson, M. Dror; Puzanov, Igor; Davis, Matthew; Bjarnason, Georg A.; Motzer, Robert J.; Lin, Xun; Cohen, D.P.; Wiltshire, Robin; Rini, Brian I.; Oudard, S.; Culine, Stéphane; Vieillefond, Annick; Priou, Frank; Goldwasser, François; Gravis-Mescam, G.; Deplanque, Gaël; Machiels, J.-P.; Beuzeboc, Philippe; Sonpavde, Guru; Maughan, Benjamin L.; Boucher, Kenneth M.; Fougeray, Ronan; Niegisch, Günter; Wong, Yu‐Ning; Sridhar, Srinivas; Sternberg, Cora N.; Bellmunt, Joaquim; Booth, Chris; Siemens, D. 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doi:10.1093/annonc/mds399

Cited by 25 publications

(2 citation statements)

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“…Результаты исследований комбинации бевацизумаба и эверолимуса оказались разнонаправленными: в исследовании SCRI продемонстрирована хорошая переносимость комбинации в 1 и 2-й линиях терапии, при этом отмечена необходимость в дополнительных исследова-ниях [42]. Однако во 2-м исследовании RECORD-2 первичная конечная точка (ВБП) не достигнута [43]. В связи с этим данная комбинация не зарегистрирована.…”

Section: комбинированная лекарственная терапия мпкрunclassified

Combination therapy regimens in the treatment of metastatic renal cell carcinoma: A review

2022

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Renal cell carcinoma (RCC) is one of the most common tumor types in urologic oncology practice. Despite the improvement of diagnostics methods, about 1/3 of patients with renal cell carcinoma have distant metastases at presentation resulting in an extremely high death rate. For many years, treatment of advanced forms of RCC was utterly ineffective. Standard chemotherapy regimens with fluoropyrimidines and antitumor antibiotics, cytokine therapy with interleukin-2, and interferon- only slightly prolonged the life of patients while causing severe toxic side effects and anemia. Attempts to treat the tumor with radiation therapy have also failed and have been used only for symptomatic treatment of distant metastases. The introduction of tyrosine kinase inhibitors (TKIs) in the treatment of metastatic RCC (mRCC) has enabled much more significant results. Thus, a landmark event was the approval of TKIs sunitinib and then sorafenib, pazopanib, axitinib, lenvatinib, cabozantinib, and mammalian target of rapamycin (mTOR) inhibitors: everolimus and temsirolimus. Subsequent combined therapy using bevacizumab with low-dose interferon- and lenvatinib with everolimus improved recurrence-free survival and objective response rates but contributed to increased toxicity of therapy. The next step in RCC therapy was the approval of the combination of the immuno-oncology agents ipilimumab and nivolumab for the treatment of mRCC by the U.S. Food and Drug Administration in April 2018. Later, combinations of immune checkpoint inhibitors with targeted agents were approved, which increased the life expectancy of patients and reduced the toxicity of antitumor therapy. One of the most effective regimens is the combination of a TKI axitinib or lenvatinib with the PD-1 inhibitor pembrolizumab. This article addresses the current progress in the treatment of patients with mRCC, reviewing the results of completed clinical trials on the use of combination therapy with targeted and immuno-oncology agents.

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Section: комбинированная лекарственная терапия мпкрunclassified

Combination therapy regimens in the treatment of metastatic renal cell carcinoma: A review

2022

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“…The randomized, phase 3 INTORACT trial (bevacizumab plus temsirolimus vs bevacizumab plus interferon‐α [IFN‐α] in advanced RCC) failed to demonstrate an advantage with bevacizumab/temsirolimus compared with bevacizumab/IFN‐α . Similarly, no benefit was observed with the combination of bevacizumab/everolimus (vs bevacizumab/IFN‐α) in the phase 2 RECORD‐2 study . There is little rationale to suggest that the combination of ramucirumab with either available mTOR inhibitor would yield superior results.…”

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Ramucirumab in metastatic renal cell carcinoma: The beginning or the end?

Pal

Figlin

2014

Cancer

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In this issue of Cancer, Garcia et al report results from a phase 2 trial of ramucirumab in patients with metastatic renal cell carcinoma (mRCC).1 Ramucirumab, an immunoglobulin G1 (IgG1) monoclonal antibody with affinity for the extracellular domain of vascular endothelial growth factor receptor-2 (VEGFR2), was recently granted priority review by the US Food and Drug Administration on the basis of the phase 3 REGARD trial (ramucirumab monotherapy for previously treated advanced gastric or gastroesophageal junction adenocarcinoma). 2 In that study, patients with advanced gastric cancer who had failed prior platinum-based or fluoropyrimidine-based therapy and received ramucirumab with best supportive care (BSC) had a prolongation in both progression-free survival (PFS) and overall survival (OS) compared with patients who received ramucirumab alone. Even more recently, the phase 3 RAINBOW trial (ramucirumab plus paclitaxel vs placebo plus paclitaxel in the treatment of metastatic gastroesophageal junction and gastric adenocarcinoma after disease progression on first-line platinum-containing and fluoropyrimidine-containing combination therapy) suggested a benefit of OS with the combination of paclitaxel and ramucirumab (vs paclitaxel with placebo) in a similar setting.3 These data come on the heels of results from a separate, negative phase 3 trial of ramucirumab in metastatic breast cancer. 4 With the mixed pool of results amassed thus far, what will be the ultimate fate of ramucirumab in mRCC?The results reported by Garcia et al provide several key insights but may be insufficient to fully address this question. The trial evaluated 40 patients with mRCC who had received prior therapy with sorafenib and/or sunitinib. The study failed to meet its primary endpoint, reporting an objective response rate (ORR) of just 5.1%. The selection of ORR as a primary endpoint in phase 2 trials has been the subject of much debate, especially given that all phase 3 trials in mRCC to date that have led to drug approvals have used PFS. The PFS data from this phase 2 experience (7.1 months) is perhaps more encouraging than the observed ORR. Acknowledging the caveats of any cross-trial comparison, these data compare favorably to the PFS associated with everolimus in a phase 3 trial of daily oral everolimus for RCC (the RECORD-1 trial) (4.0 months) and with axitinib in a phase 3 trial of axitinib versus sorafenib in advanced RCC (the AXIS trial) (6.7 months). 5,6 Although the eligibility criteria of the current study closely mirror those in RECORD-1, it is worth noting that AXIS only permitted 1 prior line of therapy (either cytokine or targeted therapy)-in the subset of patients receiving axitinib after prior sunitinib, a more modest PFS of 4.8 months was observed. Of course, results from the phase 2 ramucirumab experience are tempered by the absence of an independent radiographic review, which would have a bearing on both ORR and PFS.Garcia et al posit several paths forward for ramucirumab, suggesting further development as a single ...

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Anti-VEGF and VEGFR Monoclonal Antibodies in RCC

Escudier

Albigès

2014

Renal Cell Carcinoma

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Randomized Phase Ii Study of First-Line Everolimus (Eve) + bevacizumab (Bev) Versus Interferon Alfa-2a (Ifn) + bev in Patients (Pts) With Metastatic Renal Cell Carcinoma (Mrcc): Record-2

Cited by 25 publications

References 0 publications

Combination therapy regimens in the treatment of metastatic renal cell carcinoma: A review

Combination therapy regimens in the treatment of metastatic renal cell carcinoma: A review

Ramucirumab in metastatic renal cell carcinoma: The beginning or the end?

Anti-VEGF and VEGFR Monoclonal Antibodies in RCC

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