Chemotalk Newsletter

Chemotalk Newsletter, Vol. 111 July 1, 2017

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So...half the year is officially over, and so is the annual meeting of the American Society of Clinical Oncology (ASCO).  Many researchers deliver the results of their studies at this event, the premiere oncology gathering of the year.  From this year's conference, here's some news we can use...


By Leah Lawrence

    Patients with stage III COLON CANCER who maintained a healthy lifestyle during and after treatment had a 42% reduced risk for death and a trend for a lower chance of recurrence compared with patients with less healthy lifestyles, according to the results of a study (abstract 10006) presented during a press conference ahead of the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting.

    The definition of healthy lifestyle was based on guidelines called "Nutrition and Physical Activity Guidelines for Cancer Survivors" released by the American Cancer Society; the guidelines include recommendations for maintaining a healthy body weight; engaging in physical activity; and eating a diet high in whole grains, vegetables, and fruits, and low in red or processed meats, with only moderate alcohol intake.

    "Individuals often seek information on what they can do to lower risk of cancer recurrence, including changes to lifestyle," said Erin Van Blarigan, ScD, assistant professor of epidemiology and biostatistics at the University of California, San Francisco, during the press conference. "The American Cancer Society released guidelines based on scientific studies but it is not known if patients who followed these guidelines actually lived longer."

    The prospective study included 992 patients with stage III colon cancer enrolled in an adjuvant CHEMOTHERAPY trial from 1999 to 2001. Patients were enrolled within 8 weeks of surgery and received 6 months of adjuvant chemotherapy. The trial assessed lifestyle twice using validated surveys.
Patients were assigned a score from 0 to 6 (0 = no healthy behaviors) that measured the degree to which their lifestyle matched the American Cancer Society guidelines.

    With a median follow-up of 7 years, there were 335 cancer recurrences and 299 deaths. Compared with 26% of patients with the least healthy lifestyle (score 0­1), the 9% of patients with the healthiest lifestyle (score 5­6) had a 42% lower risk for death (hazard ratio [HR], 0.58; 95% CI, 0.34­0.99; P = .01 for trend). They also had a trend toward improved disease-free survival (HR, 0.69; 95% CI, 0.45­1.06; P = .03 for trend).

    Alcohol consumption is included in the guidelines for cancer prevention, but not cancer survivors. When alcohol was included in the lifestyle score, the adjusted HRs for patients with 6­8 points compared with 0­2 points were 0.49 for overall survival (P = .002 for trend), 0.58 for disease-free survival (P = .01 for trend), and 0.64 for recurrence-free survival (P = .05 for trend).

    Commenting on the results of the study, ASCO President Daniel F. Hayes, MD, said, "It should be emphasized that the authors are not suggesting that a healthy lifestyle alone should be considered a substitute for standard chemotherapy and other treatments for colon cancer, which have dramatically improved survival. Rather, patients with colon cancer should be optimistic, and they should eat a healthy diet and exercise regularly, which may not only keep them healthier, but may also further decrease the chances of the cancer coming back."

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By Dave Levitan

    Adding the novel CD20 inhibitor ublituximab to ibrutinib offered improved response rates and greater depth of response over ibrutinib alone in patients with RELAPSED/REFRACTORY CHRONIC LYMPHCYTIC LEUKEMIA (CLL), according to results of the phase III GENUINE trial (abstract 7504).

    "Ibrutinib has transformed the management for patients with relapsed CLL," said Jeff P. Sharman, MD, of the Willamette Valley Cancer Institute and Research Center in Eugene, Oregon. "Unfortunately for patients with high-risk molecular features, such as 11q deletion, 17p deletion, or TP53 mutation, relapses remain problematic, and improving clinical outcomes in this patient population remains an unmet medical need."

    In earlier studies, ublituximab showed single-agent activity in rituximab-refractory CLL patients, and a phase II trial in combination with ibrutinib showed an overall response rate of approximately 88%.

    Sharman presented results of the GENUINE trial at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. The open-label trial randomized 126 patients to either ublituximab plus ibrutinib (64 patients) or ibrutinib alone (62 patients); 9 patients never received treatment. The trial initially planned overall response rate (ORR) and progression-free survival (PFS) as co-primary endpoints, but due to enrollment problems the investigators reduced the target number of patients and changed PFS to a secondary endpoint.

    All patients had relapsed/refractory CLL, with confirmed presence of 17p deletion, 11q deletion, and/or TP53 mutation. Patients had a mean age of 67 years, and a mean time from diagnosis to randomization of approximately 6.5 years.

    The combination therapy patients had an ORR of 78%, compared with 45% with ibrutinib alone (P < .001). Furthermore, 19% of ublituximab patients were minimal residual disease (MRD)-negative, compared with 2% of ibrutinib monotherapy patients. In the combination group, 66% of patients had a more than 75% change in nodal size, compared with 52% of monotherapy patients.

    The hazard ratio for progression with ublituximab was 0.559 (95% CI, 0.216­1.443; P = .229), but again, the study¹s slow enrollment meant it was not adequately powered to assess PFS.

    The safety profile was generally similar to that seen with ibrutinib alone, with the exception of infusion reactions. More than half of the ublituximab patients (54%) experienced an infusion reaction of any grade, and 5% had a grade 3/4 infusion reaction; oral ibrutinib obviously resulted in no such reactions.

    "The GENUINE study met its primary endpoint, demonstrating that ublituximab in combination with ibrutinib yields superior ORR to ibrutinib alone, with greater number of responses and greater depth of response," Sharman concluded.

    Nitin Jain, MD, of MD Anderson Cancer Center in Houston, agreed that the addition of ublituximab may offer a promising option in relapsed/refractory patients. "Certainly a longer follow-up of this study would be required to see what happens to these patients over time," he said.

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    An experimental treatment for BLADDER CANCER  will move into an early phase clinical trial under an agreement signed between Cancer Research UK and Cancer Research Technology (CRT), the charity's commercial arm, and Canadian biotechnology company Sitka Biopharma Inc ., a spin-off of The Centre for Drug Research and Development (CDRD) and the University of British Columbia (UBC), financed by Quark Venture .

    The new treatment called STK-01 is being developed to improve delivery of chemotherapy for non-muscle invasive bladder cancer (NMIBC), in patients whose tumour has not yet penetrated into the muscle layer of the bladder wall.

    Standard treatment for NMIBC involves removal of the tumour followed by intravesical therapies (delivered by catheter directly into the bladder) to eliminate residual disease and prevent recurrence and progression. STK-01 uses a unique nanoparticle polymer technology to deliver the chemotherapy drug docetaxel.

    Docetaxel is an effective chemotherapy drug but it can be difficult to deliver enough of the drug to the bladder to treat the cancer. STK-01 may overcome this resulting in the tumour being exposed to much higher levels of the drug. In preclinical studies STK-01 has been shown to greatly enhance docetaxel penetration and retention in the bladder wall, and is extremely effective at eliminating tumours in mouse models.

    Under the agreement, Cancer Research UK and Sitka will share the cost of the development and production of STK-01 for the clinic.  Cancer Research UK's Centre for Drug Development (CDD) will then fund and manage a Phase I clinical trial of STK-01 in bladder cancer patients, to evaluate drug safety, toxicity, drug delivery and how it compares with giving docetaxel alone.

    The trial will take place across the Experimental Cancer Medicine Centres (ECMC) network, a nationwide initiative funded by Cancer Research UK and the UK's four Health Departments.  Dr Michael Parr, Sitka Biopharma's President and Chief Scientific Officer, said: "This agreement is very significant for Sitka as it will validate our preclinical therapy and take another step closer to providing an effective treatment for bladder cancer patients. Working with Cancer Research UK, CRT and CDD ­ world leaders in the development of cancer treatments ­ has helped us reach a significant value-creation point for Sitka, taking it from a pre-clinical to clinical stage company. Results of this work will be applied to new therapeutic technologies in development for other forms of cancer, such as ovarian cancer, and provide effective treatments for even more patients."

    Dr Nigel Blackburn, Cancer Research UK's director of drug development, said: "More than 5,000 people die from bladder cancer each year in the UK and we urgently need to find new and better ways to treat patients. We hope this experimental approach will improve survival for patients with invasive disease by increasing the amount of chemotherapy that can reach the tumour."Without our innovative CDP scheme it might have been years before this treatment reached patients so we're pleased to work with Sitka Biopharma to accelerate development of this promising technology."

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    It's just one step. Flushing the bladder with a common chemotherapy drug after a cancerous tumor is surgically removed reduces the chances of that cancer returning. Canadian and European clinical trials have proven this true and now a major U.S. study has done the same.

    Dr. Edward Messing, an investigator with SWOG, the international clinical trials network funded by the National Cancer Institute, has found that an immediate infusion of the common chemotherapy agent gemcitabine after the removal of a bladder cancer tumor will significantly reduce the risk of cancer recurrence. The Winfield W. Scott Professor and Chairman of Urology at the University of Rochester, Messing will present results of this Phase III, blinded clinical trial during a May 15 oral presentation at the annual meeting of the American Urological Association (AUA) held May 12-16 in Boston.

    "This one extra step, using a drug that's fairly inexpensive, has impressive results," Messing said. "Urologists in Europe and Canada have been doing this procedure for more than 20 years with other chemotherapy drugs, with the research to prove it. Even the AUA recommends it. Now that we've got results from an American study, using a readily available drug that is very well-tolerated, maybe American urologists will start using gemcitabine this way. I certainly hope this finally changes our standard of care."

    Messing is former president of the Society of Urologic Oncology and, in 2013, was awarded the prestigious Presidential Citation from the AUA for his work as a bladder cancer researcher and educator. Messing led a SWOG team that conducted the trial, S0337, which enrolled 406 eligible patients with non-muscle invading bladder cancer. Bladder cancer is the sixth most commonly diagnosed cancer in the United States, and the third most common among men. The low grade, non-muscle invasive form of the disease is common, making up about half of all newly diagnosed cases. Treatment includes a procedure called transurethral resection for bladder tumor, or TURBT, which involves a surgeon removing cancerous tissue from the bladder.

    In the Messing study, patients were randomized into two groups. One group, after TURBT, received a single 3.5-ounce instillation of gemcitabine, which was administered directly after surgery and allowed to sit in the bladder for one hour. The drug kills cancer cells, and is often used to treat advanced bladder cancer in combination with the chemotherapy drug cisplatin. The other group of patients, after TURBT, received an infusion of saline only. Both groups were followed for four years. Results were strong and clear: There was a significant 34 percent reduction in risk of recurrence for patients receiving the gemcitabine infusion. While more of those patients experienced moderate post-surgical pain, investigators found, they experienced no other additional side effects, such as bleeding, compared with the patients who received a saline infusion alone.

    "The big deal here is that cancer recurrence is common for people diagnosed with this less aggressive form of bladder cancer," Messing said.
"I know some patients who undergo four TURBT procedures a year. If we can cut down on these recurrences, we will save a lot of people a lot of pain, money, and time lost to recovery."

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See you next month...


And if you have any thoughts of how this newsletter could be improved, please email me directly, at

Elaine Jesmer

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