LSU Stanley S. Scott Cancer Center

 OncLive® welcomed the Stanley S. Scott Cancer Center into its Strategic Alliance Partnership program today as the two organizations announced they would band together to share news about the Center’s advances in the fight against cancer. The Center is part of the new Louisiana State University’s Health Sciences Center recently built in downtown New Orleans.

With the new partnership, OncLive’s editorial and marketing groups will bring visibility to the LSU Stanley S. Scott Cancer Center as it works to lessen the burden that cancer imposes on its community, via research, clinical trials and studies of minority health and health disparities.

The Center’s initiatives include a minority-based clinical oncology program that helps members of the community participate in National Cancer Institute clinical trials. One of 13 such programs funded by the NCI, this initiative serves southern Louisiana and Mississippi. The Cancer Center has also united efforts with the first National Institutes of Health-funded Health Disparities Research Center in Louisiana, with the goal of helping underserved populations in New Orleans.

“We can’t wait to inform others about the important community-focused work being done by the LSU Stanley S. Scott Cancer Center,” said Mike Hennessy Jr., president of Intellisphere Oncology and Healthcare Specialty Group. “It’s essential, in waging the fight against cancer, to focus on what’s going on at the community level, and that’s exactly what the Center does.” Intellisphere, LLC, a leading provider of healthcare publishing, research and education, is a part of the Plainsboro, N.J.-based Michael J. Hennessy Associates, Inc., family of businesses, of which OncLive is a part.

In partnership with Apogee Biotechnology Corporation, LSU Stanley S. Scott Cancer Center was recently awarded a $1.5 million contract by the National Cancer Institute to conduct clinical trials on the most common subtype of non-Hodgkin’s lymphoma.

“Our focus is on the people from the communities we serve,” said Augusto Ochoa, M.D., director of the Center. “Our new partnership with OncLive will make it easier for us to let those people know we are here for them.”

The LSU Stanley S. Scott Cancer Center joins more than 50 other leading cancer centers, nursing schools and physician groups around the country in partnering with OncLive.

“The Strategic Alliance Partnership program serves everyone committed to fighting cancer. When we work together and share our knowledge broadly, we are better armed to improve our efforts to overcome this devastating disease,” Hennessy said.

OncLive.comâ€¯is the official website for Intellisphere’s Oncology Specialty Group, which publishesâ€¯Oncology & Biotech News, OncologyLive, Oncology Nursing News, Contemporary Oncology and Contemporary Radiation Oncology.â€¯OncLiveâ€¯offersâ€¯oncology professionals resources and informationâ€¯they need to provide the best care forâ€¯theirâ€¯patients.â€¯Intellisphere, LLC, a leading provider of healthcare publishing, research and education,â€¯is partâ€¯ofâ€¯the Michael J. Hennessy Associates, Inc., family of businesses,â€¯based in Plainsboro, N.J.â€¯

MJH is also the parent company of CURE Media Group, which includes CURE® magazine, the largest consumer publication in the U.S. focused entirely on cancer, and curetoday.com, the magazine’s online resource. CURE reaches patients, cancer centers and advocacy groups, and combines science and humanity to make cancer understandable. For more information, visit https://www.onclive.com/, http://www.curetoday.com or http://www.mjhassoc.com/.

About the LSU Stanley S. Scott Cancer Center

The LSU Stanley S. Scott Cancer Center includes more than 100 researchers and physicians focused on helping members of their community reduce their chances of getting cancer, detecting cancer early and conducting new research into the disease. Its innovative programs include a mentoring initiative for junior investigators researching the immunobiology of cancer and other chronic diseases. In addition to conducting research, its health disparities research center also helps minority faculty become successful investigators, and trains minority nursing students in clinical research. For more information, please visit www.medschool.lsuhsc.edu/cancer_center.

For the LSU Stanley S. Scott Cancer Center: Richard Granen, 504-210-2971, rgran1@lsuhsc.edu

For OncLive: Becky Taylor, 609-240-6886, becky@btaylorpa.com

Articles

Strategic Alliance Partnership will strengthen outreach to cancer patients.

OncLive Teams Up With LSU's Stanley S. Scott Cancer Center to Publicize Center's Innovative Cancer Research and Community-Based Programs

The evaluation of noncytotoxic agents for the treatment of epithelial ovarian cancer has produced encouraging findings in recent months. This has led to the approval of new agents with novel mechanisms of action and continuing studies into many more potential therapies.

These are welcome developments for the treatment of patients with this malignancy. This includes approximately 22,000 women who are diagnosed annually with ovarian cancer in the United States alone.

Although epithelial ovarian cancer is a highly chemoresponsive tumor initially, the development of resistance is a common event. In fact, the majority of women with stage III-IV ovarian cancer, the most common stage at presentation, will relapse and eventually succumb to their disease.

This review will focus on recent clinically relevant findings of noncytotoxic agents for the treatment of ovarian cancer, including an expanded indication for bevacizumab (Avastin) and a new drug approval for olaparib (Lynparza).

The initial management of ovarian cancer typically includes a staging and debulking surgical intervention and a platinum plus taxane—based chemotherapy regimen. At the completion of this therapy, most patients will have no evidence of disease. However, up to 75% of women with advanced disease will relapse at a median time of approximately 10 months.

After recurrence, the duration of the platinum- free interval remains as the most important prognostic factor.

 Patients who relapse within 6 months of completing a platinum- based regimen are classified as platinum resistant, while those who relapse more than 6 months after treatment are classified as platinum sensitive.

Standard cytotoxic treatment for the latter group of patients includes a platinum-based regimen most frequently combined with paclitaxel,

However, the duration of response to each subsequent platinum-based regimen tends to become progressively shorter and eventually patients become platinum resistant.

Many cytotoxic agents have been evaluated in phase II clinical trials in the platinum-resistant setting. Response rates are typically 20% or lower and durations of response are short. Docetaxel,

 are probably the most active and best-studied agents.

Only a few of these agents have been evaluated in phase III randomized trials.

 It can be concluded from these studies that topotecan, paclitaxel, weekly paclitaxel, pegylated liposomal doxorubicin, and gemcitabine have comparable activity.

Many other agents were studied before the use of modern chemotherapy regimens and, therefore, their true activity in today’s environment is unknown.

Recently, etirinotecan pegol, an investigational topoisomerase I inhibitor, was reported to have encouraging activity in patients with heavily pretreated chemotherapy-resistant ovarian cancer.

 However, no further studies have been reported.

Several investigational cytotoxic agents were reported to have encouraging activity in phase II trials. However, phase III trials failed to demonstrate superiority over conventional agents.

 Indeed, no cytotoxic chemotherapy agent has been approved for the treatment of recurrent ovarian cancer since 2006.

Nearly 20 years ago, it was reported that VEGF was overexpressed in human ovarian tumors and that it conferred a poor prognosis.

 Similarly, it was observed that VEGF was directly associated with the development of ascites and carcinomatosis in animal models and that antibodies against VEGF inhibited tumor growth and ascites formation.

 These and other findings prompted researchers to evaluate the potential role of angiogenesis inhibitors in clinical trials in ovarian cancer.

Bevacizumab is, by far, the most extensively studied agent in ovarian cancer. Single-arm phase II studies have demonstrated significant activity of bevacizumab as a single agent

 or in combination with low-dose metronomic chemotherapy.

Despite the limitation of cross-comparison studies, the addition of low-dose oral cyclophosphamide appears to confer increased activity, as manifested by an impressive 6-month progression- free survival (PFS) with no significant increase in toxicity or cost. Several tyrosine kinase inhibitors have also been reported to have activity in recurrent ovarian cancer. However, they do not appear to have significant advantages over bevacizumab.

Based on these results, several inhibitors of angiogenesis were evaluated in phase III randomized trials in combination with chemotherapy. Studies have been conducted in combination with chemotherapy in frontline therapy for the treatment of patients with platinum-sensitive and platinum-resistant disease, as well as in maintenance treatment.

These studies have universally shown that the addition of bevacizumab to conventional chemotherapy improves response rate and PFS. However, improvements in overall survival have generally not been observed.

In November 2014, the FDA approved the use of bevacizumab in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan for patients with platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.

The approval was based on an international two-arm trial that compared bevacizumab plus chemotherapy of physician’s choice versus chemotherapy alone. The trial included 361 patients with platinum-resistant disease that had progressed less than 6 months after the most recent therapy. The participants had received ≤2 prior chemotherapy regimens.

Overall, the bevacizumab-containing regimens registered an improvement in median PFS of 6.8 months compared with 3.4 months for chemotherapy alone (HR, 0.38; 

 Patients who received bevacizumab plus paclitaxel demonstrated the largest improvement, with a median PFS of 9.6 months versus 3.9 months for chemotherapy alone (HR, 0.47).

Although there was no statistically significant improvement in overall survival for the bevacizumab- containing arms, the findings suggested that patients who have received paclitaxel in an earlier round of therapy may benefit from bevacizumab plus weekly paclitaxel.

The angiopoietin (Ang)—Tie axis is composed of two cytokines, Ang 1 and Ang 2, which regulate angiogenic pathways in late stages of neovascularization. These interact with the Tie2 receptor to mediate vascular remodeling. Ang 1 predominantly stabilizes endothelial junctions and increases pericyte coverage while Ang2 promotes endothelial sprouting and increases blood vessel density.

Trebananib (AMG 386) is an investigational recombinant peptide-Fc fusion protein that binds and neutralizes Ang 1 and Ang 2.

 Responses were observed in patients with ovarian cancer in a phase I study.

 A dose-dependent prolongation in PFS was observed when combined with paclitaxel in a randomized phase II study.

However, only modest activity was observed when trebananib was evaluated as a single agent.

 Overall, the agent is well tolerated, with fluid retention as its most common dose-limiting toxicity. These findings led to the development of randomized phase III trials for trebananib as frontline therapy and in the setting of platinumsensitive and -resistant disease.

Patients with recurrent ovarian cancer and a platinum-free interval of less than 12 months were enrolled in a phase III trial using the addition of trebananib to weekly paclitaxel. This treatment resulted in a significant improvement in response rate and PFS (primary endpoint). Although no differences were observed in overall survival, a subset analysis suggested a benefit in those patients with ascites present at baseline. 54,55 Results from additional phase III trials are expected.

Poly (ADP-ribose) polymerase (PARP) is an enzyme involved in base excision repair, a key mechanism in the repair of DNA single-strand breaks.56 

-deficient cells appear to be particularly susceptible to the effects of these drugs.

Olaparib is the PARP inhibitor that has been Strategic Alliance Partnership Program studied most extensively.

 It inhibits several isoforms of PARP. Olaparib inhibits tumor growth of various cell lines and decreases tumor growth in xenograft models. Increased efficacy was documented in 

Several clinical trials of PARP inhibitors, predominantly evaluating patients with 

 germline mutations, have been reported.59-63 Significant activity was reported in all of these studies, including early phase I trials.

In December 2014, the FDA approved olaparib for the treatment of recurrent ovarian cancer. This was approved for use in patients with a deleterious or suspected deleterious germline 

 mutation who have been previously treated with three or more prior lines of therapy. This approval was based on an international, multicenter, single-arm trial that enrolled 298 patients with a deleterious or suspected deleterious 

 mutation. This included 193 women with ovarian cancer, 137 of whom had measurable disease.

Olaparib was administered at a dose of 400 mg orally until disease progression or toxicity. The median number of prior chemotherapy regimens was five. The overall response rate was 34%, with a median duration of response of 7.9 months and a median PFS of 7 months.

The most commonly observed adverse events were fatigue (66%), nausea (64%), vomiting (43%), diarrhea (31%), and anemia (34%). However, toxicities of grade 3-4 severity were uncommon and were observed for the most frequently observed adverse events in 8%, 3%, 4%, 1%, and 18% of patients, respectively.

The activity of olaparib according to platinum resistance has only been evaluated in one small study that enrolled 37 women. A response rate of 46% was observed among 13 women with platinum-sensitive disease while the response among 24 women with platinum-resistant ovarian cancer was 33%.

Another small study included women with and without a 

 mutation. The response rates were 41% and 24%, respectively.

The efficacy of veliparib was reported in a phase II trial of 50 women with a known 

 Patients had received up to three prior chemotherapy regimens. Veliparib was administered orally at a dose of 400 mg twice a day. The overall response rate was 26%. The response among 20 patients with platinum-sensitive disease was 35%, while among 30 women with resistant disease, the response was 20%. Overall PFS was 8.1 months.

Rucaparib was evaluated among 35 women with a germline 

 mutation and platinum sensitive ovarian cancer.

 The number of prior chemotherapy regimens was two. Overall response rate was 66%.

As a group, these studies show that PARP inhibitors have significant activity in recurrent ovarian cancer. Activity is well documented in patients with a 

 germline mutation, and early findings suggest that this activity persists in high-grade serous ovarian tumors. Preliminary studies suggest a role when used as maintenance therapy, and confirmatory studies are ongoing.

			Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015 [published online January 5, 2015]. 

			Burger RA, Brady MF, Bookman MA, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. 

			Markman M, Hoskins W. Responses to salvage chemotherapy in ovarian cancer: a critical need for precise definitions of the treated population. 

			Eisenhauer EA, Vermorken JB, van Glabbeke M. Predictors of response to subsequent chemotherapy in platinum pretreated ovarian cancer: a multivariate analysis of 704 patients. 

			Parmar MK, Ledermann JA, Colombo N, et al. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. 

			Pujade-Lauraine E, Wagner U, Aavall-Lundqvist E, et al. Pegylated liposomal doxorubicin and carboplatin compared with paclitaxel and carboplatin for patients with platinum-sensitive ovarian cancer in late relapse [published online May 24, 2010]. 

			Pfisterer J, Plante M, Vergote I, et al. Gemcitabine plus carboplatin compared with carboplatin in patients with platinum-sensitive recurrent ovarian cancer: an intergroup trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG. 

			Rose PG, Blessing JA, Ball HG, et al. A phase II study of docetaxel in paclitaxel-resistant ovarian and peritoneal carcinoma: a Gynecologic Oncology Group study. 

			Markman M, Hall J, Spitz D, et al. Phase II trial of weekly single-agent paclitaxel in platinum/paclitaxel-refractory ovarian cancer. 

			Muggia FM, Hainsworth JD, Jeffers S, et al: Phase II study of liposomal doxorubicin in refractory ovarian cancer: antitumor activity and toxicity modification by liposomal encapsulation. 

			Bookman MA, Malmstrom H, Bolis G, et al: Topotecan for the treatment of advanced epithelial ovarian cancer: an open-label phase II study in patients treated after prior chemotherapy that contained cisplatin or carboplatin and paclitaxel.

			Shapiro JD, Millward MJ, Rischin D, et al: Activity of gemcitabine in patients wih advanced ovarian cancer: responses seen following platinum and paclitaxel. 

			Miller DS, Blessing JA, Krasner CN, et al. Phase II evaluation of pemetrexed in the treatment of recurrent or persistent platinum-resistant ovarian or primary peritoneal carcinoma: a study of the Gynecologic Oncology Group. 

			Coleman RL, Brady WE, McMeekin DS, et al. A phase II evaluation of nanoparticle, albumin-bound (nab) paclitaxel in the treatment of recurrent or persistent platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer: a Gynecologic Oncology Group study. 

			ten Bokkel Huinink W, Gore M, Carmichael J, et al: Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer.

			Rosenberg P, Andersson H, Boman K, et al. Randomized trial of single agent paclitaxel given weekly versus every three weeks and with peroral versus intravenous steroid premedication to patients with ovarian cancer previously treated with platinum. 

			Gordon AN, Fleagle JT, Guthrie D, et al. Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. 

			O’Byrne KJ, Bliss P, Graham JD, et al. A phase III study of Doxil/Caylex versus paclitaxel in platinum treated taxane naive relapsed ovarian cancer. 

			Mutch DG, Orlando M, Goss T, et al. Randomized phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer. 

			Ferrandina G, Ludovisi M, Lorusso D, et al. Phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in progressive or recurrent ovarian cancer. 

			Garcia AA. Salvage therapy for ovarian cancer. 

			Vergote IB, Garcia A, Micha J, et al. Randomized multicenter phase II trial comparing two schedules of etirinotecan pegol (NKTR-102) in women with recurrent platinum-resistant/refractory epithelial ovarian cancer.

			Kavanagh JJ, Gershenson DM, Choi H, et al. Multi-institutional phase 2 study of TLK286 (TELCYTA, a glutathione S-transferase P1-1 activated glutathione analog prodrug) in patients with platinum and paclitaxel refractory or resistant ovarian cancer. 

			Krasner CN, McMeekin DS, Chan S, et al. A phase II study of trabectedin single agent in patients with recurrent ovarian cancer previously treated with platinum-based regimens. 

The evaluation of noncytotoxic agents for
the treatment of epithelial ovarian cancer
has produced encouraging findings in
recent months, which has led to the approval of
new agents with novel mechanisms of action
and continuing studies into many more potential
therapies.

LSU Stanley S. Scott Cancer Center

OncLive Teams Up With LSU's Stanley S. Scott Cancer Center to Publicize Center's Innovative Cancer Research and Community-Based Programs

Novel Agents Signal Progress in the Management of Platinum-Resistant Ovarian Cancer