Metastatic RCC Patients Benefit From Targeted Treatment After PD-1/PD-L1 Inhibition

Targeted therapy is feasible following immune checkpoint inhibitor treatment in metastatic renal cell carcinoma

medwireNews: Use of immune checkpoint inhibitors in patients with metastatic renal cell carcinoma (mRCC) does not preclude subsequent use of targeted therapies, suggests research published in the European Journal of Cancer.

The study describes the outcomes of 56 patients who participated in clinical trials of monoclonal antibody therapy against programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) and later received vascular endothelial growth factor/Vascular endothelial growth factor receptor (VEGF/VEGFR) inhibitors (n=44) or mammalian target of rapamycin (mTOR) inhibitors (n=12).

Of note, the majority (n=47) of the patients had also used one of these targeted therapies before immune checkpoint inhibitor treatment, explain Toni Choueiri, from Harvard Medical School in Boston, Massachusetts, USA, and co-authors.

The median time to treatment failure of targeted therapy after PD-1/PD-L1 blockade was 6.9 months for patients given VEGFR Tyrosine kinase inhibitors (TKIs) and 5.7 months for those given an mTOR inhibitor, with 1-year overall survival rates of 66% and 35%, respectively.

The median overall survival for all study participants was a “very encouraging” 17.5 months, with a 1-year survival rate of 64% for patients who had a favourable or intermediate prognosis based on the International Metastatic RCC Database Consortium criteria, falling to 30% for those with a poor prognosis.

In addition, the investigator-assessed best response to targeted therapy was available for 53 patients – a partial response was achieved by 13% and stable disease by 62%, while 25% of these individuals progressed.

Finally, 23 patients went on to receive a second subsequent targeted therapy and the median time to failure of this treatment was 5.5 months.

Toni Choueiri et al write that, if clinical trials of PD-1/PD-L1 inhibitors confirm activity in mRCC, prospective trials should be designed to determine the optimal sequence of PD-1/PD-L1 and VEGF/VEGFR inhibitors and their impact on tumour biology.

The authors note that the VEGFR TKI sunitinib may have immunomodulatory properties that make it suitable as an adjunct to PD-1/PD-L1 treatment. They also hypothesise that PD-1/PD-L1 blockade may have an impact on T cells or modulate the tumour environment and impact tumour response to subsequent therapy.

The team concludes: “In a selected population, median [time to treatment failure] suggests a sustained benefit of both VEGFR TKI and mTOR inhibitors after PD-1/PD-L1 blockade.

“If immunotherapies are approved for mRCC treatment, their use in first- and second-line may challenge the frontline use of VEGF/VEGFR TKI or mTOR inhibitors and move the currently available agents to later lines in the management of advanced disease.”

Reference

Albiges L, Fay AP, Xie W, et al. Efficacy of targeted therapies after PD-1/PD-L1 blockade in metastatic renal cell carcinoma. Eur J Cancer 2015; Advance online publication 5 September. doi:10.1016/j.ejca.2015.08.017

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