CTA: What does that mean for optimal treatment duration or treatment beyond radiologic progression?

Dr Iacovelli: These are 2 topics of interest for clinicians involved in the management of kidney cancer. We have no evidence for treatment discontinuation…treatment should be continued until progression.

In my opinion, data supporting the treatment beyond progression should be considered as preliminary evidence and have to be confirmed in prospective studies; they should be limited to patients with good clinical conditions and no symptoms related to the disease.

Bearing in mind the availability of alternative therapies that may improve survival in kidney cancer (eg, cabozantinib), this should be preferred if not previously prescribed.

CTA: What about dual immune-checkpoint inhibition strategies? Your team has spotlighted the possibility of simultaneously targeting PD-1 and CTLA-4 in RCC. What does the current evidence look like?

Dr Iacovelli: Exciting preliminary results about the co-inhibition of PD-1 and CTLA-4 were presented last year at the European Society for Medical Oncology (ESMO) Congress.3

Now, there are clinical trials ongoing with the combination of nivolumab and ipilimumab in kidney cancer both for patients with advanced or metastatic disease and in patients with no evidence of metastasis.

CTA: How might a patient’s gut microbiome affect immune checkpoint inhibitors or other immunotherapy agents’ antitumor activity?

Dr Iacovelli: This year at the Genitourinary Cancers Symposium it was reported that activity of immunotherapy on tumors is reduced in patients that received antibiotics in weeks before the beginning of anticancer therapy.4

This evidence suggested a correlation between the gut microbiome and the immune system and with the efficacy of immunotherapy, though these results need to be confirmed in a larger series of patients.

Reference

  1. Ciccarese C, Di Nunno V, Iacovelli R, Massari F. Future perspectives for personalized immunotherapy in renal cell carcinoma. Exp Opin Biol Ther. 2017 Jun 7. doi: 10.1080/14712598.2017.1339030 [Epub ahead of print]
  2. Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373(19):1803-13.
  3. Hammers H, Plimack ER, Infante JR, et al. Updated results from a phase I study of nivolumab (Nivo) in combination with ipilimumab (Ipi) in metastatic renal cell carcinoma (mRCC): the CheckMate 016 study. Ann Oncol. 2016;27(suppl; 1062P). doi: 10.1093/annonc/mdw378.16
  4. Derosa L, Routy B, Enot D, et al. Impact of antibiotics on outcome in patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors. J Clin Oncol. 2017;35(suppl; abstr 462).