Yardley Discusses Evolving Role of Nab-Paclitaxel in TNBC

Denise Yardley, MD

In the phase II tnAcity study, frontline nab-paclitaxel (Abraxane) plus carboplatin lowered the risk of progression or death by 40% compared with 2 other chemotherapy regimens in patients with metastatic triple-negative breast cancer (TNBC), according to results presented at the 2016 San Antonio Breast Cancer Symposium (SABCS).

“The Abraxane/carboplatin arm in this phase II study came out demonstrating the ideal efficacy pattern for the triple-negative population,” lead tnAcity investigator Denise A. Yardley, MD, senior investigator at the Sarah Cannon Research Institute, said in an interview with OncLive at SABCS.

The nab-paclitaxel/carboplatin doublet arm had a median progression-free survival (PFS) of 7.4 months versus 5.4 months with nab-paclitaxel/gemcitabine (HR, 0.60; 95% CI, 0.39-0.93; P = .02) and 6.0 months with gemcitabine/carboplatin (HR, 0.61; 95% CI, 0.39-0.94; P = .03). The 12-month PFS rates were 27%, 13%, and 11%, respectively.

In her interview with OncLive, Yardley discussed the tnAcity results and current role of nab-paclitaxel in TNBC, as well as the potential for using nab-paclitaxel in combination with immunotherapy in this setting.

OncLive: Could you provide an overview of the tnAcity trial?

Yardley: tnAcity is a study that is exclusively in TNBC patients. It is a first-line study looking at patients randomized to 1 of 3 arms. In the treatment arms we are looking to really evaluate the role of nab-paclitaxel, which has increasingly signaled activity in the triple-negative patient population. Gemcitabine plus carboplatin was the control arm. And then we had the doublets of gemcitabine/nab-paclitaxel and carboplatin/nab-paclitaxel.

I think it’s an exciting study because there’s such a role for doublet therapy, particularly in the triple-negative population. There’s a lot of controversy between sequential single agent or doublet therapy, but I think in the triple-negative population, really looking at a need for responses in those patients because of their aggressive relapses that are very symptomatic, they occur with a short disease-free interval, they usually are pretty scattered throughout the body so that we have both viscera and soft tissue involvement. It is a circumstance in which I, as many other investigators do, think of the double therapy, and when that comes to mind, we still have the taxanes as very active agents in cytotoxic chemotherapy for the triple-negative population.

From other previous trials, we really saw a signal for nab-paclitaxel in the triple-negative population, and so this study is looking at the partnering of nab-paclitaxel, either with carboplatin or gemcitabine, compared with the nontaxane doublet of gemcitabine and carboplatin. So through a complicated algorithm that had 5 or 6 metrics of how many cycles were completed, they were able to get a score for the treatment arm.

Certainly, I think the nab-paclitaxel/carboplatin arm in this phase II trial came out demonstrating the ideal efficacy pattern for triple-negative population. So, that’s the data on the poster that was presented at SABCS.

Now, nab-paclitaxel is also very attractive in the triple-negative population because it partners very well with immunotherapy and so now, it’s in a big phase III trial, the IMpassion130 trial (NCT02425891) with atezolizumab (Tecentriq) because it doesn't require steroid pre-medication, which may mitigate some of the benefits of immunotherapy. I think there’s a lot of excitement and we've added to that excitement with nab-paclitaxel in TNBC.

Looking ahead, what is the clinical impact that you can see this study having for patients?

It is interesting because I think cytotoxic chemotherapy still is the backbone for triple-negative patients. Now, we are in such a phase of looking at biologic therapies and combination therapy, so this may end up being the ideal backbone to add to immunotherapy. It certainly leads to future studies of partnering nab-paclitaxel, I mean we are starting to see triplets evolve with double biologics again, so we may see triplets with chemotherapy doublets and a biologic agent, too.

I think it just resonates that chemotherapy is still here to stay and still has a big role in the triple-negative population. We're trying to sort out the heterogeneity in that population so some patients may benefit from an androgen receptor agent and not require chemotherapy upfront. Others require chemotherapy for rescue response in terms of those really aggressive visceral relapses.

Are there any other questions about nab-paclitaxel that need to be addressed?

I think nab-paclitaxel has been a very welcome drug from a toxicity profile. We certainly would have loved to have embraced it in earlier lines of therapy, neo-adjuvant and adjuvant. Although, considering how well we are doing with our standard options, looking at a more favorable toxicity profile isn't always a winning FDA strategy for approving a drug. But certainly, in the metastatic setting, where patients are going to get multiple lines of therapy I think that it may have had an adjuvant component that was taxane containing.

Looking at the toxicity profile that nab-paclitaxel offers has been quite welcome in those metastatic settings, with improved neuropathy issues and depression, so again, lending itself very well to be partnered with other agents.

Is there anything else that you would like to add?

I think we saw really high response rates with nab-paclitaxel and carboplatin. It used to, traditionally be an endpoint of the trials and now we've moved more to PFS. But I think that, again, in select patients who may need rescue from their ever-growing and aggressive tumor burden, it was a nice resounding signal to see that combination being able to really afford that benefit and give another option when selecting chemotherapy for a patient with TNBC.

Yardley D, Coleman R, Conte P, et al. nab-paclitaxel + carboplatin or gemcitabine vs gemcitabine/carboplatin as first-line treatment for patients with triple-negative metastatic breast cancer: results from the randomized phase 2 portion of the tnAcity trial. Presented at: 2016 San Antonio Breast Cancer Symposium; December 6-10, 2016; San Antonio, TX. Abstract P5-15-03.