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Sunday, January 20, 2019

Game theory can bring humans and robots closer together


Researchers at the University of Sussex, Imperial College London and Nanyang Technological University in Singapore have for the first time used game theory to enable robots to assist humans in a safe and versatile manner.
The research team used adaptive control and Nash equilibrium game theory to programme a robot that can understand its human user’s behaviour in order to better anticipate their movements and respond to them.
The researchers believe the breakthrough could help robots complementing humans for sport training, physical rehabilitation or shared driving.
Lead author Dr Yanan Li, Lecturer in Control Engineering at the University of Sussex, said: “It is still very early days in the development of robots and at present, those that are used in a working capacity are not intuitive enough to work closely and safely with human users. By enabling the robot to identify human users’ behaviour and exploiting game theory to let the robot optimally react to them, we have developed a system where robots can work along humans as humans do.”
In a paper published today in Nature Machine Intelligence, the researchers outline how they adapted game theory for the physical interaction of a robot with a human, and how this can be used to help an impaired stroke survivor retrain their motor control.
Game theory is commonly used to understand how economic agents decide and interact with each other in order to maximise their own gain. To successfully apply game theory to the interaction of a robot and its human user, the researchers had to overcome the issue that the robot cannot know the human’s intentions. The researchers thus had to develop a method enabling the robot to identify the human partner while safely and efficiently interacting with their motion.
The reactive robotic programming system enables a robot to continuously learn the human user’s control and adapt its own control correspondingly. The robot is able to understand the human user’s action and then respond to and assist them to perform tasks successfully and with minimal effort.
Professor Etienne Burdet, Chair in Human Robotics in the Department of Bioengineering at Imperial College London and senior author of the paper, added: “Game theory has had important impacts in economics during the last century and lead to several Nobel prizes such as Nash’s one. To apply it for human-robot interaction, it was necessary to understand how the robot can identify the human user’s control goals simultaneously to smoothly interacting with them.”
Story Source:
Materials provided by University of Sussex. Original written by Neil Vowles. Note: Content may be edited for style and length.
Journal Reference:
  1. Y. Li, G. Carboni, F. Gonzalez, D. Campolo, E. Burdet. Differential game theory for versatile physical human–robot interaction. Nature Machine Intelligence, 2019; 1 (1): 36 DOI: 10.1038/s42256-018-0010-3
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Body-painting protects against bloodsucking insects


Striped bodypaint was the most protective.
Credit: Gabor Horvath
A study by researchers from Sweden and Hungary shows that white, painted stripes on the body protect skin from insect bites. It is the first time researchers have successfully shown that body-painting has this effect. Among indigenous peoples who wear body-paint, the markings thus provide a certain protection against insect-borne diseases.
Most of the indigenous communities who paint their bodies live in areas where there is an abundance of bloodsucking horseflies, mosquitoes or tsetse flies. When these insects bite people there is a risk of bacteria, parasites and other pathogens being transferred.
The study shows that body-painting provides protection against the insects. A brown plastic model of a human attracted ten times as many horseflies as a dark model painted with white stripes. The researchers also found that a beige-coloured plastic figure used as a control model attracted twice as many bloodsuckers as the striped model.
According to Susanne Åkesson, professor at Lund University’s Department of Biology, the tradition of body-painting may have developed simultaneously on different continents. It is not known when the tradition started.
“Body-painting began long before humans started to wear clothes. There are archaeological finds that include markings on the walls of caves where Neanderthals lived. They suggest that they had been body-painted with earth pigments such as ochre,” says Susanne Åkesson.
The research team has previously observed that the zebra’s stripes act as protection against horseflies. It is also known that pale fur, on horses for example, can provide protection, in contrast to dark fur. The discovery won the IgNobel Prize in Physics in 2016. In the new study, the team has taken the research a step further and examined plastic models that are the same size as adult humans.
For the experiments, which were conducted in Hungary, the researchers painted three plastic models of humans: one dark, one dark with pale stripes and one beige. They then covered the three models with a layer of insect glue. The dark model attracted ten times more horseflies than the striped model, and the beige model attracted twice as many as the striped one.
They also examined whether the attraction of horseflies differed between models that were lying down or standing up. The results show that only females were attracted to the standing models, whereas both males and females were drawn to the supine models.
“These results are in line with previous experiments in which we showed that males gravitate towards water in order to drink and land on surfaces that reflect horizontal, linear polarised light, such as signals from a water surface. Females that bite and suck blood from host animals respond to the same signals as the males, but also to light signals from in the vertical plane, such as the standing models,” concludes Susanne Åkesson.
Story Source:
Materials provided by Lund University. Note: Content may be edited for style and length.
Journal Reference:
  1. Gábor Horváth, Ádám Pereszlényi, Susanne Åkesson, György Kriska. Striped bodypainting protects against horseflies. Royal Society Open Science, 2019; 6 (1): 181325 DOI: 10.1098/rsos.181325
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Why haven’t cancer cells undergone genetic meltdowns?


Cancer first develops as a single cell going rogue, with mutations that trigger aggressive growth at all costs to the health of the organism. But if cancer cells were accumulating harmful mutations faster than they could be purged, wouldn’t the population eventually die out?
How do cancer cells avoid complete genetic meltdown?
To get at the heart of the matter, a team of scientists from Beijing and Taipei wanted to get a new hint at cancer vulnerability from a mutational perspective by probing the most famous cultured cancer cells, HeLa cells.
Famously isolated from cervical cancer victim Henrietta Lacks in 1951, they became the first immortalized cell line, helped in the development of the polio vaccine, and have become a biotechnology foundational resource for any in vitro drug development or cancer studies.
And they are still providing ample opportunities to further our understanding of cancer.
“In this study, HeLa cells are not used to reveal the process of tumorigenesis but mainly a model for addressing the underlying evolutionary forces, which need to be powerful enough to measure in laboratory settings. We examined variation in growth rate among individual HeLa cells by monitoring clones from a common ancestral HeLa cell population,” said corresponding author Xuemei Lu.
They first established a HeLa cell line (E6) derived from an ancestral cell line. When the population size of E6 reached approximately 5 × 104 cells (15~16 divisions), five single-cell clones were generated and established in culture. They team DNA sequenced these clones to catalog the mutations. They focused on copy number variation (CNV) rather than single DNA changes because single-nucleotide mutation rates are too slow to produce significant sequence variation during the short-duration culturing experiments.
“We then estimated the deleterious mutation rate and the average fitness decrease per mutation by performing computer simulations of cell growth,” said author Hurng-Yi Wang.
Overall, they found that the main mutations affect the copy number of genes, with an average of 0.29 deleterious events for every cell division. Each of these events reduces fitness 18 percent.
Their results indicate that heterogeneity in cell growth can be generated in a very short period of time in cancer cells and is heritable and genetically determined.
“Our estimates indicate that the HeLa cells experience a 5 percent reduction (0.29 ×0.18 ? 5%) in fitness for every generation. Our observations suggest that human cells that have been cultured for a sufficiently long period still generate deleterious mutations in the form of CNVs at a high rate and with a high intensity. For such systems, a mutational meltdown might be plausible.”
For example, when they isolated 39 cells from B8 (a fast-growing clone) and 40 cells from E3 (slow growing clone), and monitored their growth from a single cell for seven days, approximately 23 percent of B8 and 50 percent of E3 cells died out within seven days, due to either damage caused during cell isolation or genetic defects.
Most cell lines with growth rates < 0.6 died within 2 months. In total, only 60 percent of B8 and 27 percent of E3 cells survived for more than two months.
Next, they picked about 20 cells from each of the single cell originated clones from B8 and counted their chromosome numbers.
The chromosomes varied far from the normal human number of 46. They ranged from 38 to 113 chromosomes, with most (72 percent) cells harboring between 55 and 70 chromosomes, indicating that they are triploid. Therefore, despite single-cell origin, the progeny quickly generated aneuploidy within only 20-30 cell divisions, again illustrating frequent cytogenetic change in cancer cells.
Despite the level of mutations occurring, reduction in growth rates, and chromosome numbers no longer representing that of normal humans, cancer cells still find a way to survive.
So how do HeLa cells persist?
“High deleterious mutation rate would raise an impression that the HeLa cell lines may have gone extinct long ago,” said Lu.
Their simulation results indicated that although most of the cells accumulated deleterious mutations and were worse than the ancestral cells, there were still 13.1 percent of cells which were mutation-free.
“These mutation-free cells can avoid the population from extinction.”
It also explains why, even if chemotherapy treatment successfully killed 90 percent of a cancer cell population, it may still not be enough.
The new study not only advances the understanding of the evolution of HeLa cells, and of tumors in general, but of the cells of multicellular organisms in culture in general. In future work, the scientists want to exploit their cancer cell fitness and growth rate findings to understand how cancer cells can become even more vulnerable to recent breakthroughs with checkpoint inhibitor drugs.
Story Source:
Materials provided by Molecular Biology and Evolution (Oxford University Press). Note: Content may be edited for style and length.
Journal Reference:
  1. Yuezheng Zhang, Yawei Li, Tao Li, Xu Shen, Tianqi Zhu, Yong Tao, Xueying Li, Di Wang, Qin Ma, Zheng Hu, Jialin Liu, Jue Ruan, Jun Cai, Hurng-Yi Wang, Xuemei Lu. Genetic Load and Potential Mutational Meltdown in Cancer Cell Populations. Molecular Biology and Evolution, 2019; DOI: 10.1093/molbev/msy231
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Spectrum empties marketed portfolio worth $300M to deal-hungry Aurobindo


Buzz of a potential sale at Spectrum Pharma first emerged last June. As it turns out, the rare disease and cancer specialist is indeed pulling off a transaction—but only for its FDA-approved products.
Spectrum is selling its entire portfolio of seven marketed products to Acrotech Biopharma, a wholly-owned subsidiary of India’s Aurobindo, the Nevada-based company announced Thursday. In exchange, Spectrum will get $160 million upfront and up to $140 million in regulatory and sales-based milestones.
As a result, the company will cast aside about 40% of its workforce—or about 90 by its 2017 end-of-year tally of 215—with most of them slated to move to New Jersey-based Acrotech, “thereby right-sizing Spectrum for our development efforts,” Spectrum president and CEO, Joe Turgeon, said in a statement Thursday.
To hear Turgeon tell it, the selloff is a strategic shift “to ensure laser-focus” on novel oncology drugs, and the cash is placing Spectrum “in a solid position to evaluate additional growth opportunities.”
Spectrum just recently strengthened its development force, having poached Ziopharma Oncology’s executive vice president of R&D, Francois Lebel, M.D., as its chief medical officer. But the castoff doesn’t mean Spectrum is abandoning commercial operations altogether. The company is keeping “a core group of commercial talent” in anticipation of the launch of two late-stage drugs.

Designed to reduce the duration of severe neutropenia in breast cancer patients treated with chemotherapy, Rolontis’ biologics license application is already on the FDA waiting list. In two phase 3 studies, the drug matched Amgen’s Neulasta in improving an abnormally low count of white blood cell neutrophils.
TKI inhibitor poziotinib, which targets EGFR and HER2 exon 20-mutant cancer, is the other near-term focus at Spectrum. However, despite somewhat encouraging midstage data in metastatic non-small cell lung cancer, the FDA recently turned down poziotinib’s application for a “breakthrough” designation, meaning an expedited review is currently off the table. At that time, Turgeon said the firms’ plan and commitment to the program remains unchanged, and that it will continue to work with the FDA “to achieve the fastest route to approval” based on the phase 2 data.
On the castoff board are seven already-approved products in oncology and hematology, including a folate analog called Khapzory that just nabbed an FDA nod in October. Together, these products generated sales of $76.4 million in the first nine months of 2018.
With blessings from both companies’ boards, the transaction is expected to close within 90 days, pending regulatory approvals.

For Aurobindo, it marks yet another purchase in just a few months. In September, the Indian drugmaker signed a deal with Novartis, obtaining about 300 products and development projects in its Sandoz U.S. generic oral solids and dermatology business for $900 million upfront. Shortly before that, Aurobindo expanded in Europe, acquiring Apotex’s commercial operations in five European countries, in a deal that added more than 200 generics and more than 80 OTC products to its European portfolio. Then, in November, it announced a pact to acquire “an under-development product and certain related assets” from Australia’s Advent Pharma for $12.5 million.
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‘Impressive’ Activity in Biliary Cancer with Combo Therapy


A precision-medicine treatment strategy showed “impressive” activity in patients with a rare but aggressive biliary tract cancer, according to a study reported here.
The combination of dabrafenib (Tafinlar) and trametinib (Mekinist) led to objective responses in about 40% of patients with BRAF-mutated biliary tract cancer. An additional 40-45% of 33 evaluable patients had stable disease.
“Nearly every patient had some tumor reduction,” said Zev Wainberg, MD, of the University of California Los Angeles, at the Gastrointestinal Cancers Symposium. “The duration of response at 6 months was 66%. Many of the patients who had stable disease also had durable clinical benefit.”
The cohort had a median progression-free survival (PFS) exceeding 9 months and a median overall survival (OS) of almost a year, he added. The safety profile of dabrafenib/trametinib was consistent with previously reported clinical experience.
The results are “incredibly impressive,” said Heinz-Josef Lenz, MD, of the University of Southern California Norris Cancer Center in Los Angeles.
“I think it is important to recognize that most of these patients were heavily pretreated,” he said. “I don’t think I need to convince you that this treatment is very effective.”
Given the multiple potentially actionable mutations in biliary tract cancer, the study could represent just the first step toward expanded and more effective treatment options for the aggressive disease, Lenz added. Better understanding of the tumor microenvironment — particularly signaling between normal tissue, stromal tissue, and tumor tissue — should provide insights to inform development of new therapeutic strategies.
Multiple mutations have been identified in association with biliary cancer, including BRAF in about 5% of tumors overall, perhaps more often in intrahepatic tumors, Wainberg continued. Previous studies of dabrafenib/trametinib, which simultaneously inhibits BRAF and MEK, demonstrated activity in several types of cancer associated with the BRAF V600E mutilation , including melanoma, non-small cell lung cancer, and anaplastic thyroid cancer.
Wainberg reported findings from the biliary cancer cohort of phase II ROAR trial, which evaluated the dabrafenib/trametinib combination in multiple types of advanced rare cancer associated with BRAF V600E. The biliary cancer subgroup included 35 patients, most of whom had received two or more prior lines of therapy.
The median duration of exposure to dabrafenib/trametinib was 6 months and ranged to 32 months. All but five patients continued study medication for more than 3 months. The trial had a primary endpoint of investigator-assessed response.
Among 33 evaluable patients, 14 (42%) had partial responses with the combination therapy. An independent review committee concluded that 12 (36%) patients achieved objective responses. An additional 15 patients had stable disease by investigator assessment, 13 by independent review. Both reviews found that four patients had progressive disease as best overall response. Two patients were not evaluable, according to the independent review committee.
About a third of patients received one or more additional treatments after dabrafenib/trametinib, including chemotherapy, surgery, small-molecule inhibitors, immunotherapy, biologic therapy, and radiation therapy.
The biliary cancer cohort had a median PFS of 9.2 months by investigator assessment. Median OS was 11.7 months.
N0 new or unexpected adverse events occurred during treatment with dabrafenib/trametinib. The most commonly reported treatment related adverse events were pyrexia (40%); rash (29%); nausea, diarrhea, and fatigue (23% each); and chills (20%). Adverse events leading to dose reduction occurred in 37% of patients and adverse events leading to dose interruption in 54%. One patient (3%) had an adverse event that led to permanent discontinuation.
Two patients died of sepsis, but neither death was considered treatment related, said Wainberg.
Genetic analysis of tissue samples from 16 patients yielded findings consistent with previously reported observations about the genetic landscape of biliary tract cancer. Tumor mutational burden was low (<6 mut/Mb) in all evaluable patients.
“These results represent the first prospectively analyzed cohort of patients with BRAF V600-mutant biliary tract cancer treated with the combination of BRAF and MEK inhibitors,” Wainberg concluded. “Dabrafenib and trametinib demonstrated clinical benefit in patients with BRAF-mutant biliary tract cancer and should be considered a meaningful therapeutic option for these patients. BRAF V600 is an actionable driver mutation and should be considered for routine testing in patients with biliary tract cancer.”
The ROAR basket trial was supported by Novartis.
Wainberg disclosed relevant relationships with Aduro Biotech, Array BioPharma, Bristol-Myers Squibb, Five Prime Therapeutics, Genentech, Lilly, Merck, Merck KGaA, Novartis, Sirtex Medical, Pfizer, and Plexxikon.
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Mixed Results with Immune Therapy in Advanced, Refractory Colon Cancer


Immune therapies continued to achieve limited success in the treatment of microsatellite stable (MSS) refractory or advanced colorectal cancer (CRC), according to studies presented here.
In a study of 180 patients with advanced, refractory CRC, the combination of PD-L1 inhibitor durvalumab (Imfinzi) plus a monoclonal antibody against CTLA-4, tremelimumab extended overall survival (OS) to a median of 6.6 months (hazard ratio 0.72, (90% CI 0.54-0.97, P=0.07) compared with a median of 4.1 months for best supportive care (BSC), reported Eric Chen, MD, PhD, University Health Network in Toronto, and colleagues.
But the combination had no effect on progression-free survival (PFS) at 1.8 months (90% CI 1.8-1.9 months) versus 1.9 months (90% CI 1.8-1.9 months) for BSC, Chen said in a presentation at Gastrointestinal Cancers Symposium (GICS).
In a separate study of 121 patients in stage IV CRC limited to liver metastases, tecemotide (L-BLP25), a vaccine that targets the MUC1 antigen, failed to have any effect on either recurrence-free survival (RFS) or OS, regardless of the level of MUC1 expression, reported Carl Schimanski, MD, PHD, on Klinikum Darmstadt in Germany, and colleagues.
“A number of large clinical trials looking at anti-PD-L1 inhibitor monotherapy, or anti-PD-L1 inhibitors given in various combinations, have all been negative in microsatellite stable CRC, and even if you select patients for PD-L1 positivity, none of the MMS patients have responded to anti-PD-1 therapy, so single agent treatment has not been successful in this population,” said GICS discussant Michael Overman, MD, of MD Anderson Cancer Center in Houston.
And while he did not totally dismiss the potential benefit of treating refractory CRC with the combination of durvalumab plus tremelimumab, “I think we need confirmation of these findings to have confidence in them before this data is incorporated into any clinical practice,” Overman stated.
As for the anti-cancer vaccine, tecemotide, here again, “all trials have been negative in regards to their primary OS endpoint,” he said.
Thus, oncologists continue to confront challenges in the use of immune therapy in the treatment of MMS CRC, Overman said.
The Canadian CO.26 trial randomized patients with advanced CRC who had failed all standard CRC regimens to either IV durvalumab (1500 mg) every 28 days along with IV tremelimumab (75 mg) given on day 1 for the first four cycles plus BCS (n=119) or BCS alone (n=61). Over 85% of patients received at least 90% of planned doses of the active therapy arm, Chen reported.
At a median follow-up of 15.2 months, no complete responses (CRs) were observed in either arm and there was only one partial response (PR) in the combination arm. On the other hand, the disease stabilized in 22.7% of patients on the combination strategy compared with only 6.6% of those treated with best supportive care (P=0.006). Rates of grades 3 and 4 abdominal pain, fatigue and lymphopenia were all significantly higher in the active therapy arm compared with BSC (P<0.01).
Nevertheless, Chen suggested that quality of life was not adversely affected by this particular regimen, and that “Results from this study suggest that the combination of durvalumab and tremelimumab prolongs overall survival of patients with refractory colorectal cancer compared to best supportive care.”
He added that “this is the first study demonstrating immune checkpoint blockade effectiveness in colorectal cancer patients unselected for mismatch repair deficiency.” Colorectal tumors are classified according to their global genomic status, either microsatellite instable (MSI) or MMS. MSI is the molecular fingerprint of a mismatch repair deficiency, where immune checkpoint blockade has demonstrable activity.
In the second trial, Schimanski noted that 79 patients with stage IV CRC limited to liver metastases received tecemotide after undergoing resection of both the primary tumor and liver metastases (R0/R1). The vaccine was given as eight weekly, subcutaneous injections followed by 6-week maintenance intervals, until recurrence or a maximum of 2 years. Three days prior to the first tecemotide dose, patients were treated with cyclophosphamide at a dose of 300 mg/m2 to reduce regulatory T-cells.
The remaining 42 patients served as placebo controls. At a median of 6.1 months in the tecemotide arm and 11.4 months in the placebo arm, RFS rates were not significantly different between the twp groups. Similarly, OS rates for patients treated with tecemotide were 62.8 months (45.1 months-not achieved or NA) compared with NA (53.6 months to NA) for placebo controls, a difference which was again not statistically significant between the two groups.
However at 3 years, 69.1% of patients in the vaccine arm and 79.1% of patients in the control arm were still alive. prompting Schimanski to suggest that “the unexpectedly high OS rate highlights the critical importance of both accurate staging and intensive surveillance.”
The CO.26 trial was funded by AstraZeneca.
Chen disclosed support from AstraZeneca, Merck, Bristol-Myers Squibb (BMS), Novartis, Boston Biomedical and Seattle Genetics, as well as relevant relationships with Taiho, Eisai, reiStone, and PMRI.
Schimanski disclosed support from Merck KGaA.
Overman disclosed support from BMS, MedImmune, Merck, and Roche, as well as relevant relationships with BMS, Gritstone Oncology, MedImmune, and Roche/Genentech.
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Metastatic Gastric Ca Treatments Show Mixed Results


Mixed results emerged from studies evaluating the efficacy of two novel therapies for patients with metastatic gastric cancer, researchers reported.
In one study, trifluridine/tipiracil (FTD/TPI, Lonsurf) was shown to be an effective treatment option for patients with metastatic gastric cancer, regardless of prior gastrectomy.
In the other, the monoclonal antibody andecaliximab plus the chemotherapy regimen mFOLFOX6 (mFOLFOX + ADX) as a first-line treatment in patients with advanced gastric or gastroesophageal junction adenocarcinoma failed to improve overall survival.
Both studies were presented here at the 2019 Gastrointestinal Cancers Symposium.
TAGS Trial
According to David H. Ilson, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York City, who presented the study on FTD/TPI, the only potentially curative treatment for early stage gastric cancer is surgery, with 5-year survival rates after gastrectomy of 90% or more in Japan and Korea and 40% to 75% in non-Asian countries.
Furthermore, the disease recurs in up to half of patients, while 40% of patients with metastatic disease have had a previous gastrectomy.
The phase III TAGS study had demonstrated that FTD/TPI is effective and safe for patients with heavily pretreated metastatic gastric cancer. Here, Ilson and his colleagues evaluated the efficacy and safety of the FTD/TPI in patients with or without gastrectomy.
Patients were randomized two-to-one (337 in the FTD/TPI arm and 170 in the placebo arm) to receive FTD/TPI (35 mg/m2 BID on days 1–5 and 8–12 of each 28-day cycle) or placebo.
Of the 507 patients in the study, 147 in the FTD/TPI arm had a prior gastrectomy compared to 74 in the placebo arm.
In the total study population, median overall survival was 5.7 months in the FTD/TPI arm compared to 3.6 months in the placebo arm (HR 0.69). Progression-free survival was 2.0 vs 1.8 in the FTD/TPI and placebo arms, respectively (HR 0.57).
The overall and progression-free survival data of patients with prior gastrectomy “mirrored the data seen in the overall treatment population,” Ilson reported, with overall survival improving by 2.6 months in the FTD/TPI arm (HR 0.57).
As for safety, hematologic adverse events such as neutropenia/leukopenia were more frequent among those patients treated with FTD/TPI, but these did not lead to more frequent treatment discontinuation.
“I think the data from this study reinforce the benefit of TPI as prolonging survival versus placebo, regardless of gastrectomy,” Ilson concluded.
Combination Treatment
In a prior phase I/IB study, the combination of mFOLFOX6 and ADX “revealed encouraging anti-tumor activity in patients with gastric or gastroesophageal junction adenocarcinoma,” noted Manish A. Shah, MD, of Weill Cornell Medicine in New York City.
He presented a phase III, randomized, double-blind, multicenter study comparing the efficacy and safety of mFOLFOX with or without ADX in patients with untreated HER2-negative gastric or gastroesophageal junction adenocarcinoma.
From September 2015 to May 2017, 432 patients were randomized to receive either mFOLFOX plus ADX (218) or mFOLFOX with placebo (114).
The primary endpoint was overall survival, with secondary endpoints of progression free survival, objective response rate, and safety.
As for statistical assumptions regarding overall survival, “we were aggressive,” said Shah. “We wanted to demonstrate a real improvement in benefit with andecaliximab, so we were hoping to improve overall survival from 11.5 months to 16.4 months.”
However, Shah reported, “disappointingly, we didn’t see an improvement in survival with ADX.”
Overall survival was a median of 12.5 months (95% CI 11.2-14.0), compared to 11.8 months (95% CI 10.3-13.5) in the ADX and placebo groups, respectively (HR 0.93).
Median progression-free survival was 7.5 months compared to 7.1 months in the ADX and placebo groups, respectively (HR 0.84), while the overall response rate was 50.5% vs 41.1% in the ADX and placebo groups, respectively.
Adverse events were comparable in the two groups, with the most frequent being nausea, diarrhea, neutropenia, and fatigue.
Shah did note that elderly patients — 65 and older — did better on ADX than other subgroups. Median overall survival in that group was 13.9 months compared to 10.6 months in the placebo group, while progression-free survival was 8.7 months compared to 6.5 months.
The apparent increased activity of the combination of mFOLFOX with ADX in patients ages 65 or older needs further study, Shah said.
Shah disclosed institutional research funding from Boston Biomedical, Gilead Sciences, Merck, and Oncolys BioPharma.
Ilson disclosed consulting or an advisory role with AstraZeneca, Bayer, Bristol-Myers Squibb, Lilly/ImClone, Merck, Pieris Pharmaceuticals, and Roche/Genentech.
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