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

Elaidi, Réza‐Thierry; Harbaoui, Asma; Beuselinck, Benoît; Eymard, J-C.; Bamias, Aristotelis; Guillebon, Éléonore De; Porta, Camillo; Vano, Yann; Linassier, Claude; Debruyne, Philip R.; Gross‐Goupil, Marine; Ravaud, Alain; Aitelhaj, Meryem; Marret, Grégoire; Oudard, Stéphane

doi:10.1093/annonc/mdu552

Cited by 27 publications

(14 citation statements)

References 26 publications

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“…mOS was not reached for ORR (RC+RP), the mean OS according to DCR and ORR was 14.95 and 15.66 vs. 7.4 and 7.42 months, respectively. Our results are consistent with those of Elaidi et al who conducted a retrospective analysis of 241 m-ccRCC patients who received a first-line TKI for ≥6 months followed by a second-line TKI or mTORi, showing that patients who remained on first-line TKI between 11 and 22 months benefited from a TKI rechallenge rather than from second-line mTORi (PFS [HR≈0.5; median PFS (months): 9.4 (5.9–12.2) vs. 3.9 (3.0–5.5), p = 0.003; TTF(months): 8.0 (5.5–11.0) vs. 3.6 (3.0–4.6), p = 0.009]; Elaidi et al, 2015 ). Historically, VEGF-targeted therapy was reported to achieve higher ORR (20–30%) compared to mTOR-targeted therapy (≤ 10%), which is supported by our analysis (Grünwald et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Axitinib after Sunitinib in Metastatic Renal Cancer: Preliminary Results from Italian “Real-World” SAX Study

D’Aniello

Vitale²,

Farnesi

et al. 2016

Front. Pharmacol.

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Axitinib is an oral angiogenesis inhibitor, currently approved for treatment of metastatic renal cell carcinoma (mRCC) after failure of prior treatment with Sunitinib or cytokine. The present study is an Italian Multi-Institutional Retrospective Analysis that evaluated the outcomes of Axitinib, in second-line treatment of mRCC. The medical records of 62 patients treated with Axitinib, were retrospectively reviewed. The Progression Free Survival (PFS), the Overall Survival (OS), the Objective Response Rate (ORR), the Disease Control Rate (DCR), and the safety profile of axitinib and sunitinib–axitinib sequence, were the primary endpoint. The mPFS was 5.83 months (95% CI 3.93–7.73 months). When patients was stratified by Heng score, mPFS was 5.73, 5.83, 10.03 months according to poor, intermediate, and favorable risk group, respectively. The mOS from the start of axitinib was 13.3 months (95% CI 8.6–17.9 months); the observed ORR and DCR were 25 and 71%, respectively. When stratified patients by subgroups defined by duration of prior therapy with Sunitinib (≤ vs. >median duration), there was a statistically significant difference in mPFS with 8.9 (95% CI 4.39–13.40 months) vs. 5.46 months (95% CI 4.04–6.88 months) for patients with a median duration of Sunitinib >13.2 months. DCR and ORR to previous Sunitinib treatment was associated with longer statistically mPFS, 7.23 (95% CI 3.95–10.51 months, p = 0.01) and 8.67 (95% CI 4.0–13.33 months, p = 0.008) vs. 2.97 (95% CI 0.65–5.27 months, p = 0.01) and 2.97 months (95% CI 0.66–5.28 months, p = 0.01), respectively. Overall Axitinib at standard schedule of 5 mg bid, was well-tolerated. The most common adverse events of all grades were fatig (25.6%), hypertension (22.6%), gastro-intestinal disorders (25.9%), and hypothyroidism (16.1%). The sequence Sunitinib–Axitinib was well-tolerated without worsening in side effects, with a median OS of 34.7 months (95% CI 18.4–51.0 months). Our results are consistent with the available literature; this retrospective analysis confirms that Axitinib is effective and safe in routine clinical practice.

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Section: Discussionmentioning

confidence: 99%

Axitinib after Sunitinib in Metastatic Renal Cancer: Preliminary Results from Italian “Real-World” SAX Study

D’Aniello

Vitale²,

Farnesi

et al. 2016

Front. Pharmacol.

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“…Conversely, results of a subanalysis of the AXIS trial and a retrospective analysis have suggested that response to first-line VEGF-targeted therapy is not associated with response to second-line VEGF-targeted therapy [16,17]. A retrospective study of patients with mRCC who received a first-line VEGFR-TKI for P6 months followed by either a second VEGFR-TKI or an mTOR inhibitor reported in favour of sequential VEGFRTKIs, but the benefit was largely attributed to patients who received the first agent for 11-22 months [18]. At this time, the correlation between response to a first-line VEGF-targeted agent and second-line VEGF-targeted agent or mTOR inhibitor remains controversial.…”

Section: Discussionmentioning

confidence: 99%

Everolimus for patients with metastatic renal cell carcinoma refractory to anti-VEGF therapy: Results of a pooled analysis of non-interventional studies

Albigès

Kube

Eymard

et al. 2015

European Journal of Cancer

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“…Indeed, the m-TKI cabozantinib, which inhibits c-MET, RET, and VEGFR, showed efficacy in patients with RR-DTC refractory to at least one prior VEGFR-targeted therapy [13]. Sequential treatment with m-TKIs has also shown efficacy in patients with metastatic renal cell cancer [14,15]. Also in our present patient, sorafenib showed efficacy after she had received lenvatinib for about 3 years and she was unable to tolerate lenvatinib.…”

Section: Discussionmentioning

confidence: 66%

Successful treatment switch from lenvatinib to sorafenib in a patient with radioactive iodine-refractory differentiated thyroid cancer intolerant to lenvatinib due to severe proteinuria

et al. 2018

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Sorafenib and lenvatinib showed efficacy for patients with radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC) in pivotal phase 3 clinical trials. Although the efficacy of lenvatinib in patients who received previous treatment with multi-target kinase inhibitors (m-TKIs), including sorafenib, was reported, the efficacy of sorafenib in patients who previously received lenvatinib remains unknown. A 75-year-old woman diagnosed as RAI-refractory poorly differentiated carcinoma with multiple lung metastases and started treatment with lenvatinib. She continued to receive lenvatinib but with repeated dose interruptions and reductions due to continuous proteinuria. Because of severe and persistent proteinuria as well as newly developed renal impairment, lenvatinib was suspended after two years of treatment. After the 7-month suspension, her proteinuria and renal impairment were partially improved, but her lung metastases progressed. Because she was unable to tolerate previous treatment with lenvatinib, sorafenib was started. At 7 months of treatment with sorafenib, her lung metastases shrank and she could continue sorafenib without exacerbation of proteinuria or renal impairment. This case may suggest that sorafenib does not exacerbate the proteinuria or renal impairment induced by lenvatinib, and may be an effective treatment option for RAI-refractory DTC patients who are unable to tolerate lenvatinib.

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

Abstract: m-ccRCC patients who remained on first-line TKI between 11 and 22 months benefited from a TKI rechallenge rather than from second-line mTORi.

Cited by 27 publications

References 26 publications

Axitinib after Sunitinib in Metastatic Renal Cancer: Preliminary Results from Italian “Real-World” SAX Study

Axitinib after Sunitinib in Metastatic Renal Cancer: Preliminary Results from Italian “Real-World” SAX Study

Everolimus for patients with metastatic renal cell carcinoma refractory to anti-VEGF therapy: Results of a pooled analysis of non-interventional studies

Successful treatment switch from lenvatinib to sorafenib in a patient with radioactive iodine-refractory differentiated thyroid cancer intolerant to lenvatinib due to severe proteinuria

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