The OBR Blog

September 12, 2018 - 11:09 pm comments0 Comments

By Christina Bennett, MS

Tennessee Oncology, New York Cancer & Blood Specialists, and West Cancer Center have joined forces to form a new company, OneOncology. Backed by more than $200 million from investor General Atlantic, OneOncology officially launched on Tuesday, September 12, and will bring together more than 225 community oncologists from more than 60 national sites of care. The joint venture comes at a time when community oncologists are facing more challenges than ever to keep practice doors open and stay competitive in the current healthcare environment.

“The pace of innovation in drug therapy, in medical technology, and in practice approaches is very challenging for even the largest centers to keep up with,” said Tracy Bahl, President and Chief Executive Officer at OneOncology. Among the myriad of challenges are keeping up with the pace of regulation and the ability to access capital to advance and expand the continuum of cancer care.

The need to confront those challenges was, in part, a driver of the creation of OneOncology.

“Approximately 30 percent of community oncology practices in the country have gone out of business in the last five years due to the pressures faced,” said Jeffrey Patton, MD, President and CEO of Tennessee Oncology. Dr. Patton is also president of physician services at OneOncology. “We need a solution to help keep the choice and the option for community oncology to be viable in the market place,” he said.

Lee Schwartzberg, MD, a member of the OneOncology board of directors and executive director of West Cancer Center, said that the transition to value-based care requires a new infrastructure that even experienced practices need. “In order to make this change to value-based care, we need to partner, and we believe that OneOncology is a perfect vehicle to enhance this transformation,” he said.

Dr. Patton echoed a similar view, “Even at a practice with the size and scale of Tennessee Oncology, we’re convinced that to compete and survive in the value-based world, we need larger scale, more expertise, and better technologies to survive long-term as we move toward value-based care.”

Peter Ellis, MD, Deputy Director of Clinical Services and Associate Chief Medical Officer at UPMC Hillman Cancer Center, told OBR he is not surprised by the formation of OneOncology. In fact, he likened it to the formation of American Oncology Resources, Inc., (now U.S. Oncology) back in the 1990s.

It makes sense, Dr. Ellis said, given that oncology reimbursement continues to be challenging and Medicare and other payers are being aggressive in their reductions in reimbursement. “In order to stay efficient and be able to continue to provide the best quality care for patients, size and economics matter.” He added, “If [the three practices] didn’t bind together, they’d be vulnerable to the whims of reimbursement.”

Representatives from OneOncology assert that the company size will leverage greater purchasing power and help reduce costs. Access to capital will help practices expand to meet the needs of their communities. The rural cancer care setting is one example of how OneOncology may improve the delivery of care. In rural settings, meaningful services are not necessarily provided in the community, resulting in patients travelling long distances for radiation or chemotherapy, which is not only an inconvenience but also impacts adherence, and in turn, survival rates.

Bahl explained that before, a practice might have had to dip into its own pockets or find some other source of capital, and now with OneOncology, “we can identify and address that need, with the capital that OneOncology has available.”

OneOncology will also offer expertise for providers. “We’ll build a broader team with each one of our [founding] partners,” said Robin Shah, Chief Development and Marketing Officer at OneOncology. Providers will also have access to experts in technology, finance, operations, managed care, and all the other services that surround the ability to operate an oncology practice.

Dr. Patton explained that the advantage of having a network of practices across the country is access to best practices, and by having a common IT platform (provided by Flatiron), providers will be able to share and implement those best practices.

In the long-term, the vision of OneOncology is to “partner progressively” with other leading community oncology practices across the country.

June 05, 2018 - 09:06 pm Posted in ASCO Conference Coverage comments0 Comments

By Lynne Lederman, PhD

On this final day of the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting we look at two late breaking presentations. LBA 4008, presented late yesterday, showed proton pump inhibitors with low dose aspirin for at least 7 years offers modest benefits for people with Barrett’s esophagus, a risk factor for the development of adenocarcinoma of the esophagus. And, LBA 3505, presented today showed no benefit for using hyperthermic intraperitoneal chemotherapy (HIPEC) during surgery to treat most patients with colorectal cancer with colorectal peritoneal carcinomatosis, suggesting that those patients with CRC that has spread only to the peritoneum can avoid HIPEC treatment.

Chemoprevention of esophageal cancer with esomeprazole and aspirin therapy: efficacy and safety in the phase 3 randomized factorial ASPECT trial (LBA4008)

Janusz Jankowski, MD, Royal College of Surgeons, Ireland, presented an updated analysis of the ASPECT trial. The analysis showed that the risk of developing precancerous, high grade dysplasia or esophageal cancer could be reduced, and that the risk of death from any cause was delayed in individuals with Barrett’s esophagus (BE) with the use of the proton pump inhibitor (PPI) and low dose aspirin. This 7-year study is important because esophageal cancer, which is associated with BE is difficult to screen and treat, and the drugs used in the study, esomeprazole (a PPI) and aspirin, are dosed orally and available over the counter. Dr. Jankowski cautioned that people with heartburn should discuss their risk of BE with their health care provider and should not self-medicate with the study drugs.

Esophageal adenocarcinoma has a 5-year survival rate of less than 10%, and is increasing in incidence, probably due to an increase in gastro-esophageal reflux and BE, which are both associated with inflammation. PPIs reduce acid reflux, and aspirin reduces inflammation, so both agents can be preventative.

This study enrolled 2,563 patients with ≥1 cm BE and no high grade dysplasia or esophageal adenocarcinoma at baseline. Patients were randomly assigned 1:1:1:1 in a 2 x 2 factorial design to high or low dose esomeprazole alone or in combination with low dose aspirin. The primary composite endpoint was time to all-cause mortality, esophageal adenocarcinoma, or high grade dysplasia.

Median follow-up was 8.9 years. High dose esomeprazole had a statistically significant benefit on the combined endpoint compared with standard dose esomeprazole (P=.0459). Aspirin had no benefit in the no-aspirin arm in the primary analysis. Dr. Jankowski said it was stunning that the serious adverse event rate was low, about 1%.

In discussing this trial, Zev Wainberg, MD, David Geffen School of Medicine, UCLA, pointed out that despite the absolute benefits of high dose PPI and use of aspirin, there are many unanswered questions. Until there are more data, the question of whether all patients with BE should receive treatment with high dose PPI plus low dose aspirin can’t be answered.

A UNICANCER phase III trial of hyperthermic intra-peritoneal chemotherapy (HIPEC) for colorectal peritoneal carcinomatosis (PC): PRODIGE 7 (LBA3505)

This randomized, phase 3 trial (NCT00769405) showed that individuals with advanced colorectal cancer (CRC) may not require treatment with hyperthermic (heated) intraperitoneal chemotherapy (HIPEC) during surgery. HIPEC does not offer a survival advantage compared with surgery alone. The study results were presented by François Quenet, MD, Institut Régional du Cancer de Montpellier, Montpellier, France.

Patients with peritoneal CRC metastases are known to have a significantly worse prognosis than those with no peritoneal metastases.

Prodige 7 was a phase 3 trial in patients with peritoneal carcinomatosis of CRC origin who underwent complete surgical resection to ≤1 mm, then were randomly assigned to HIPEC (n=133) or no HIPEC (n=132), followed by systemic chemotherapy per physician choice for 6 months which could be administered pre-operatively, post-operatively, or both. Patients who had a peritoneal cancer index (PCI) of <25 were eligible for enrollment. PCI is prognostic for survival. Patents in the study had a median PCI of 10.

At a median follow-up of 64 months, the median overall survival (OS) was not statistically significantly different between groups at 41.2 months in the non-HIPEC group and 41.7 months in the HIPEC group. Median recurrence-free survival was also similar between the two groups at 11.1 months in the non-HIPEC group and 13.1 months in the HIPEC group. In a subgroup analysis, as expected, patients with lower PCI scores had longer OS. For patients with a PCI score of 11 to 15, there was a significant survival advantage for patients who received HIPEC versus none. However, there were only 18 (13.5%) such patients in the HIPEC group and 28 (21.2%) in the non-HIPEC group.

The overall mortality rate at 30 days after surgery was 1.5% in both groups, and adverse events were comparable between groups at this time point. At 60 days, the total mortality rate was 2.6%. At 60 days, the  rate of adverse events in the HIPEC group was significantly higher than that in the non-HIPEC group (24.1% versus 13.6%; P=.03). Hospital stays for the HIPEC group were also significantly longer.

Dr. Jankowski concluded that more research is needed to determine if there are patients with CRC metastases confined to the peritoneum who would still benefit from receiving HIPEC with surgery. Patients with a low PCI are not likely to benefit from HIPEC. The curative management of peritoneal carcinomatosis by cytoreductive surgery in this study yielded unexpectedly good OS results.

People with CRC metastases confined to the peritoneum with a low peritoneal cancer index can likely forgo HIPEC, whereas those with a high index may not benefit from either surgery or HIPEC. Meanwhile, other types of chemotherapy may be more effective than oxaliplatin, the type of chemotherapy used in HIPEC for this study.

In discussing this study, Larissa Temple MD Rochester Medical Center, said that it is too early to tell if this study will be practice changing, in part because of the relatively low median PCI score. A very high resection rate in this study likely contributed to a 30 and 60 day mortality lower than in retrospective data. Other ongoing randomized, controlled trials should provide more information as role of HIPEC treatment for CRC metastases confined to the peritoneum evolves.

June 04, 2018 - 09:06 pm Posted in ASCO Conference Coverage comments0 Comments

by Lynne Lederman, PhD

Several late-breaking abstracts were presented today at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting. These studies include LBA1509, identifying new tumor types with high microsatellite instability are associated Lynch syndrome; LBA2553, a retrospective study showing the effect of a precision medicine approach on survival across tumor types; LBA4001, describing a chemotherapy regimen that prolongs survival in pancreatic cancer, and LBA4002, demonstrating that preoperative chemotherapy with radiation also increases survival in pancreatic cancer.

Pan-Cancer Microsatellite Instability Predicts for the Presence of Lynch Syndrome (LBA1509)

Results of a prospective genomic study of 15,045 tumor samples from over 50 types of cancer reported by Zsofia K. Stadler, MD, Memorial Sloan Kettering Cancer Center, (MSKCC) showed that patients whose tumors have high microsatellite instability (MSI-H), a marker of a large number of genetic mutations resulting from an inability of cells to repair damaged DNA are also more likely to have Lynch syndrome, an inherited that increases the risk of multiple types of cancer.

Tumors from patients treated at MSKCC were analyzed with a genomic test, MSK-IMPACT, which uses next-generation sequencing (NGS) to detect mutations in cancer-related genes as well as MSI. Blood samples were also tested for germline mutations (deficiency) in DNA mismatch repair genes (MMR-D).

Genomic analysis were used to classify tumors into 3 groups: MSI-stable (MSS, no MSI; 93.2% of tumors), MSI-intermediate (MSI-I, moderate levels of MSI; 4.6%)), and MSI-H (2.2%). Inherited mutations in Lynch-syndrome associated genes occurred in 16% of those with MSI-H versus 1.9% of those with MSI-I and 0.3% of those with MSS tumors. Nearly half of patients had cancer types not or rarely associated with Lynch syndrome, including mesothelioma, sarcoma, and adrenocortical cancer, and 45% did not meet Lynch syndrome genetic testing criteria. MMR-D was found in 98.3% of the 57 MSI-I/MSI-H tumor samples tested.

Dr. Stadler said that findings suggest that all patients with MSI -H or MMR-D tumors should be tested for Lynch syndrome whatever the cancer type or personal or family history of cancer.

Precision Medicine: Clinical Outcomes Including Long-Term Survival According to the Pathway Targeted and Treatment Period: The IMPACT Study (LBA2553)

Apostolia M. Tsimberidou, MD, PhD, MD Anderson Cancer Center, Houston, presented the results of a study to assess the impact of precision medicine approaches on the survival of patients with multiple types of cancers. She said that the findings from the Initiative for Molecular Profiling in Advanced Cancer Therapy (IMPACT) study (NCT00851032) demonstrate that NGS of tumors can be used to optimize therapy and should be used to help select treatment in difficult-to-treat cancers.

The IMPACT study enrolled patients who had received all possible standard treatment options or who had incurable, rare cancers. Tumors were tested using CLIA-certified molecular testing. Treatment was matched targeted therapy if available, otherwise therapy was non-matched. Cancers included GI, gynecologic, breast, melanoma, and lung. Of 3,743 patient tumors tested, 1,307 (34.9%) had one or more targetable molecular alteration; 711 of these patients (54.4%) were assigned to matched targeted therapy and 596 (45.6%) were assigned to non-matched therapy.

For evaluable patients, the 3-year overall survival (OS) rate was 15% in patients receiving matched targeted therapy (n =697) versus 7% in the non-matched group (n=571) (HR, 0.67; P<.001). The 10-year OS rates were 6% versus 1%, respectively, with a plateau of OS in the matched group beginning at 3.2 years.

Matched therapy was an independent factor predicting longer survival in a multivariate analysis. PI3K/AKT/mTOR pathway abnormalities were associated with poorer outcomes compared with other genetic alterations. Ongoing clinical trials to further precision medicine approaches to treatment include the IMPACT2 and ASCO’s TAPUR trials.

Unicancer GI PRODIGE 24/CCG PA.6 trial: a multicenter international randomized phase III trial of adjuvant mFOLFIRINOX versus gemcitabine (gem) in patients with resected pancreatic ductal adenocarcinomas (LBA4001)

Thierry Conroy, MD, Institut de Cancerologie de Lorraine, Nancy, said the PRODIGE 24/CCG PA.6 trial showed that adjuvant mFOLFIRINOX therapy is superior to gemcitabine, the standard of care for the past 10 years.

Patients with non-metastatic pancreatic ductal adenocarcinoma who had all visible tumor surgically removed were randomly assigned to gemcitabine (n=246) or mFOLFIRINOX (n=247) for 6 months. At a median follow-up of 33.6 months the disease-free survival (DFS), the primary endpoint, was 21.6 months in the mFOLFIRINOX groups versus 12.8 months in the gemcitabine group (HR 0.58; 95% CI 0.46, 0.73; P<.0001). The median OS was 54.4 months for mFOLFIRINOX versus 35.0 months for gemcitabine (HR 0.64; 95% CI 0.48, 0.86; P=.003).

Although there were more severe adverse events (AEs), primarily hematologic, with mFORFIRINOX (76% versus 53%), they were manageable. It is recommended that patients be screened for underlying heart disease before treatment as a history of ischemic heart disease is a risk with either treatment, especially mFOLFIRINOX.

Dr. Conroy suggested mFOLFIRINOX should be considered a new standard of care for pancreatic cancer after surgical resection. Ongoing trials are examining optimal timing of chemotherapy in this setting, including pre-surgery as neoadjuvant therapy and dosing of half the cycles before and half after surgery as perioperative chemotherapy.

Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC-1): a randomized, controlled, multicenter phase III trial (LBA4002).

In other encouraging news for patients with pancreatic cancer, the result s of the PREOPANC-1 trial showed that patients (n=119) randomly assigned to chemoradiotherapy for 10 weeks prior to surgery for pancreatic cancer as well as post-surgical chemotherapy had a better DFS than patients (n=127) who were randomly assigned to the same amount of chemotherapy after immediate surgery (9.9 months versus 7.9 months; P=.023). The 2-year survival for the preoperative chemotherapy group was 42% versus 30% in the post-surgery chemotherapy group. There was no significant difference between groups in median OS; however, in the subgroups of patients with complete resections, median OS was 42.1 months for preoperative chemotherapy versus 16.8 months for immediate surgery. Distant metastases-free interval was longer for the presurgical treatment group (HR 0.71; P=.013), as was locoregional recurrence-free interval (HR 0.55; P=.002).

Although these results are preliminary, Geertjan Van Tienhoven, MD, PhD, said the study investigators believe that this trial may be practice-changing. After the final analysis, efforts will be made to test for more effective preoperative treatments, eg, FOLFIRINOX alone or combined with stereotactic radiation therapy.

June 03, 2018 - 10:06 pm Posted in ASCO Conference Coverage comments0 Comments

By Christina Bennett, MS

In addition to today’s exciting plenary sessions at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, several high-impact clinical trial results were reported.

KEYNOTE-407: Practice Changing (Abstract 105)

An interim analysis of the phase III KEYNOTE-407 trial showed a more than four-month longer median overall survival (OS) for metastatic squamous non–small-cell lung cancer (NSCLC) patients who received pembrolizumab plus traditional chemotherapy compared with those who received placebo plus chemotherapy.

“Squamous non–small cell lung cancer has been an orphan, almost step child, in the development of chemo[immunotherapy] for metastatic lung cancer,” said Charu Aggarwal, MD, MPH, Assistant Professor of Medicine at The Hospital of The University of Pennsylvania. “This is the first time that we are actually seeing upfront use of immunotherapy in combination with chemotherapy for squamous lung cancer.”

For KEYNOTE-407, a total of 559 participants with untreated metastatic squamous NSCLC were enrolled and randomized to receive either pembrolizumab plus chemotherapy or placebo plus chemotherapy. At the time of interim analysis, 204 participants have been randomized, 101 to the pembrolizumab plus chemotherapy arm and 103 to the placebo plus chemotherapy arm. Participants were stratified by PDL1 status.

Median OS was 15.9 months for the pembrolizumab plus chemotherapy arm and 11.3 months in the placebo plus chemotherapy arm. The median progression-free survival (PFS) was 6.4 months for pembrolizumab plus chemotherapy arm compared with 4.8 months for the placebo plus chemotherapy alone arm.

These data suggest that pembrolizumab plus chemotherapy should become a new standard of care for the first-line treatment of metastatic squamous NSCLC across all the different levels of PDL1 expression, said study investigator, Luis Paz-Ares, MD, PhD, professor of medicine at the Hospital Universitario 12 de Octubre.

“Not only was there a PFS benefit, but there was a significant overall survival benefit with a hazard ratio of .6. There is no doubt in my mind that this benefits patients and that we need to adopt this starting today, if available,” said Dr. Aggarwal.

About the safety profile, Dr. Aggarwal said, “Overall, the toxicity profile seemed very manageable, and now we are very adept at managing immune-related toxicities since we’re been using these agents in the clinic.”

KEYNOTE-427: Frontline Pembrolizumab Monotherapy Gains Traction (Abstract 4500)

Interim results from the phase II KEYNOTE-427 trial showed a 38% response rate for advanced cleared cell renal cell carcinoma (RCC) patients receiving pembrolizumab monotherapy in the front-line setting. Three patients achieved a complete response, and 39 a partial response. The median progression-free survival was 8.7 months, and median overall survival has not been reached.

KEYNOTE-427, a single-arm, open-label design, enrolled participants with advanced clear cell or nonclear cell RCC. Eligible patients had measurable disease per RECIST criteria 1.1, no prior systemic therapy, and a Karnofsky performance status of greater than or equal to 70%. Participants received pembrolizumab at a dose of 200 mg IV every three weeks. Only data from Cohort A, which had 110 participants, were presented.

“The frequency of adverse events of special interest is consistent with what has been seen with pembrolizumab monotherapy in other tumor types,” said lead investigator David F. McDermott, MD, director of Biologic Therapy and Cutaneous Oncology Programs at Beth Israel Deaconess Medical Center.

“Treatment-related adverse events of any grade occurred in 80% of patients. Treatment-related grade 3 and 4 adverse events occurred in 30% of patients. Discontinuation due to treatment-related adverse events was reported in 11% of patients,” he said. “One patient died from treatment-related pneumonitis.”

Naomi Haas, MD, Associate Professor of Medicine at the Hospital of the University of Pennsylvania, described KEYNOTE-427 as a “really important” study.

Ipilimumab and nivolumab combination was FDA approved recently for first-line treatment in kidney cancer. “There’s a high response rate in that combination, but there’s also a lot of toxicity, and single agent pembrolizumab had an impressive response rate and less toxicity.”

She continued, “The complete response rate was not as high with the single agent pembrolizumab as it was in the ipilimumab and nivolumab combination, but it’s not clear to me that you can’t rescue some of those people later by adding a second agent and perhaps sparing people the toxicity, so I think it’s a really important first step to answering that, and I’d like to see something in the future that would include a single agent immune checkpoint inhibitor as a comparator arm in some of these combination immune checkpoint inhibitor trials.”

Erdafitinib, New Hope for Advanced Urothelial Cancer (Abstract 4503)

In the phase II study BLC2001, participants with metastatic or unresectable urothelial carcinoma who were treated with erdafitinib, an oral pan-fibroblast growth factor receptor (FGFR) inhibitor, had a 40% response rate. Three percent of patients had a complete response and 37% a partial response. These results come just a few months after the FDA granted Breakthrough Therapy Designation to erdafitinib for patients with metastatic urothelial cancer.

“This is really a very exciting trial,” commented Dr. Haas. “As in some of the other solid tumors, I think there’s a growing awareness that there are different subsets of urothelial cancer that might benefit from immune checkpoint inhibitors, and others that might benefit from other alternative treatment pathways.”

The trial enrolled advanced urothelial carcinoma patients with FGFR alterations, and 99 were treated with a median of 5 cycles of erdafitinib. Participants with prior treatment with immune check point inhibitors were eligible.

“This clinical trial with erdafitinib has met its primary objective, achieving an objective response rate of 40 percent,” said study presenter Arlene Siefker-Radtke, MD, Professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center.The median PFS was 5.5 months, and the median OS at the average follow-up of 9 months was 13.8 months. Ten percent of participants discontinued treatment as a result of side effects, and 7% had serious treatment-related adverse events.

“This [trial] had a very impressive response rate in people that were pretty heavily pre-treated, and it was interesting that some of the patients who responded to this drug were resistant to immune checkpoint inhibitors,” said Dr. Haas.

Another CAR-T Drives Forward (Abstract 7505)

The investigational CAR-T product lisocabtagene maraleucel for relapse/refractory non-Hodgkin lymphoma (NHL) showed durable responses, according to results from the phase I TRANSCEND NHL 001 trial. Lisocabtagene maraleucel is an anti-CD19 CAR T-cell.

The overall response rate for patients in the CORE data set (which were patients who met all study inclusion criteria) was 49% and 46% complete response at 6 months. In the trial, lisocabtagene maraleucel was evaluated at two dosing schedules (single dose vs two-dose), and across both dosing levels 93% of patients who achieved the 6-month timepoint remained in remission at last follow-up.

“This anti-CD19 CAR T-cell has remarkable efficacy in a group of highly refractory aggressive B-cell non-Hodgkin lymphoma patients,” said Caron Jacobson, MD, who discussed the study. Dr. Jacobson is Medical Director of the Immune Effector Cell Therapy Program at Dana-Farber Cancer Institute.

“The median overall survival has not been reached in this population,” noted Jeremy Abramson, MD, Clinical Director, Center for Lymphoma at Massachusetts General Hospital. Nearly 90% of patients who achieved a complete response remain alive at 1 year. “These [outcomes] are far superior of what we would have anticipated with conventional therapies in largely chemo-refractory DLBCL population.”

About toxicity, Dr. Abramson said, “I think strikingly, lisocabtagene maraleucel has shown a low and manageable toxicity profile, with very low rates of severe CRS [cytokine release syndrome] and neurotoxicity, at 1 percent and 13 percent respectively. We continue to therefore evaluate this product for an outpatient administration.”

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