We loved the Sarcoma Exchange!

By Suzie Siegel

The Sarcoma Exchange proved so successful that even before it ended, survivors were asking about the next one. 

“We were so encouraged by the outpouring of participation by the sarcoma patient, caregiver and survivor community. We had 147 attendees, but many more expressed that they wanted to attend,” said Alyssa O’Driscoll, executive director of the Sarcoma Alliance. “We’re planning to make this a regular part of our programming should funding continue.” 

The Alliance, founded in 1999, is an international nonprofit dedicated to the education, guidance and support of people affected by sarcoma. Although survivors and families meet each other at Alliance events, this the first time it has held a patient-education conference. 

The conference was July 20-22 in Atlanta. Patients and caregivers came from 29 states and represented 21 subtypes. The patient who had survived the longest was Susie Wright of Cairo, GA, who was diagnosed with synovial sarcoma 48 years ago. The subtype with the most survivors in attendance was leiomyosarcoma (LMS).  

LMS survivor Sharee Whitmer (left) and Lisa Kessler, whose husband survived LMS, but their son did not.    

"The information gleaned from the sarcoma oncologists and researchers empowered me in a way that really let me feel I have some options that I have not exhausted," said Sharee Whitmer of Madisonville, VA, an LMS survivor. She came with her husband and their therapy dog, Stella. "It reassured us that the sarcoma oncologist and team that I am with now are staying well-informed and that I am indeed in good hands. And when and if the time comes to move on and find another team, I have many other choices.

"For us to have some idea of how up-do-date our care and our options, including trials, really are, it is imperative to attend conferences aimed at educating and empowering patients. Not everyone is seen at a large sarcoma center.

"The BIG take away from the conference for us was to really be able to connect in person with other sarcoma patients and their caregivers that we have met through online support groups. And during the conference to be able to meet so many more that we would not have met if it were not for attending the conference. Knowledge is incredibly valuable for patients like us, and having the opportunity to exchange our experiences while enduring this diagnosis and the treatments that follow are invaluable."  

Mary Prince, Lea Custer and me

Mary Prince of Portland, OR, came from the farthest away. Her sister, another LMS survivor, lives in Murrayville, GA. 

“Attending this wonderful event with my longterm-thriver/ BFF / sister, Lea Custer, was the highlight of the year for me. Meeting other LMS survivors and meeting all the wonderful medical professionals and hearing what's coming up on the horizon made it an incredible conference. Love was everywhere; you could feel it!" Mary said. "A special shout out to Dr. Gina D'Amato, Lea's primary sarcoma physician, who made it all happen.”  

Dr. D’Amato, a Sarcoma Alliance board member, practices at Northside Hospital’s Cancer Institute in Atlanta. She’s grateful that sarcoma specialists from across the South volunteered to speak, along with her colleagues from Northside.

The medical oncologists who spoke were Dr. Robert Benjamin and Dr. Shreyaskumar Patel from MD Anderson Cancer Center in Houston, Dr. Jonathan Trent from the Sylvester Cancer Center in Miami, and Dr. Richard Riedel from Duke Cancer Institute in Durham, N.C. Dr. Scott Davidson, a surgical oncologist, and Dr. Hamilton Williams, a radiation oncologist, attended from Northside.

Breakout sessions covered patients in treatment, survivors and caregivers.

Amanda Smith with the late Roger Henderson

"Never quit the fight. That was my mindset," said Amanda Smith of Havelock, NC, who facilitated the caregiver section. She lost her boyfriend, Roger Henderson, to chondrosarcoma. An LPN, she's in school to become an RN. 

Sarcoma Alliance board member Marites Tullius, a nurse practitioner, spoke on palliative care. From Northside, registered dietitian Rebecca Perez spoke on nutrition; social worker Myra Bazell, stress management; RN Debbie Bickes, patient navigation; and occupational therapist Melora Rennie, exercise and fatigue.

Osteosarcoma survivor Woody Roseland, whose "S#!%Cancer Patients Say” brought knowing laughs, entertained us one afternoon. That night, hypnotist Ricky Kalmon evoked a great deal of silliness from his targets.  

Sponsors were drug companies Lilly, Eisai, Ignyta, Novartis, Immune Design and Epizyme as well as  Northside Hospital’s Sarcoma Program. Thanks to them, we had free rooms at the Marriott Perimeter Center Hotel and delicious meals. 

  

Presentations from the conference are posted here: https://sarcomaalliance.org/event/sarcoma-exchange-2018/ Here are a few tidbits:

Dr. D'Amato with Dr. Benjamin

"Stage 4 has a bad connotation. I don't even use it in clinic,” Dr. D’Amato said. The problem with "stage 4" or "terminal" is that these labels include people whose sarcoma has spread far and wide as well as those with oligometastatic disease, which means they have only a few small tumors in one or two distant locations. Some people think "stage 4" or "terminal" means they are going to die soon. They may decline treatment that could help them live longer.

Dr. D’Amato noted that "remission" applies to people who no longer have any evidence of sarcoma after their initial treatment. The term for people who have no evidence of disease after they have been treated for metastatic sarcoma is NED. For example, my original leiomyosarcoma was 2C. Soon after, one small lung metastasis was found; 18 months later another appeared. Thanks to radiation, chemo and surgery, I’m NED from oligometastatic disease.

Dr. Riedel

“When you’re educated, you’re empowered,” said Dr. Riedel, who spoke on immunotherapy. “The future is bright.” 

Don’t let community doctors take you off of a drug just because your tumors aren’t shrinking, he said. His mantra is: “Stable disease is a good thing.”

“Patients want their sarcomas to shrink and disappear, but doctors are happy with stability,” Dr. D’Amato stressed. Sarcoma specialists may try new treatments only if tumors start to grow. 

Some times the tumor stays the same, or even looks larger, but is actually dead after treatment. Some tumors shrink, but not enough to meet the definition of shrinkage in clinical trials. 

Researchers refer to “progression-free survival” (PFS) when tumors stay stable. Some people don’t think the FDA should approve drugs based on stability. They want clinical trials to prove that the people who got the new drug lived longer, which is called “overall survival” (OS). 

Dr. Benjamin thinks PFS can be a good sign that a drug is working. The problem with OS is that it measures  things that weren’t part of the clinical trial, he said. For example, the clinical trial on doxorubicin (adriamycin) + olaratumab (Lartruvo) compared it with dox by itself. But people who got olara may have gone on to get better treatment, improving their survival.  That’s why MD Anderson is doing a clinical trial to compare dox + olara to the older combination of dox + ifosfamide.

Dr. Patel

Dox + ifos is a common treatment for sarcomas, and some community doctors may try to treat all sarcomas with it, Dr. Patel said. They shouldn’t, he added. They need to look at each subtype individually because some, such as alveolar soft part sarcoma (ASPS), don’t respond to this chemo combo. 

        

Because immunotherapy is in the news, he spends a lot of time educating patients on why chemo may be better than immunotherapy for their particular sarcomas. He also discusses the advantages of a clinical trial vs. standard treatment.

“Patients must have information to make a decision,” Dr. Patel said.

A variation on doxorubicin, called aldoxorubicin, “clearly has less cardiac toxicity. It’s a very good drug,” Dr. Benjamin said. We await the results of clinical trials and a decision by the FDA. 

Dr. Trent

Dr. Trent joked about the crazy names that pathologists give to sarcoma subtypes, such as dermatofibrosarcoma protuberans (DFSP). Nevertheless, medical oncologists like Dr. Trent greatly respect sarcoma pathologists. You can’t get the best treatment without an accurate diagnosis. 

For example, most sarcoma cells look like spindles under the microscope, Dr. Benjamin said. If pathologists cannot identify the tumor’s subtype, they may use the catch-all term of “spindle-cell sarcoma.” 

Instead of taking a tissue sample, some doctors are looking at tumors’ DNA circulating in the bloodstream (called ctDNA). They want to see which treatments are working and which might work for the patient in the future. Although these “liquid biopsies” are still experimental, Dr. Trent said: 

“This is what the future is.”

After Yondelis, which drugs may get OK'ed next?

By Suzie Siegel

Many of us have waited years for the FDA to approve trabectedin (Yondelis) for soft-tissue sarcoma.

Dr. Gina D'Amato

“I was ready to march on Washington if it didn't get approved!” Dr. Gina D’Amato said Friday, after the FDA approved trabectedin for patients with liposarcoma and leiomyosarcoma who have already tried an anthracycline, such as doxorubicin, but have an inoperable tumor or one that has spread. Dr. D’Amato, a board member of the Sarcoma Alliance, treats patients at Georgia Cancer Specialists in Atlanta.

For metastatic leiomyosarcoma, Atara Weinstein had three surgeries and more than 35 rounds of chemotherapy with six different drugs before starting a clinical trial for trabectedin in February.

“I have been fortunate that with Yondelis I've had some stability these past few months. And it will be easier, all round, to get the drug without the hassles and red tape of a clinical trial protocol,” she said. “Spiritually, getting this approved is a big affirmation to never give up hope.

“Until a cure is discovered, chemo can be a good way to stay ahead of the rampage, and even though side effects are definitely a consideration, they can absolutely be managed for quality of life.”

Because sarcomas are rare, they get less money for research, companies have less interest in investing in them, and enrolling enough patients in clinical trials is difficult.

The FDA has approved only six other chemotherapy drugs for soft-tissue sarcoma: Dactinomycin in 1964 for rhabdomyosarcoma, doxorubicin (Adriamycin) in 1973, imatinib (Gleevec) for gastrointestinal stromal tumor (GIST) in 2001, sunitinib (Sutent) for GIST in 2006, pazopanib (Votrient) in 2012 and regorafenib (Stivarga) for GIST in 2013. Doxorubicin and pazopanib are the only ones commonly used in different types of sarcoma.

Some drugs approved for other cancers also help sarcoma patients. Because the FDA hasn’t approved them for sarcoma, however, doctors give them “off-label.” Examples are ifosfamide (Ifex), dacarbazine (DTIC), gemcitabine (Gemzar) and docetaxel (Taxotere).

Dr. Breelyn Wilky

Some doctors may try trabectedin off-label for sarcoma subtypes other than the two for which it got approval. One problem with this practice is that a person’s insurance may not pay for an off-label drug, noted Dr. Breelyn Wilky, assistant professor in the sarcoma program at the Sylvester Comprehensive Cancer Center in Miami.

Scientists and physicians have been working on trabectedin for more than 15 years, back when it was called ET-743. It was approved in Europe in 2007 and is widely used there. U.S. sarcoma doctors have grumbled over the length of time it has taken for FDA approval. This year, a phase III trial confirmed that the drug can keep leiomyosarcoma and liposarcoma from growing and spreading longer than can dacarbazine. The trial couldn’t prove patients live longer on trabectedin, perhaps because of the trial design.

Clinical trials are broken into three phases. The latest trabectedin trial may have succeeded because it focused on the two types of sarcoma that have gotten the most benefit. In the past, the FDA has hesitated to approve drugs that couldn’t be proven to significantly extend patients’ lives. In 2012, however, it didn’t require that proof for pazopanib. It approved the drug for keeping patients stable longer – just like trabectedin.

Dr. Jonathan Trent, co-director of the Musculoskeletal Center at the Sylvester cancer center, said he wants to stress how effective trabectedin is. “We have had metastatic patients in regression for more than two years.”

Trabectedin was synthesized from a sea squirt. The next sarcoma drug that may win approval also comes from the ocean. Eribulin (Halaven) was derived from sea sponges. This month, the FDA gave it Priority Review status, which means the FDA is expected to make a decision within six months. In a phase III clinical trial, eribulin helped patients with liposarcoma and leiomyosarcoma live longer, compared with dacarbazine. The FDA has already approved eribulin for breast cancer.

The FDA has granted Fast Track status to evofosfamide, formerly called TH-302. This designation speeds up the review process, but not as quickly as Priority Review does. Results from phase III studies are expected this year.

There is hope evofosfamide will be safer than its older cousin, ifosfamide. Dr. Trent said ifosfamide can be more dangerous than some drugs because patients have to be monitored more closely, and some oncologists weren’t trained in sarcoma centers that used it regularly. He said he uses higher doses of ifosfamide than some other doctors because he knows how to monitor it.

With some chemos, more is better, he said. For example, the higher the dose of doxorubicin and ifosfamide, the higher the percentage of patients who benefit.

Results of a phase IIb study of aldoxorubicin were published last month, saying it kept sarcoma stable longer than its cousin, doxorubicin. Because of the danger of damaging the heart, patients are limited on how much doxorubicin they can receive. So far, patients have been getting much more aldoxorubicin without hurting their hearts. A phase III clinical trial is underway.

Dr. Daniel Rushing

In the past, a common chemo combination was dacarbazine, doxorubicin and ifosfamide. Use of dacarbazine peaked in 1993, said Dr. Daniel Rushing, professor of clinical medicine at Indiana University in Indianapolis. It fell out of favor because of nausea and vomiting, he said, but it has made a comeback in recent years as new drugs have better controlled the side effects.

Regorafenib is in a phase II clinical trial for liposarcoma and bone sarcomas. But Dr. Trent said it’s unclear whether it will be approved – the FDA has issued a black-box warning for its potential to damage the liver.

A phase II study of masitinib found it superior to sunitinib for GIST. “I think masitinib could be the next super-Gleevec,” Dr. Wilky said. Another phase II study is looking at the addition of MORAb-004 to gemcitabine + docetaxel.

A phase Ib/II trial this year found olaratumab helped sarcoma patients (a third had leiomyosarcoma) live longer when the drug was added to doxorubicin, as opposed to doxorubicin only. The FDA gave it Breakthrough Therapy Designation.

In phase Ib/II trials, TRC105 + pazopanib got complete remission for two patients with angiosarcoma.

Dr. Jonathan Trent

It’s too early to tell whether AG-120, in a phase I clinical trial for chondrosarcoma, will prove effective, Dr. Trent said. But he describes a patient whose cancer was growing before the trial and now has been stable for nine months. “Is that success? I think so.”

The FDA has approved pembrolizumab (Keytruda) and nivolumab (Opdivo) for other cancers, and they are now in phase II trials for sarcoma. A clinical trial of avelumab may open in 2017. These drugs are anti-PD1 antibodies, a form of immunotherapy. Immunotherapy drugs help the body recognize and attack cancer cells. Immunotherapy has gotten great acclaim.

“Research is exploding,” Dr. Wilky said, adding that alveolar soft-part, synovial and clear cell sarcomas may respond well. In general, however, she sees sarcoma doctors becoming less enthusiastic.

“One issue is that the sarcoma may be growing quickly while the immunotherapy takes longer to work. Another issue is getting the drug into tumors that no longer have a big blood supply. Side effects also can be very dangerous.

“Single-agent anti-PD1 is not going to be enough to cure people.” Immunotherapy will probably need to be combined with other drugs, Dr. Wilky said. Next year, she hopes to open a trial with pembrolizumab + axitinib, which is similar to pazopanib.

PD1 is a checkpoint that keeps the immune system from eating cancers. Ipilimumab (Yervoy) targets another checkpoint, CTLA-4, while palbociclib (Ibrance) inhibits CDK4 and CDK6. The FDA has approved both for other cancers. A phase II trial of palbociclib in liposarcoma had promising results, Dr. Wilky said. She also is interested in the phase I/II clinical trial for ipilimumab + nivolumab.

She recalls how clinical trials were once the last resort for patients. That’s no longer the case, she said, because doctors can better predict which patients will benefit from an experimental drug. “You should consider going on a clinical trial early in your treatment.”

I got a chance to talk to Drs. Wilky and Trent at a patient education conference last month at the Sylvester cancer center, co-sponsored by the Sarcoma Foundation of America. Dr. Trent said it was the first conference for sarcoma patients in South Florida.

For more information, check out Dr. Wilky’s blog post on clinical trials: http://breelynwilkymd.com/2015/10/17/clinical-trials-what-you-should-know-to-make-an-informed-choice-about-your-therapy/ The Sarcoma Alliance has a page on clinical trials: http://sarcomaalliance.org/what-you-need-to-know/clinical-trials/ The Sarcoma Alliance for Research through Collaboration lists its trials: http://sarctrials.org/sarc-clinical-trials And the Sarcoma Foundation of America can help you find a trial: http://www.curesarcoma.org/patient-resources/sarcoma-clinical-trials/