The efficacy of VEGFR TKI therapy after progression on immune combination therapy in metastatic renal cell carcinoma

Barata, Pedro C.; Liaño, Alfonso Gómez de; Mendiratta, Prateek; Crolley, Valerie; Szabados, Bernadett; Morrison, Laura; Wood, Laura S.; Allman, Kimberly D; Tyler, Allison; Martin, Allison; Gilligan, Timothy D.; Grivas, Petros; Ornstein, Moshe Chaim; García, Jorge A.; Powles, Thomas; Rini, Brian I.

doi:10.1038/s41416-018-0104-z

Cited by 45 publications

(39 citation statements)

References 18 publications

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“…In one study, 20/56 received axitinib after progression on an ICI with a median TTF of 10.0 (0.2+, 19.3), one-year survival rate of 69 % (34,88), and ORR of 16 % [25]. Similarly, a second study reported 14/28 patients who received axitinib after progression on an ICI with a median PFS of 6.4 months (4.7-8.1) and an ORR of 29% [24]. In patients progressing on nivolumab and ipilimumab, the median PFS with subsequent axitinib treatment was 7 months (95% CI, 5-NR) [26].…”

Section: Axitinibmentioning

confidence: 98%

“…Few retrospective analyses have evaluated the efficacy of targeted treatment in patients who have disease progression on ICI-based therapy [23][24][25]. The ORR ranged from 13-29% and PFS or Time to Treatment Failure (TTF) ranged from 6.4-6.6 months.…”

Section: What Comes After Iomentioning

confidence: 99%

“…In another retrospective study of VEGF TKIs after progression on ICI, 3/28 patients received cabozantinib after progression on an ICI with 33% ORR [24].…”

Section: Cabozantinibmentioning

confidence: 99%

“…Best response was SD in 9 patients whereas PD occurred in the remaining 5 patients. On the other hand, Barata et al [24] reported 7 of 28 patients who received pazopanib after progression on an ICI with a median PFS of 5.6 months (1.2-10.0) and ORR of 43%.…”

Section: Pazopanibmentioning

confidence: 99%

“…No prospective data regarding its use in the post ICI space exists. A retrospective study [24] has reported 4 patients treated with sunitinib with a median PFS of 2.9 (0.0-7.6). No responses were observed.…”

Section: Sunitinibmentioning

confidence: 99%

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What Comes After Immuno-Oncology Therapy for Kidney Cancer?

Zahoor

Duddalwar

D'souza

et al. 2019

KCA

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The treatment landscape of advanced renal cell carcinoma (RCC) is rapidly evolving. Immune checkpoint inhibitors (ICI) have now become the preferred first line treatment with the approval of nivolumab and ipilimumab combination in intermediate to poor risk patients. Combination/s of ICI with vascular endothelial growth factor (VEGF) inhibitors will also be approved in future. The optimal treatment of patients who progress on ICI-based therapies is not well defined as of yet. In this review, we discuss the data regarding various treatment options available in this space, their limitations, and also provide our opinion regarding treatment selection.

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Section: Axitinibmentioning

confidence: 98%

Section: What Comes After Iomentioning

confidence: 99%

“…In another retrospective study of VEGF TKIs after progression on ICI, 3/28 patients received cabozantinib after progression on an ICI with 33% ORR [24].…”

Section: Cabozantinibmentioning

confidence: 99%

Section: Pazopanibmentioning

confidence: 99%

Section: Sunitinibmentioning

confidence: 99%

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What Comes After Immuno-Oncology Therapy for Kidney Cancer?

Zahoor

Duddalwar

D'souza

et al. 2019

KCA

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Patterns and outcomes of subsequent therapy after immune checkpoint inhibitor discontinuation in HCC

et al. 2022

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The availability of immune checkpoint inhibitors (ICIs) for the management of advanced hepatocellular cancer (HCC) has changed the treatment paradigm. There are emerging questions regarding the efficacy of subsequent anticancer therapies. The primary aim of this retrospective, multicenter study was to examine the types of anticancer treatment received after ICIs and to assess the impact on post‐ICI survival. We established an international consortium of 11 tertiary‐care referral centers located in the USA (n = 249), Europe (n = 74), and Asia (n = 97), and described patterns of care following ICI therapy. The impact of subsequent therapy on overall survival (OS) was estimated using the Kaplan–Meier method and presented with a 95% confidence interval (CI). A total of 420 patients were treated with ICIs for advanced HCC after one line of systemic therapy (n = 371, 88.8%): 31 (8.8%) had died, 152 (36.2%) received best supportive care (BSC) following ICIs, and 163 patients (38.8%) received subsequent anticancer therapy. Tyrosine kinase inhibitors (TKIs, n = 132, 80.9%), in particular sorafenib (n = 49, 30.0%), were the most common post‐ICI therapy followed by external beam radiotherapy (n = 28, 17.2%), further immunotherapy (n = 21, 12.9%), locoregional therapy (n = 23, 14.1%), chemotherapy (n = 9, 5.5%), and surgery (n = 6, 3.6%). Receipt of post‐ICI therapy was associated with longer median OS compared with those who had received BSC (12.1 vs. 3.3 months; hazard ratio [HR]: 0.4 (95% CI: 2.7–5.0). No difference in OS was noted in those patients who received TKI before ICIs compared with those who received ICIs followed by TKI. Conclusion: Post‐ICI therapy is associated with OS in excess of 12 months, suggesting a role for therapeutic sequencing. OS from TKI therapy was similar to that reported in registration studies, suggesting preserved efficacy following ICIs.

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Recurrent multiple liver metastases of clear cell renal cell carcinoma with a significant response to sunitinib after nivolumab treatment

et al. 2022

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Introduction A case of multiple liver metastases of clear cell RCC with a significant response to sunitinib as the fifth line after nivolumab is reported. Case presentation The patient was a 65‐year‐old man who underwent open nephrectomy for RCC. After the nephrectomy, he had recurrences several times, and metastasectomy had been performed for each recurrence. At 13 years after the nephrectomy, multiple liver, and lung metastases appeared. The treatment was switched to axitinib, followed by cabozantinib, then nivolumab. The best response was PR, SD, and PD for these three drugs, and treatment duration was 14, 3, and 3 months, respectively. As the fifth line, sunitinib was administered, with significant shrinkage of the multiple liver metastases, and PR has been maintained for 34 months. Conclusion Sunitinib after an IO‐drug showed a significant effect in spite of only slight efficacy with other VEGFR‐TKIs, which may have occurred through the alteration of the immunological microenvironment.

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The efficacy of VEGFR TKI therapy after progression on immune combination therapy in metastatic renal cell carcinoma

Abstract: VEGFR TKIs have clinical activity in mRCC refractory to IC therapy, possibly impacted by the mechanism of prior combination therapy.

Cited by 45 publications

References 18 publications

What Comes After Immuno-Oncology Therapy for Kidney Cancer?

What Comes After Immuno-Oncology Therapy for Kidney Cancer?

Patterns and outcomes of subsequent therapy after immune checkpoint inhibitor discontinuation in HCC

Recurrent multiple liver metastases of clear cell renal cell carcinoma with a significant response to sunitinib after nivolumab treatment

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