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Findings of a new study have revealed that pancreatic cancer can be divided into four distinct subtypes. Using whole-genome sequencing and copy-number variation analysis on 100 primary pancreatic ductal adenocarcinomas, the authors categorised tumours by the nature of their genomic disruption. 20% of the cohort had stable tumours, containing fewer than 50 structural variations. 30% of patients had locally rearranged tumours, which showed a significant focal event on one or two chromosomes. Scattered tumours (36%) were characterised as having less than 200 structural variations, whereas unstable tumours (14%) contained more than 200 structural variations. Patients with unstable tumours were more likely to respond to platinum-based therapy, and these findings suggest a potential surrogate
biomarker. “We already know that BRCA pathway mutations can cause genomic instability”, explains Sean Grimmond (Wolfson Wohl Cancer Research Centre, University of Glasgow, Glasgow, UK), corresponding author of the study. “In some patients, we saw scarring of the genome that suggested that kind of damage, and many of these patients had somatic or germline mutations”. For patients with unstable tumours, the instability was often related to the BRCA pathway. Patients with unstable tumours were more likely to respond to platinum-based therapy. “We can select patients based on this molecular abnormality to receive treatments... that exploit this specific genomic vulnerability”, comments Philip Philip (Wayne State University, Detroit, MI, USA). He cautions that development of new therapies for pancreatic cancer might be slow. “Where you have
multiple gene mutations, you still have to know which are the important ones—you can’t just prescribe a drug to match a mutation and expect the treatment to work well”, he says. Grimmond’s study confirmed that six genes are commonly mutated in pancreatic cancer, including three tumour suppressor genes that are proving very difficult to target. The locally rearranged tumours offer some hope. In more than half of these cases, the majority of the damage was done to a single chromosome. “Those events lead to an amplification of an oncogene. If we look at the genes within those regions, we start to see things like ERRB2, a target in the treatment of gastric cancer”, adds Grimmond. Under the damaged surface of the genome, there might be druggable targets.
Maurizio De Angelis/Science Photo Library
Whole-genome analysis of pancreatic cancer
Published Online March 6, 2015 http://dx.doi.org/10.1016/ S1470-2045(15)70085-9 For the study by Waddell and colleagues see Nature 2015; published online February 25. http://www.nature.com/nature/ journal/v518/n7540/full/ nature14169.html
Talha Khan Burki
On March 6, 2015, Zarxio (filgrastimsndz) became the first biosimilar product to receive approval from the US Food and Drug Administration (FDA). Manufactured by Sandoz, a subsidiary of Novartis, Zarxio is biosimilar to Amgen’s Neupogen (filgrastim), a myeloid growth factor. Zarxio was approved by the European Union in 2009, under the name Zarzio, and its transatlantic approval is for the same indications as Neupogen. Amgen has initiated legal proceedings; its request for a temporary injunction will be heard on March 13, 2015. Peter Johnson (Southampton University, Southampton, UK) welcomes the FDA’s decision. “It could mean fewer regulatory hurdles for new biological drugs to reach the market, avoid needless reduplication of clinical trials, increase competition and drive down costs”, he explains. The approval came www.thelancet.com/oncology Vol 16 April 2015
under an expedited licensing process, during which biosimilar drug trials are not expected to provide a full complement of preclinical and clinical data; the regulator can use evidence from the reference product (in this case Neupogen) to guide its decision. Johnson notes that questions remain over how similar a drug must be to qualify for this process and the circumstances under which new clinical trials would be required. “NICE have some existing guidance on appraising biosimilar drugs, but this principle has yet to be put to the test here in the UK”, adds Johnson. The crucial point is that similar does not mean identical. “The goal is to have biosimilars that reach the market place reasonably quickly”, explains Gary Lyman Lyman (University of Washington, Seattle, WA, USA). “The challenge is establishing a level of safety and efficacy with which
clinicians are comfortable.” Postmarket monitoring will be important to capture any delayed or uncommon adverse events. The market itself will be largely shaped by the response of private insurers and Medicare to the advent of biosimilar drugs. Express Scripts, a US pharmacybenefit management organisation, estimates that introduction of Zarxio could reduce US drugs costs by around US$5·7 billion in the next 10 years. If 11 other biosimilar drugs in development enter the American market, Express Scripts estimates a further $250 billion could be saved. Lyman is optimistic: “my guess is that within 5 years, we’ll have a broader acceptance of biosimilars, they’ll be regularly used in the USA, and healthcare costs will be brought down”, he concludes.
Chassenet/Bsip/Science Photo Library
First biosimilar drug approved in the USA
Published Online March 13, 2015 http://dx.doi.org/10.1016/ S1470-2045(15)70088-4 For the press release by US Food and Drug Administration see http://www.fda.gov/ NewsEvents/Newsroom/ PressAnnouncements/ ucm436648.htm
Talha Khan Burki e161
Findings of a new study have revealed that pancreatic cancer can be divided into four distinct subtypes. Using whole-genome sequencing and copy-number variation analysis on 100 primary pancreatic ductal adenocarcinomas, the authors categorised tumours by the nature of their genomic disruption. 20% of the cohort had stable tumours, containing fewer than 50 structural variations. 30% of patients had locally rearranged tumours, which showed a significant focal event on one or two chromosomes. Scattered tumours (36%) were characterised as having less than 200 structural variations, whereas unstable tumours (14%) contained more than 200 structural variations. Patients with unstable tumours were more likely to respond to platinum-based therapy, and these findings suggest a potential surrogate
biomarker. “We already know that BRCA pathway mutations can cause genomic instability”, explains Sean Grimmond (Wolfson Wohl Cancer Research Centre, University of Glasgow, Glasgow, UK), corresponding author of the study. “In some patients, we saw scarring of the genome that suggested that kind of damage, and many of these patients had somatic or germline mutations”. For patients with unstable tumours, the instability was often related to the BRCA pathway. Patients with unstable tumours were more likely to respond to platinum-based therapy. “We can select patients based on this molecular abnormality to receive treatments... that exploit this specific genomic vulnerability”, comments Philip Philip (Wayne State University, Detroit, MI, USA). He cautions that development of new therapies for pancreatic cancer might be slow. “Where you have
multiple gene mutations, you still have to know which are the important ones—you can’t just prescribe a drug to match a mutation and expect the treatment to work well”, he says. Grimmond’s study confirmed that six genes are commonly mutated in pancreatic cancer, including three tumour suppressor genes that are proving very difficult to target. The locally rearranged tumours offer some hope. In more than half of these cases, the majority of the damage was done to a single chromosome. “Those events lead to an amplification of an oncogene. If we look at the genes within those regions, we start to see things like ERRB2, a target in the treatment of gastric cancer”, adds Grimmond. Under the damaged surface of the genome, there might be druggable targets.
Maurizio De Angelis/Science Photo Library
Whole-genome analysis of pancreatic cancer
Published Online March 6, 2015 http://dx.doi.org/10.1016/ S1470-2045(15)70085-9 For the study by Waddell and colleagues see Nature 2015; published online February 25. http://www.nature.com/nature/ journal/v518/n7540/full/ nature14169.html
Talha Khan Burki
On March 6, 2015, Zarxio (filgrastimsndz) became the first biosimilar product to receive approval from the US Food and Drug Administration (FDA). Manufactured by Sandoz, a subsidiary of Novartis, Zarxio is biosimilar to Amgen’s Neupogen (filgrastim), a myeloid growth factor. Zarxio was approved by the European Union in 2009, under the name Zarzio, and its transatlantic approval is for the same indications as Neupogen. Amgen has initiated legal proceedings; its request for a temporary injunction will be heard on March 13, 2015. Peter Johnson (Southampton University, Southampton, UK) welcomes the FDA’s decision. “It could mean fewer regulatory hurdles for new biological drugs to reach the market, avoid needless reduplication of clinical trials, increase competition and drive down costs”, he explains. The approval came www.thelancet.com/oncology Vol 16 April 2015
under an expedited licensing process, during which biosimilar drug trials are not expected to provide a full complement of preclinical and clinical data; the regulator can use evidence from the reference product (in this case Neupogen) to guide its decision. Johnson notes that questions remain over how similar a drug must be to qualify for this process and the circumstances under which new clinical trials would be required. “NICE have some existing guidance on appraising biosimilar drugs, but this principle has yet to be put to the test here in the UK”, adds Johnson. The crucial point is that similar does not mean identical. “The goal is to have biosimilars that reach the market place reasonably quickly”, explains Gary Lyman Lyman (University of Washington, Seattle, WA, USA). “The challenge is establishing a level of safety and efficacy with which
clinicians are comfortable.” Postmarket monitoring will be important to capture any delayed or uncommon adverse events. The market itself will be largely shaped by the response of private insurers and Medicare to the advent of biosimilar drugs. Express Scripts, a US pharmacybenefit management organisation, estimates that introduction of Zarxio could reduce US drugs costs by around US$5·7 billion in the next 10 years. If 11 other biosimilar drugs in development enter the American market, Express Scripts estimates a further $250 billion could be saved. Lyman is optimistic: “my guess is that within 5 years, we’ll have a broader acceptance of biosimilars, they’ll be regularly used in the USA, and healthcare costs will be brought down”, he concludes.
Chassenet/Bsip/Science Photo Library
First biosimilar drug approved in the USA
Published Online March 13, 2015 http://dx.doi.org/10.1016/ S1470-2045(15)70088-4 For the press release by US Food and Drug Administration see http://www.fda.gov/ NewsEvents/Newsroom/ PressAnnouncements/ ucm436648.htm
Talha Khan Burki e161
