Speaker's Conference Research Articles

1488P - Vemurafenib in patients (pts) harboring BRAF V600 mutation: Results of non-small cell lung cancer (NSCLC) cohort from the AcSé trial

Background: BRAF mutations are found in 2-3% of NSCLC. BRAF inhibitors reportedly have antitumor activity. The French National Cancer Institute (INCa) launched a program giving nationwide access to vemurafenib for cancer pts with BRAF-mutated tumors and supporting molecular screening. We report here the results of the NSCLC cohort. Methods: BRAF mutational status was assessed on INCa molecular genetic centers by direct sequencing or NGS. Pts with BRAF V600E mutation, progressing after ≥1 standard treatment were proposed vemurafenib 960 mg BID. Objective Response Rate (ORR) was assessed using RECIST v1.1 every 8 weeks. A sequential Bayesian approach was planned to allow early stopping using an inefficacy boundary for ORR of 10%. If no early stopping occurred, the treatment was considered worthy for further evaluation if there was a 90% probability that the estimated ORR is ≥ 30%, the efficacy boundary. Results: From 10/2014 to 10/2017, 101 NSCLC pts harboring BRAF V600E were enrolled. Median age: 68 years (range 41–85), 68% smokers, 50% females, 100% non-squamous histology and 19% with ECOG PS 2. Most frequent grade ≥3 adverse events (AEs) were asthenia (10% of pts), epidermoid carcinoma (7%), dermatitis (6%) and increased GGT (6%). Three toxic deaths were reported: 1 nausea and vomiting leading to dehydration, 1 pneumonia and 1 neutropenic sepsis. Among the enrolled pts, 100 BRAF V600E NSCLC pts evaluable for the best overall response (BOR), 43 PR, 21 SD, 16 PD, 12 deaths before assessment and 8 not evaluable (no tumor assessment) were observed. The mean objective response rate was 44.9% (95% CI: 35.2; 54.8), the efficacy boundary was reached with a predictive probability greater than 90%. Median duration of response was 6.5 months (5.1-7.3). Median progression-free survival (PFS) was 5.2 months (3.8-6.9) and median OS was 9.3 months. Nine pts were still on treatment at the cut-off date, 91 have stopped vemurafenib (55 PD, 23 AEs, 3 deaths, 1 doctor’s decision, 9 patient’s decisions). Conclusions: Vemurafenib provided reasonable response rate and prolonged PFS in BRAF V600E pretreated NSCLC. These results confirm the activity of BRAF inhibitors in these pts and underline the need of integrating BRAF V600E in biomarkers routine screening. Clinical trial identification: NCT02304809. Legal entity responsible for the study: UNICANCER. Funding: ARC Foundation French National Cancer Institute (INCa) Roche. Disclosure: J. Mazières: Ad Board, Research grant: Roche, BMS, Astra Zeneca. F. Barlesi: Honoraria: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Clovis Oncology, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, MSD, Pierre Fabre, Pfizer and Takeda. V. Avrillon: Advisory Board: Roche, BMS. G. Ferretti: Speaker conference: Boehringer, Roche, GEMS. J.Y. Blay: Advisory Board: Roche, Lilly, Ignyta, Deciphera, Novartis, Bayer, BMS; Corporate-sponsored Research: Roche, Lilly, Ignyta, Deciphera, Novartis, Bayer, Novartis, GSK, AstraZeneca, MSD; Other Substantive Relationships: Surveillance committee of Innate Pharma. All other authors have declared no conflicts of interest.

Devolution and Parliamentary Representation: The Case of the Scotland and Wales Bill, 1976–7

AbstractFor as long as devolution has been debated in the UK, there has been fierce discussion as to the representation of the would‐be affected areas at Westminster. That this has been the case is a consequence of Westminster's dual remit as both a state‐wide and a sub‐state legislature. While this dual remit was relatively straightforward when applied to all nations of the UK, it does, however, raise serious questions about the equality of MPs at Westminster in the face of asymmetric devolution that would carve out parliament's remit in some, but not all, parts of the UK. These questions bedevilled Gladstone's Irish Home Rule Bills in the late 19th century and have been a recurrent feature of debate following New Labour's devolution programme in the late 1990s, culminating in the adoption of a system of ‘English Votes for English Laws’ by the house of commons in October 2015. This article looks at this issue through the lens of the ill‐fated Scotland and Wales Bill introduced by the Callaghan government in 1976. It explores the roots of the bill and how, and why, the idea of referring the question of territorial representation, post‐devolution, to a Speaker's conference, came to secure the initial support of cabinet as the best answer to this problem, and why the government swiftly changed its mind. Parliamentary statecraft considerations served to push a Speaker's conference onto the institutional agenda, before ultimately dooming it to failure.

Women and the Vote: The Parliamentary Path to Equal Franchise, 1918–28

AbstractFollowing the Speaker's conference on electoral reform of 1916–17, the Representation of the People Act 1918 gave women over the age of 30 years who met minimum property qualifications the parliamentary vote for the first time. After a decade of continued suffrage campaigning and pressure in parliament, the Representation of the People (Equal Franchise) Act 1928 gave women the vote on the same terms as men, at age 21 years, with no age or any other restrictions. Although important in itself, votes for women also carried along a wider agenda of legislation relating to gender equality and issues affecting women and children during the interwar period. This essay gives an overview of how the Speaker's conference and the 1918 act affected women, considers the immediately‐related legislation in 1918–19 which allowed women to become MPs and removed other sex disqualifications, and traces progress in parliament towards equal franchise over the next decade, including a pledge by Stanley Baldwin in 1924 and an undertaking by William Joynson‐Hicks in 1925. It explains the changes in personnel and attitudes over time which finally enabled a Conservative government to grant equal franchise in 1928.

The Conservative Party and the Impact of the 1918 Reform Act

AbstractBefore the First World War, the Conservative Party feared the extension of the suffrage to all adult males, and was divided over even a limited granting of votes to women. However, the patriotic public response to the war moderated these attitudes, and by 1916 the Conservatives were in favour of giving the vote to all servicemen. Although the Conservatives were represented in the Speaker's conference which drew up proposals for electoral reform, when its report was published in January 1917, these were almost entirely opposed by the party organisation. However, the Conservatives came to accept adult male suffrage as the only practicable way of recognizing the servicemen's contribution. During the passage of the electoral reform bill, they successfully amended it in several respects and secured gains from the redistribution of constituencies. This essay assesses the Conservative response to the reform proposals and the impact of the Representation of the People Act 1918 upon the party's fortunes, organisation, and culture. During the following decade, the Conservative Party made substantial efforts to reach the female, younger, and working‐class voters. While it was reassured by electoral success, and especially support from women, there remained concerns about the nature of democracy and demands from the grass roots for a defensive restoration of powers to the house of lords. However, by 1928, giving the vote to women on equal terms of adult citizenship was seen as the inevitable completion of the new electoral system – in which the Conservatives became the most successful party.

The Labour Party and the Impact of the 1918 Reform Act

AbstractThe Representation of the People Act 1918 compelled the Labour Party to respond by changing its organisation. Labour was already in the process of changing its organisation, policies and constitution because of the transformed economic, social, and political circumstances of the Great War. Labour took particular care to adjust its organisation to appeal to women voters, especially working‐class ones. It also aimed its electoral appeal to white‐collar workers, male and female. Labour benefited in 1919–20 from the wider local government franchise in London and some other urban areas, but such advances were thereafter countered by the Conservatives and Liberals avoiding dividing the anti‐Labour vote. It is possible that Labour benefited to a small extent in a few inner‐city constituencies by the ending of electoral disqualification for receiving out relief under the poor law. By the 1922 general election, Labour was establishing electoral strongholds in many mining, industrial and inner‐city parliamentary seats. Labour welcomed the changes proposed by the Speaker's conference but, to the dismay of some of its supporters, it accepted the loss of the proportional representation proposals in the compromises made as the Representation of the People Bill went through parliament. In the longer term, the lack of proportional representation enabled Labour to form majority governments in 1945 and later.

Substantive Religious Representation in the UK Parliament: Examining Parliamentary Questions for Written Answers, 1997–2012

The substantive representation of minority groups in national legislatures is a topic of significant normative, theoretical and empirical importance. Addressing this question, this article focuses on what drives Members of the UK House of Commons to raise issues on concern for Jewish and Muslim minority groups in relatively low-cost parliamentary activity, i.e. Parliamentary Questions for written answers (WPQs). Drawing on the suggested positive relationship between descriptive and substantive minority representation (e.g. Hansard (2009), Speaker's Conference (on Parliamentary Representation): Final Report, London, The Stationery Office Limited), it uses content and statistical analysis to examine if having a Jewish or Muslim background impacts on the frequency and the probability of MPs’ engagement with minority issues, and how this effect compares to that from institutional predictors, namely the party parliamentary status and the minority presence in a constituency. The findings demonstrate that a religious minority background has a limited impact on MPs’ engagement with minority issues in WPQs, being inferior to that of institutional predictors. Being in Opposition, in particular, has a consistent, positive influence on the content of WPQs, whereby Opposition MPs table more WPQs on the issues of minority concern than Members from the party of Government.

Back to the Future? Warnings from History for a Future UK Constitutional Convention

AbstractAmid the fallout from the Scottish independence referendum, a UK constitutional convention has been proposed as a mechanism to take stock not only of the referendum, but also of the past fifteen years of devolution. However, despite longstanding conceptions of British constitutional development, a constitutional convention would not herald a brave new world for the UK's constitution. As the article highlights, in the past hundred years there have been two attempts to treat the territorial constitution in the round: the Speaker's Conference on Devolution, 1919–1920 and the Royal Commission on the Constitution, 1969–1973. This article examines both of these forums, arguing that they provide clear warnings for a future UK constitutional convention, in particular the threat of internal division that any such forum risks facing. A danger that this article highlights is heightened by the associated difficulty of reaching agreement across the UK's ‘state of unions’.

Out of the Hands of the Parties: Women's Legislative Recruitment at Westminster

At the next general election the percentage of women elected to the smaller House of Commons risks being lower than in the current parliament, where they constitute 22 percent of all MPs. The 2008–10 Speaker's Conference identified many of the barriers faced by women and other under‐represented groups and made a series of recommendations, only some of which have been introduced. The Government favours a voluntary approach to Recommendation 24, which calls for diversity data monitoring, whilst Recommendation 25 which calls for serious consideration of legislative quotas in the absence of a significant increase in the numbers of women in 2010, appears forgotten. A second Speaker's Conference should therefore be established; the issue of women's under‐representation should be taken up above the party level—with legislative quotas introduced to address the system level failure of democratic representation at Westminster.

A Long Way to Go: The Final Report of the Speaker's Conference on Parliamentary Representation

The Speaker's Conference on Parliamentary Representation reported in January 2010. The report calls for a host of measures to improve the representativeness of the House of Commons and to revitalise political parties, as well as to enhance citizenship education, develop youth and community citizenship engagement programmes, and more generally to revitalise British democracy. Early responses indicate that the government and political parties will take the report seriously. The report is thoughtful, thorough and extensive, a treasure trove for policy makers, advocates and researchers. If it has a weakness, it is that it shows a better understanding of parliamentary reform than of party reform.

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University Representation in Parliament

THE provisions of the Franchise Bill as regards the representation of Universities are based on the recommendations of the Speaker's Con ference on Electoral Reform, issued early in the present year, under which Oxford and Cambridge retain two members each, London is grouped with Durham, Manchester, Birmingham, Liver pool, Leeds, Sheffield, Bristol, and Wales to form a constituency returning three members, and the Scottish Universities are to form a single constitu ency returning three members. The degree is to be the basis for electoral qualification. In view of the attacks to which the University franchise has been subject in recent years, this full recogni tion of the principle of University representation will be gratifying to those who believe that it con stitutes a valuable element in our electoral system. As Mr. Balfour said in the House of Commons in July, 1913, the representation of Universities is an honour paid by, the country to the cause of higher education, which gives the power of getting into the House of Commons men of science, men of scholarship, men of special and peculiar gifts quite alien from the ordinary work ing politician. It is, both in theory and practice, a form of proportional representation, enabling men and women of special training and experience to form themselves into constituencies and to return to Parliament representatives qualified to promote higher education and the advancement of science and learning, aspects of our public life which are least likely to secure representation through the ordinary channels.