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Over 30,000 oncologists and other health professionals attended the 2017 American Society of Clinical Oncology annual meeting in Chicago, June 2-6. This year's meeting included several presentations on emerging cancer diagnostic and device treatment strategies, including genetic tests, liquid biopsy systems, radioenhancers, and microspheres intended to improve chemotherapy outcomes.

 

Dividing Breast Cancer Cell


Although the scientific sessions at the 2017 American Society of Clinical Oncology annual meeting were dominated by basic research and drug trials, the meeting also featured many presentations on novel drug-delivery, radiation, and diagnostics technology. Here are some of the highlights of this year's meeting, which was held in Chicago June 2-6.


Myriad's myRisk Test Uncovers Patients At Genetic Risk For Cancer

Results from Study 005, a 2,000-patient prospective study of Myriad Genetics Inc.'s MyRisk hereditary cancer test, showed that more than 50% of the cancer-related mutations identified by the tests were found in patients who do meet the criteria for genetic panel testing under current professional guidelines and 34% of mutations were identified in unexpected genes, which confirms the clinical utility of multi-gene panel testing to improve hereditary cancer-risk assessment, according to the company.


The results of the study led by Gregory Idos, University of Southern California, were the subject of three poster presentations at the ASCO meeting on June 5 and the abstracts are published in the Journal of Clinical Oncology.


All of the patients enrolled in the study met either the standard clinical criteria for genetic testing or were predicted to have at least a 2.5% probability of inherited cancer susceptibility using validated prediction models and assessed them for 25 known cancer-related genetic markers using the MyRisk system. Among the 241 (12.1%) patients who tested positive for a pathogenic mutation, 31.5% had either a BRCA1 or BRCA2 mutation and of those, 68.4% patients had a BRCApro carrier probability greater than 5%. 15.8% patients had a pathogenic mutation in an MMR gene: 19 (50.0%) had an MMRpro carrier probability greater than 5%, while 34.2% had a PREMM1,2,6 carrier probability greater than 5%.


"In a diverse cohort of patients undergoing 25-gene multiple-gene panel testing, half or more carriers of BRCA1/2 or MMR mutations had a CP of < 5%, the consensus guideline-recommended cutoff for genetic testing," Idos et al conclude. "These results support a lower threshold for genetic testing guidelines."


Commenting on this study, Myriad's Chief Medical Officer Johnathan Lancaster, told Medtech Insight:"Panel testing, despite what many payers would like us to believe, is safe and efficacious, and it's for both of those reasons that it has become the standard of care."


"If we continue to use [the existing predictive models] as gatekeepers to access genetic testing, 50% of the mutation carriers are going to be missed," Lancaster said.


"If we continue to use [the clinical guidelines] as gatekeepers to access genetic testing, 50% of the mutation carriers are going to be missed," Myriad's Johnathan Lancaster.


Before the patients were tested with MyRisk, experts predicted which inherited cancer syndromes they expected each patient to have, ranking the top eight most likely, in their estimation. However, 35% of the patients carried pathogenic mutations in genes the experts did not suspect, "suggesting a significant contribution of expanded multiplex testing to clinical cancer risk assessment," Idos et al. wrote. "The identification of off-target mutations broadens our understanding of cancer risk and genotype-phenotype correlations." The study authors are continuing to follow these patients to assess the clinical utility of multiplex gene panel testing.


"You need to use a pan-cancer panel test to maximally identify these mutations," Lancaster said. "The experts in the field [already] realize that you can't predict it. You need to use a panel to identify the optimal number of patients who are carrying these genes."


A separate analysis of Study 005 led by Allison Kurian of Stanford University looked at the potential harm of multiplex testing for cancer risk, such as unwarranted surgery or adverse psychological effects. The analysis found that few of the patients who underwent the multiplex testing in the study had preventative surgery within the next three months and the patients whose tests yielded a so-called "variant of uncertain significance" had no more distress, regret, or uncertainty than patients whose test results were negative for the cancer-related variants. Patients with positive test results most often advised their relatives to undergo similar testing, "suggesting that participants understood the implications of test results," Kurian et al. report.


Nanobiotix' NBTXR3 Nanoparticles Proves Safe In Early Trial

Results of a small phase I trial presented at ASCO show Nanobiotix SA's NBTXR3 functionalized hafnium oxide nanoparticle radioenchancers are safe while results of another trial, also presented at the conference, indicate NBTXR3 injections combined with radiation therapy can help turn a "cold" tumor into a "hot" tumor and help kill the cancer.


NBTXR3's high-electron density of the nanoparticles allows for the absorption and deposition of a high radiation dose within tumor cells undergoing radiation, which Nanobiotix expects will help to kill tumor cells and improve patient outcomes.


On June 5, Christophe Le Tourneau of the Institut Curie in Paris and colleagues presented a poster with results from a phase I trial of NBTXR3-injections and radiation to treat locally advanced head and neck squamous cell carcinoma in 12 patients older than 65 years who could not receive chemotherapy with cisplatin.


There were no serious adverse events or early dose-limiting toxicities. The results showed that a single injection of NBTXR3 provides adequate bioavailability of the nanoparticles over seven weeks of radiation therapy, with no leakage of NBTXR3 to the adjoining healthy tissues. So far, 10 of the patients showed complete or partial response to the therapy.


Seven of the nine patients who received a dose of NBTXR3 equal to at least 10% of the tumor volume showed a complete response and the tumor response suggests a dose dependent effect, Le Tourneau et al. report. The patients treated with dose levels of 15% or 22% have shown a prolongated response with no relapses after a median follow-up of one year. Most of the complete responses were observed three to 10 months after the end of the radiation treatment, but late appearance of tumor complete response as well as "an unusual case of Pseudo Disease Progression" followed by tumor complete response have been observed in the study, according to Nanobiotix.


In May, Nanobiotix announced early results from 26 patients in a randomized trial comparing radiation therapy with or without intratumor injections of NBTRXR3 to treat in soft tissue sarcoma. The study is led by Jerome Galon of the French National Institute of Health and Medical Research in Paris.


Galon et al. collected tumor tissues both before and after the treatment from 14 soft-sarcoma patients who received NBTXR3 and radiation therapy and 12 soft-sarcoma patients who were treated with radiation alone. They also analyzed the immunohistochemistry and digital pathology of the patients for immune biomarkers as well as the patients' gene-expression profile and pre-optimized immune-gene signatures.


Galon et al found that the patients treated with NBTXR3 showed significant increase of T cells and a marked increase of CD103+ immune cell infiltration after the treatment, while no such differences were seen for in the radiation-alone group. The NBTXR3 group also showed increased CD3 + CD8 cell densities after the treatment compared to radiation only group. The up-regulation of pan-immune genes expression, including the expression of adaptive immunity genes between the pre- and post-treatment tests, was more pronounced in the NBTXR3 patients than the radiation-only group, and functional analysis of genes up-regulated in the NBTXR3 group showed an enrichment of cytokine activity adaptive immunity and T cell receptor signaling pathway.


These findings suggest that the NBTXR3 nanoparticle injection "induces a specific adaptive immune pattern," Galon et al. conclude. "As such, it may contribute to convert “cold” tumor into “hot” tumor and be effectively combined with immunotherapeutic agents across oncology."


Chronix' CNI Score Out-Predicts Current Method For Head And Neck Cancer Recurrence

Results of a 54-patient trial presented at the ASCO meeting show Chronix Biomedical Inc.'s copy number instability (CNI) test can be a more accurate predictor of time to cancer progression in patients with head and neck cancer than conventional cancer staging based on clinical parameters.


Given predicted time to progression is an important factor in the therapeutic decision post-surgery, such a test has the potential to improve outcomes in this cancer. "Given predicted-time-to-progression is an important factor in the therapeutic decision post-surgery, such a test has the potential to improve outcomes in this cancer," said lead investigator Julia Beck, a senior scientist with the company.


Chronix believes this test could be used to monitor adjuvant therapy patients at risk for recurrence of head and neck cancer.


Chronix' liquid biopsy system measures copy number instability signatures of cancers with next-generation sequencing of plasma cell-free DNA (cfDNA). Instead of detecting single mutations or rearrangements in the gene, Chronix’s test measures the gains and losses of chromosomal regions in the genome. (Also see "New Chronix Liquid Biopsy Test Could Save Doctors On Immunotherapy Costs" - Medtech Insight, 22 Mar, 2017.)


Currently, human papilloma virus detected in oropharyngeal carcinomas is currently the only prognostic biomarker for this type of tumor, Beck et al. explain in their poster presentation at ASCO on June 5.


The investigators extracted cfDNA from 132 plasma samples from 54 patients with head and neck cancer and calculated CNI scores for each. After unblinding, the investigators evaluated the CNI scores as diagnostic parameter for association with disease characteristics and progression.


The study found that the 29 patients with tumors at stage three or worse and 11 out of 12 patients with stage four tumors had CNI scores over 31, with significantly higher CNI scores seen in patients with stage four tumors. Higher CNI scores were also found in patients with tumor lymph node invasion compared to negative lymph nodes. There was a steep decline of CNI scores after surgical resection and increasing CNI scores in later disease progression.


Also, pre-operative CNI scores proved to be a stronger predictor of time to recurrence than the lymph-node status. Baseline CNIs over 31 strongly correlated with time to recurrence with a median of 20 months and median overall survival of 30 months in the high CNI group. There was no recurrence in the low CNI-score group after five years of follow-up.


The addition of selective internal radiotherapy with Sirtex Medical's SIR-Spheres Y-90 microspheres to first-line chemotherapy did not improve survival of metastatic colorectal cancer patients in the FOXFIRE Combined Analysis.


Sirtex' Sir-Spheres Misses Primary Endpoint

Results of the FOXFIRE Combined Analysis, a composite of three studies, showed that the addition of selective internal radiotherapy with Sirtex Medical's SIR-Spheres Y-90 microspheres to first-line chemotherapy did not improve overall survival or progression-free survival in patients with metastatic colorectal cancer.


Ricky Sharma from University College London presented the results, which combine the data from the SIRFLOX, FOXFIRE, and FOXFIRE-Global studies, at the ASCO meeting on June 5. The combined analysis of 1,103 patients is the largest cancer study ever conducted to investigate the combination of chemotherapy with an interventional radiology procedure, Sharma said. (Also see " CLINICAL CORNER: SIR-Spheres Improve Liver Chemotherapy; REVISE Supports Viabahn AV Endoprosthesis over PTA " - Medtech Insight, 4 Jul, 2016.)


All three studies enrolled patients with metastatic colorectal cancer with liver metastases not suitable for curative resection/ablation who never had chemotherapy before. The combined analysis had two arms: Patients treated with either oxaliplatin-based chemotherapy with or without an investigator-chosen biologically targeted agent; and patients treated with the same systemic therapy plus a single treatment with SIR-Spheres and one or two cycles of chemotherapy. Median follow-up 43.3 months.


There were a total of 844 deaths and no difference in overall survival or progression-free survival between the two arms of the study, but the response rate and liver-specific progression were significantly more favorable in the arm treated with SIR-Spheres, but that group had higher risk of non-liver progression as the first event and severe or life-threatening adverse events were slightly more common in the SIR-Spheres-treated group than the chemotherapy-alone group. There were no differences in patient health status questionnaire scores between the groups.


An exploratory subgroup analysis of the studies showed a strong signal indicating that the addition of SIR-Spheres may have improved overall survival in patients with right-sided primary colon tumors, which would increase the median overall survival by 4.9 months and reducing the risk of death in this group at any timepoint by 36%.


"This unexpected finding may prove to be clinically meaningful, as patients with right-sided primary colon tumors represent more than a third of all colon cancer patients," Sharma said. "They have a very poor prognosis compared to patients with other colorectal cancers, which represents a major unmet medical need and an important focus of cancer research today." A more detailed analysis of the primary tumor location in the SIRFLOX and FOXFIRE Global studies will be available at the European Society for Medical Oncology World Congress of Gastrointestinal Cancer, June 28 to July 1 in Barcelona, according to Sirtex.

 

 

Angle’s Parsortix System Isloates CTCs From Metastatic Colorectal Cancer

ANGLE PLC's Parsortix circulating tumor cell (CTC) harvesting system successfully analyzed CTCs for the presence or absence of arginine methylation of the epidermal growth factor receptor (meEGFR) in the first study of meEGFR-status across a population of circulating tumor cells isolated from colorectal cancer patients being treated with epidermal growth factor receptor (EGFR) inhibitors.


Krittiya Korphaisarn of the University of Texas MD Anderson Cancer Center in Houston and colleagues presented results of the 47-patient study as a poster on June 3 at the ASCO meeting.


Previous research has already established meEGFR-status as a predictor of a patient’s response to EGFR- inhibitors, so this study was designed to see if the presence of meEGFR biomarker in CTCs could predict an adverse duration of progression-free survival in the treatment group.


The study found that the total number of CTCs harvested was not correlated to progression free survival, but that the proportion of those CTCs that had the meEGFR marker was predictive. The patients whose CTCs harvested by Parsortix had a higher proportion of meEGFR positive CTCs had significantly shorter progression free survival than the patients whose CTCs had lower levels of meEGFR. "Assessment of meEGFR-CTCs may provide a 'liquid biopsy' biomarker for reduced efficacy from anti-EGFR drugs," Korphaisarn et al. conclude.


"This study is a further demonstration of the effectiveness of Parsortix in enabling liquid biopsy analysis of patients’ cancer through a simple blood test with the potential to provide clinically relevant information to advise treatment decisions," ANGLE says.

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