The annual meeting of the American Society of Clinical Oncology (ASCO) is just around the corner, and Kantar Health is excited to preview the top abstracts. The 2013 meeting promises to be packed with the latest data and trends from the world of oncology, but it may not have an overwhelming number of practice-changing, blockbuster presentations compared with conferences in the recent past. The following is a brief synopsis of the three abstracts that are likely to generate the most discussion and have the highest impact. For a full discussion of all 10 of our top abstracts, please see the associated article in the May issue of OBR Green.
Avastin in Newly Diagnosed Glioblastoma
Avastin® (bevacizumab, Roche/Genentech) was granted accelerated FDA approval in 2009 for the treatment of relapsed glioblastoma (GBM). In November 2012, results for the Phase III AVAglio trial showed that adding Avastin to chemoradiotherapy for the treatment of newly diagnosed GBM patients improved progression-free survival (PFS), but the interim overall survival (OS) results did not reach statistical significance. Presented at ASCO this year will be the results from the RTOG 0825 trial that has a nearly identical trial design as AVAglio. This plenary presentation could serve to provide a more convincing narrative for the use of Avastin in the newly diagnosed GBM setting.
Physicians are becoming familiar with Avastin showing a PFS benefit but not significantly affecting OS. This may give some physicians pause after the AVAglio results followed this same pattern. Will the RTOG 0825 trial change that perception, or will we see a similar pattern of PFS without OS? The availability and high use of Avastin in relapsed GBM may certainly confound the OS results from these studies, so it will be interesting to see whether there is any trend in the data. Given the high unmet need in GBM and the complete lack of active agents beyond temozolomide, the PFS benefit could be enough to maintain Avastin as a new option in newly diagnosed patients, but lacking OS could hinder its ability to become the new standard of care. Presentations: RTOG 0825, Abstract 1, Sunday, June 2, 1:50 PM; AVAglio, Abstract 2005, Saturday, June 1, 4:30 PM
FIRE-3: We’re “Burning” to Finally See a Head-to-Head of Avastin versus Erbitux in Colorectal Cancer
In KRAS wild type colorectal cancer (CRC), Avastin is currently the first-line standard of care in combination with chemotherapy in the United States, but European physicians are utilizing about equal amounts of Erbitux compared with Avastin, according to Kantar Health’s most recent CancerMPact® Treatment Architecture data. Both targeted agents significantly improve PFS compared with chemotherapy alone, and both have demonstrated a strong trend to OS benefit in recent studies. In the absence of comparative data between the two agents, the current practice has evolved based on safety profile, cost of therapy and order of market entry. In the United States, the Cancer and Leukemia Group B (CALGB) sponsored the Phase III 80405 study, and in Europe a German academic group initiated the FIRE-3 study, both comparing first-line chemotherapy in combination with Avastin or Erbitux in KRAS wild type patients. FIRE-3 will be the first to report at ASCO 2013.
Several aspects of the data will be key to evaluate. PFS and OS will take top billing, but other endpoints such as response rate, resectability of liver metastases, safety and its impact on dose intensity will also influence treatment patterns. European physicians are more likely to be influenced by the FIRE-3 results, given that the treatment arms closely resemble the treatment standards in Europe. The impact on the U.S. market may be lower, since U.S. physicians typically use FOLFOX in the first line in combination with Avastin, so they may not see the FIRE-3 study as accurately depicting their first-line treatment of choice, as chemotherapy is limited to FOLFIRI in that study. The FIRE-3 results could raise some serious questions if Erbitux can show superiority versus Avastin on any of the efficacy endpoints. Presentation: FIRE-3, Abstract LBA3506, Saturday, June 1, 4:45 PM
Stage I Results from CLL11: Obinutuzumab Plus Chlorambucil in Fludarabine-Ineligible Chronic Lymphocytic Leukemia
As a CD20 antibody, obinutuzumab (also known as GA101, Roche/Genentech) draws frequent comparisons to Rituxan® (rituximab, Roche/Genentech), but Roche hopes the unique epitope and glycosylation of obinutuzumab will sufficiently distinguish it from Rituxan and ultimately prove superior.
The presentation at ASCO 2013 will detail the efficacy results from the first stage of the Phase III CLL11 trial comparing obinutuzumab plus chlorambucil versus chlorambucil alone. In January 2013, Roche announced via press release that obinutuzumab plus chlorambucil significantly reduced the risk of disease worsening or death compared with chlorambucil alone, and the study met the planned requirements of the futility analysis allowing its continuation. Additionally in that release, the company stated their plans to file for regulatory approval based on the results of this phase of the study.
It is not entirely surprising that the combination of obinutuzumab plus chlorambucil showed superiority versus chlorambucil monotherapy, but it will be the results versus Rituxan plus chlorambucil that will really generate some buzz if obinutuzumab is able to out-duel Rituxan in terms of efficacy. The oncology community will likely have to wait another year for that data, but the ASCO presentation should give an idea of the magnitude of benefit achieved by adding obinutuzumab to chlorambucil, which could hint at probabilities for success in the second stage of the trial. Presentation: CLL11, Abstract 7004, Tuesday, June 4, 9:15 AM
In addition to the abstracts above, the full article discusses the key abstracts listed in the table below.
By Josh Garcia, Associate Consultant, Clinical & Scientific Assessment, Kantar Health
A sneak preview of four studies to be presented at the upcoming ASCO GI (American Society of Oncology Gastrointestinal cancer) meeting in San Francisco (January 20-22) shows that the era of personalized medicine has arrived. The studies, respectively, focused on intensity –modulated radiation therapy (IMRT) as a safer alternative to conventional radiotherapy for the treatment of anal cancer, sorafenib as a third-line treatment option for gastrointestinal stromal tumors (GIST) resistant to both imatinib and sunitinib, a new gene signature test to identify patients with colorectal cancer at high risk for recurrence, and early use of positron-emission tomography (PET) imaging to identify poor prognosis patients with a rare form of esophageal cancer.
A small phase II study of 52 patients with stage II and III anal cancer showed that chemotherapy combined with IMRT was as effective but much less toxic compared with the same chemotherapy combined with conventional radiation after 2 years of follow-up.
Conventional radiation plus concurrent 5-fluorouracil and mitomycin-C is the standard of care for non-metastatic anal cancer, but conventional radiotherapy leads to significant toxicity due in part to the large area of the body that is radiated. By contrast, IMRT targets the radiation dose directly to the tumor and lymph nodes affected with cancer but spares healthy adjacent tissues, explained lead author Lisa Kachnic, MD, Boston University. The conformal radiation IMRT delivers is also referred to as “dose painted IMRT.”
Safety and efficacy results of the phase II RTOG 0529 study were compared with historical results from another study by the same group of investigators: RTOG 9811. At a median follow-up of 26.7 months, 2-year disease-free survival (DFS) was 77% and overall survival (OS) was 86% in RTOG 0529 compared with 75% DFS and 91% OS in RTOG 9811. However, use of IMRT resulted in significantly less stage 3 or higher skin and GI toxicity; in fact, grade 3 or higher GI toxicity was 15% less, grade 3 or high skin toxicity was 50% less, and Grade 2 or h igher hematologic toxicity was about 13% less when IMRT was used compared with conventional radiation.
Because 85% of stage II and III patients with anal cancer are cured with radiotherapy plus chemotherapy, researchers have turned their attention to strategies to avoid toxicity, explained session moderator Jennifer Obel, MD. IMRT limits radiation to nearby tissues, which should improve quality of life. If results of this study are confirmed by future studies using IMRT as a treatment platform, “IMRT may emerge as a key treatment modality for anal cancer,” Dr. Obel predicted.
A separate phase II trial found that sorafenib was a valuable third-line strategy in 38 patients with GIST resistant to first-line imatinib and second-line sunitinib. Six patients were resistant to imatinib and 32 were resistant to both drugs. Sorafenib achieved tumor control (i.e., partial response or stable disease) in 68% of patients. One-year survival was 44%, and 2-year survival was 21%.
Sixty-one percent of patients required dose reductions of sorafenib, mainly for hand-foot syndrome and hypertension – two common side effects of this agent.
“Many of these patients whose tumors progressed or worsened on two lines of therapy had nothing left to try. Some of the patients in this study were treated with sorafenib for up to 3 years and did quite well. These results suggest that sorafenib is an additional option,” said lead author Nicholas P. Campbell, MD, University of Chicago, IL. Although sorafenib is not yet approved by FDA as third-line therapy for GIST, NCCN guidelines recommend sorafenib as a third-line option for GIST, and is typically covered by insurers, Dr. Campbell noted.
At the Presscast, Dr. Obel said: “Understanding the mechanisms involved in GIST has allowed great strides in treating this disease, with two new treatments over the past decade. This study suggests that sorafenib is now another option. Patients who progress on imatinib and sunitinib can consider sorafenib as well as enrolling in a clinical trial.”
ColoPrint — an 18-gene signature test — correctly identified patients with stage II colorectal cancer at high risk of progression. Of the 235 patients included in the study, ColoPrint identified 73% as low risk and 27% as high risk. At a median follow-up of 97 months, only 5%of those identified as low risk had a recurrence compared with 20% of those deemed high risk
ColoPrint’s results were independent of the predictive value of most traditional clinical factors associated with recurrence. “There was a clear discordance between ASCO risk factors [e.g, T4, high grade, performance status, <12 lymph nodes assessed) and ColoPrint results, although there was a small degree of overlap. ColoPrint was the only factor to predict distant metastasis in stage II patients,” said lead author Robert Rosenberg, MD, University Hospital, Technical University, Munich, Germany. . ColoPrint could potentially be used to determine which patients can be safely managed without chemotherapy, he noted.
An ongoing prospective, international, multicenter study called PARSC is comparing ColoPrint versus clinical risk factors to predict risk of recurrence in stage II colon cancer.
ColoPrint is investigational, and the price of the test remains to be determined. Another genetic test for stage II colorectal cancer called Oncotype DX is commercially available and costs about $3000. Both tests have the same intent, Dr. Rosenberg explained. A major difference between them is that the 18 genes used in ColoPrint were based on an unselected review of the genome, while Oncotype DX was developed using a candidate gene. ColoPrint is a binary test – identifying low versus high risk — while Oncotype DX discriminates between low, intermediate, and high risk with a lesser degree of sensitivity.
Dr. Obel said, “Both tests help to identify patients at high risk for recurrence, but neither test tells us who will benefit from chemotherapy with 5FU and oxaliplatin. At this point, we know the tests differ based on the way genes and datasets were derived, and ColoPrint is performed on fresh tissue while Oncotype DX is performed on frozen tissue.”
The prospective MUNICON II study found that using positron-emission tomography (PET) imaging to assess response early in the course of chemotherapy is an important prognostic tool for patients with locally advanced cancer of the esophagogastric junction. In the study, 56 patients were treated with 2 courses of chemotherapy and then underwent PET assessment to categorize them as responders (n=33) or non-responders (n=23). Responders continued chemotherapy for 3 additional months before surgery, while non-responders were treated with radiotherapy in hopes of shrinking the tumor size prior to surgery.
Twenty-seven of 33 responders (82%) were able to undergo complete resection versus 16 of the 22 non-responders (70%). At a median follow-up of 38 months, median event-free survival and median OS had not yet been reached in responder, but rates were 15.4 months and 18.3 months, respectively, in non-responders.
PET-guided therapy has been used for other cancers, including lymphoma and lung. According to lead author Florian Lordick, MD, Klinikum Braunschweig, Brunswick, Germany, this is the first study to use early PET results to change treatment strategy in esophageal cancer.
“Unfortunately, our study showed that radiation was not an effective salvage treatment for non-responders. Prognosis in non-responders is still poor because of poor tumor biology,” he said.
The European Organization for Research and Treatment in Cancer (EORTC) plans to use early PET assessment to explore alternative treatment approaches for non-responders, Dr. Lordick said.
By Alice Goodman
By Nancy Ciancaglini
As is the case every year at ASCO, in spite of 4,000 plus studies generated in time for the meeting there are a handful of clinical news stories that really stand-out and grab the attention of researchers, MDs, analysts/investors, and the media. Below, OBR presents a quick overview of what we consider to be the top ten clinical news stories from ASCO 2010. While they correlate pretty well, we usually see a slight difference in what the biggest media stories are and what is most read in OBR daily. To view the most read stories visit the OBR daily News Pulse and find out what others found most interesting at this year’s ASCO.
# 1: Bristol Myers-Squibb’s ipilimumab, a drug designed to enhance the body’s immune system, demonstrated a significant improvement in overall survival in previously-treated advanced melanoma patients in a Phase 3 study. Patients taking ipilimumab lived an average of 10 months compared with 6.5 months for those in a comparison group. (Takes the # 2, # 3, # 5, and # 10 spot in the OBR daily News Pulse)
# 2: In two separate trials, Bristol-Myers Squibb’s Sprycel and Novartis AG’s Tasigna provided newly diagnosed patients with chronic myeloid leukemia (CML) with quicker, better responses as first-line therapies than the gold standard Gleevec, pointing to more favorable long-term outcomes for CML patients. (Figures in the # 2, # 3 and # 7 stories in the OBR daily News Pulse)
# 3: Following front-line therapy with Roche’s Rituxan and chemotherapy, Rituxan maintenance was found to reduce the risk of disease recurrence by 50% in patients with newly diagnosed follicular lymphoma, based on results from the PRIMA study.
# 4: In the Phase 3 GOG 0218 study, adding Roche’s Avastin to initial chemotherapy treatment, and then using it as maintenance therapy in women with advanced ovarian cancer, demonstrated a 39% improvement in the likelihood of women living longer without the disease worsening compared to chemotherapy alone. (Featured in the # 2 most read story in the OBR daily News Pulse)
# 5: In a head-to-head Phase 3 trial of Amgen’s denosumab and Novartis AG’s Zometa, denosumab delayed by 18% the risk of fractures and other bone complications in men with advanced prostate cancer compared with Zometa, the current standard of care for treating cancer patients whose disease has spread to the bone. (Included in the # 2 most ready story in the OBR daily News Pulse)
# 6: Women with advanced breast cancer given Eisai’s experimental chemotherapy drug, eribulin mesylate, derived from a sea sponge, lived longer than those treated with standard cancer therapies—women taking eribulin lived an average of 13.1 months compared to 10.7 months for those receiving conventional cancer treatment.
# 7: In a Phase 2 study, Pfizer’s crizotinib (PF-02341066) reduced tumors in 57% of patients with a rare form of lung cancer caused by a defective ALK gene and stopped the progression of the disease in 87% of patients, providing further clinical evidence in support of personalized cancer treatment.
# 8: In surprising results, Eli Lilly & Co. and Merck KGaA’s Erbitux, successful in treating metastatic colon cancer patients with normal KRAS, failed to prolong survival for patients with early-stage colon cancer (adjuvant) when added to standard treatments. After 16 months follow-up, patients taking Erbitux were actually slightly less likely to survive, with 82% still alive compared with 87% taking chemotherapy alone. (The # 6 most read story in the OBR daily News Pulse)
# 9: Delcath System’s percutaneous hepatic perfusion (PHP) drug delivery system with melphalan extended survival much longer for melanoma patients whose cancer had spread to their liver—patients lived 245 days versus 49 days on best available care.
# 10: In the first, definitive Phase 3 study to show results for patients with advanced medullary thyroid cancer (MTC), AstraZeneca PLC’s vandetanib significantly extended progression free survival (PFS), demonstrating a 54% reduction in the rate of progression compared to placebo.
The July issue of Oncology Business Review will feature more in depth analysis of these important study results. Stay tuned for more.