Following a thumbs-up for its first-of-a-kind MarginProbe breast cancer detection device last week, Dune Medical Devices is promising to work closely with FDA to complete the approval process and plans an immediate U.S. launch should the watchdog agency give it a green light.
The FDA’s general & plastic surgery devices committee met June 21 in Gaithersburg, Md., to mull whether the device, which uses electromagnetic waves to identify possibly cancerous tissue on the edges of a breast tumor, ought to be approved for the U.S. market.
The panel voted 11-0 that the device is safe, 8-1 with 2 abstentions that it is effective and 10-1 that its benefits outweigh its risks.
During a public hearing prior to the vote, speakers expressed unanimous support for approval of the MarginProbe device.
"We are very pleased with the panel’s positive decision on the MarginProbe system for use in the U.S.," Dune CEO Dan Levangie said in prepared remarks. "We believe that the MarginProbe System will give surgeons a powerful tool in their fight against breast cancer and provide women a substantially better chance of avoiding additional surgeries."
The MarginProbe device, which won CE Mark approval in the European Union in 2006, is Framingham, Mass.-based Dune Medical’s first commercial product.
The company submitted a pre-market approval application in April 2011, based on data from a 600-patient pivotal study conducted primarily in the U.S.
The company cites studies showing that the device’s detection of "positive margins" – the cancer found at the edges of excised breast tissue – contributes to a 50% reduction in additional procedures to remove residual cancer.
The data show that "between 30%-60% of women who undergo breast conservation surgery have to undergo additional surgeries because doctors fail to achieve negative margins during the first surgery," according to Dune Medical.
Several panelists recommended that the company re-crunch some of the data to better address efficacy questions about the device when compared to the standard of care. Other panelists noted that there really is no standard operating procedure for performing lumpectomies.
"Surgery is a little bit like painting," said Dr. Benjamin Anderson of the University of Washington. "We all develop our own techniques, but you need to design a study that will get you through the fact that we are never going to do it the same, it’s the outcome that we care about. … I thought that the beauty of this approach was basically the surgeons did it the way they do it, with or without the probe. That’s the idea of a randomized trial.
"These endpoints, you’re right, there’s a lot of statistical questions, but at the end of the day what the patients care about is, ‘Am I going back to the operating room or am I not?’ And that to me is the bottom line. I think we have to consider the clinical endpoints as the major decider."
Suggestions from panelists
Overall, panelists agreed that using complete surgical resection to intraoperatively assess positive margins and show superiority as the sole primary endpoint in the clinical trial provided "weak and somewhat confusing" efficacy data.
However, the company already has all the data it needs to do a re-analysis using 2 other co-primary endpoints: Non-randomness test and normalized tissue volume. That means Dune won’t need to run a new pivotal trial, panelists noted.
"If FDA and the sponsor were to work together to re-crunch the numbers a little bit, the 3 co-primary endpoints would probably adequately address clinical effectiveness," said panel chairman Dr. Joseph LoCicero III of SUNY Downstate.
And the FDA noted that MarginProbe significantly increased surgeons’ sensitivity to intraoperatively identify additional tissue that should be shaved over the standard of care, but reduced specificity in comparison, and asked panelists to comment on whether size of the resection should be taken into account.
"We want both sensitivity and specificity," LoCicero said. "Surgeons are tired of having patients come back to the OR."
While removing all cancerous tissue is of the highest concern, patients and surgeons are also interested in achieving good cosmetic outcomes for breast lumpectomies. Some patients may return to the operating room to fix a poor cosmetic result. To confound this point, while some surgeons who are experienced with oncoplastic techniques can make a larger resection look good, others are unable to do so, panelists noted.
"What’s acceptable for resectable volume is getting the cancer out," LoCicero said. "The minimum benefit would be that if we could prove that we were resecting as minimal as possible to get all the cancer and that the probe helped us do that. In terms of risk, it didn’t seem like the panel had specific concerns about risk."
Finally, panelists recommended that cosmetic appearance after resection be used as an endpoint in post-market studies and should be addressed on a validated scale.
"I think the No. 1 worry about FDA approval is that sometimes companies use this as a stamp for marketing and run with the ball, and I don’t get the sense that that’s the nature of this company," Anderson said. "The research that follows is really important. We want to answer the questions that you’ve so nicely raised."
The nod from the advisory panel doesn’t assure approval of MarginProbe, but the FDA usually follows its panels’ guidance.