Yoav Hadas, 51, worked as a pastry chef in Israel for twenty years until he was diagnosed with stage IV pancreatic cancer in April 2015. His cancer was metastatic, spreading to other organs in his body, and lowering his five-year-survival rate to three percent. He was given between six months and a year left to live.
When he told his wife and three boys about his diagnosis, he “decided to do everything – to try everything – to change this,” Hadas said in a phone interview with NoCamels. Hadas and his wife were “looking for something outside the box because regular treatment was not promising for [his] condition.”
They came across Dr.Talia Golan, an Israeli oncologist as well as lead researcher of the Pancreas Cancer Olaparib Ongoing (POLO) Clinical Trial at the Sheba Medical Center, working specifically with patients with advanced stages of pancreatic cancer as well as a BRCA 1 or 2 germline mutation.
BRCA1 & 2 are tumor suppressor genes, meaning that those with the deleterious mutation have a higher lifetime risk of developing cancer. The gene is predominantly linked to breast and ovarian cancer, but several studies name pancreatic cancer the third most common cancer associated with these mutations. Notably, a large, disproportionate number of Jews of European origin, also known as Ashkenazi Jews, have these mutations.
Among patients with pancreatic cancer, only four to seven percent have this gene variation, so Dr. Golan’s clinical trial team looked for participants from across the world.
“This was a huge global and collaborative effort. It was difficult to find the patients with this specific mutation,” Dr. Golan describes in an email interview with NoCamels.
To participate in Dr. Golan’s study, Hadas had to do eight rounds of chemotherapy over 16 consecutive weeks, as well as a multitude of genetic and organ function tests.
Dr. Golan’s study, in collaboration with Astrazeneca and MSD (Merck), two of the world’s largest biopharmaceutical companies, uses a PARP inhibitor called Lynparza™, the trade name for the biological agent olaparib. The drug blocks the production of Poly ADP-ribose Polymerase (PARP), a protein that repairs DNA in tumor cells.
The study, published for the first time in the New England Journal of Medicine in June, explains, “PARP inhibitors cause an accumulation of DNA damage and tumor-cell death. The PARP inhibitor olaparib has been shown to have clinical efficacy in patients with a germline BRCA mutation and ovarian or breast cancer.”
The results of the Phase III randomized, double-blind study with a placebo control group show that, in essence, the drug treatment regimen stalls the progression of the disease. Of the 3,315 patients who underwent screening, 154 fit the study criteria to be assigned to trial intervention, thus 92 received the treatment and 62 received the placebo.
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“The median progression-free survival was significantly longer in the olaparib group than in the placebo group (7.4 months vs. 3.8 months),” Dr. Golan’s study details.
“I kind of always felt that this would be the results,” Dr. Golan explains in a video by Sheba Medical Center, “I’m in the trenches, I’m with the patients, so I was almost sure this was going to be a positive study just based on the observations I’ve made over the past decade… For the field, this is a huge thing. This is the first phase three biomarker-selected study to be positive in pancreatic cancer.”
Patients took two olaparib pills twice a day, and according to Hadas the treatment was “nothing compared to chemotherapy,” of which he is “still suffering from side effects.”
Scientists have likened using chemotherapy to treat metastatic pancreatic cancer to using a wrecking ball to open a door – yes, the door may eventually open, but there will be lots of other damage too. Hadas explains that “four years later” he still has numbness and pain in his legs and hands because of nerve damage resulting from chemotherapy.
“Talia was quite different from the first oncologist I met,” Hadas says, “The first thing I remember when we came into the room was that she had a big smile on her face, and maybe that seems not important, but for me it was quite different because it changed the whole approach and showed a positive attitude. She never promises things she can’t do, but she gives you hope, and that’s the main thing.”
Dr. Golan’s treatment represents a breakthrough for precision medicine in cancer research, working more like a lock and key to open this symbolic “door.” Hadas explains the drug has “minor side-effects,” such as fatigue, but claims to have a “very, very good quality of life” that allows him to do the things he loves, including spending time with his family, gardening, sculpting, and going on long walks.
Hadas has been on the treatment for four years and is now in full remission, he tells NoCamels. His wife Ilanit explains, “It’s unbelievable for him to have the opportunity to see our children grow up and have time with them, because that’s what we always talked about, was having time together, for us as a couple and as a family.”
Dr. Golan’s POLO trial not only represents the progression of cancer treatment towards precision medicine, but offers “hope” and “time” to those with the most advanced form of pancreatic cancer, underscoring the importance of participating in clinical trials.
“It was incredibly meaningful to be a part of this journey with my patients, for those that it helped and even for those that unfortunately, this strategy was not beneficial,” Dr. Golan explains in the interview, “I’m extremely grateful to the patients and their families for participating in this clinical trial.”