Expert Highlights Efficacy of Avelumab in Early Lines of Therapy for Advanced RCC

Ulka Vaishampayan, MD

Ulka Vaishampayan, MD

According to findings from the phase Ib multicohort JAVELIN Solid Tumor trial, avelumab (Bavencio) demonstrated efficacy as a monotherapy in both the first- and second-line setting for patients with advanced renal cell carcinoma (RCC).

The PD-L1 inhibitor demonstrated an approximately 20% response rate while about 75% of patients had tumor shrinkage or stabilization. The duration of response was about 9 months with a 1-year remission rate seen in majority of patients.

In an interview withTargeted Oncology, Ulka Vaishampayan, MD, professor of Oncology at Wayne State University, Karmanos Cancer Institute, discussed the data reported from the phase Ib study at the ESMO 2018 Congress and addressed how these data will affect the treatment landscape for patients with advanced RCC.

TARGETED ONCOLOGY:Can you provide an overview of the results you presented?

Vaishampayan:Kidney cancer is an immune-responsive disease and the programmed death pathway has shown tremendous promise and efficacy in advanced kidney cancer. The PD-L1 inhibitor avelumab was evaluated starting with a phase I trial trying to establish safety and then expanding to multiple cohorts, 1 of which included both frontline and second-line RCC cohorts. Within that patient population, avelumab did show clinical efficacy. The safety was no different than what had been noted before with a fairly tolerable toxicity profile, but the efficacy was remarkable, with about a 20%-plus response rate. [Also], about 75% of the patients had tumor shrinkage or stabilization and did not show progression on the therapy.

The duration of response was also pretty promising, with a median of about 9 months and a 1-year remission rate of progression-free survival in about two-thirds of the patients. In the second-line setting, [there were] pretty similar results. The efficacy was maintained and seen, and it was about 10% or so of actual objective response rate. Again, the chances of stable disease, if you include those, then the overall tumor shrinkage rate was about 75%, even in the second-line setting.

Given this promising efficacy, PD-L1 subsets were tested, looking at the 1% cutoff to see if PD-1-positive versus negative would make a difference. Interestingly, it did not seem to have an impact on the overall efficacy of this compound.

TARGETED ONCOLOGY:How do you differentiate between patients who should receive this as a monotherapy or combination in the frontline?

Vaishampayan:I think at this point, only single-agent has been evaluated extensively in advanced kidney cancer. The only combination that had been evaluated until this meeting, frankly, is the ipilimumab (Yervoy) and nivolumab (Opdivo) combination, so combining 2 different immunotherapies, both of which are immune checkpoint inhibitors.

We had noted in the phase II trial of axitinib and avelumab tremendous improvement in response rates from the 20% range or so as I reported for the single-agent to about the 68% or 70% range with the combination. There is clearly both preclinical and clinical synergy established between an anti-VEGF TKI like axitinib and nivolumab therapy.

Now, of course, with the results of the phase III trial that showed remarkably improved efficacy as compared to single-agent sunitinib therapy. I think the results speak for itself in terms of improvement in progression-free survival and potentially overall survival, although the results are not mature yet.

TARGETED ONCOLOGY:What’s next for avelumabtherapy in RCC?

Vaishampayan:I think at this point, to explore it further as a single agent would not make sense in RCC because with the relatively well-tolerated toxicity profile of the combination and the improvement in efficacy, I think that moving forward, chances are majority of the kidney cancer patients with metastatic disease are likely to get the combination as an upfront therapy. It could be potentially explored in the third-line or fourth-line, so the pretreated setting. There is still remarkable efficacy noted for avelumab, and for patients who are treated upfront with the anti-VEGF, avelumab maintains efficacy in that setting.

TARGETED ONCOLOGY:In this age of immunotherapy, do you still see targeted therapies, chemotherapy, or other older methods remaining in this treatment landscape?

Vaishampayan:I think the field is headed toward combinations. First, we thought that combining the 2 immune checkpoint therapies would probably be the way to go, but now we are realizing, especially with the axitinib and avelumab showing improved efficacy, that the combination of a TKI and an immune therapy makes the most sense and maintains relatively well-tolerated toxicity in this patient population.

TARGETED ONCOLOGY:What other data has come out recently that you find significant in the field?

Vaishampayan:Some of the other exciting advances that were reported in kidney cancer were about biomarker testing and if they could have predictive value for sunitinib efficacy. The problem is that, unfortunately, single-agent sunitinib has been shown to be inferior to a number of other regimens now, so using it in the frontline setting is going to fade away. Still, whether that same biomarker panel holds predictive efficacy for other TKIs remains to be seen and exploring in that direction would be reasonable.