Survival benefit with checkpoint inhibitors versus chemotherapy is modified by brain metastases in patients with recurrent small cell lung cancer

IntroductionSmall cell lung cancer (SCLC) is a rapidly growing malignancy with early distant metastases. Up to 70% will develop brain metastases, and the poor prognosis of these patients has not changed considerably. The potential of checkpoint inhibitors (CPI) in treating recurrent (r/r) SCLC and their effect on brain metastases remain unclear.MethodsIn this retrospective multicenter study, we analyzed r/r SCLC patients receiving second or further-line CPI versus chemotherapy between 2010 and 2020. We applied multivariable-adjusted Cox regression analysis to test for differences in 1-year mortality and real-world progression. We then used interaction analysis to evaluate whether brain metastases (BM) and/or cranial radiotherapy (CRT) modified the effect of CPI versus chemotherapy on overall survival.ResultsAmong 285 patients, 99 (35%) received CPI and 186 (65%) patients received chemotherapy. Most patients (93%) in the CPI group received nivolumab/ipilimumab. Chemotherapy patients were entirely CPI-naïve and only one CPI patient had received atezolizumab for first-line treatment. CPI was associated with a lower risk of 1-year mortality (adjusted Hazard Ratio [HRadj] 0.59, 95% CI 0.42 to 0.82, p=0.002). This benefit was modified by BM and CRT, indicating a pronounced effect in patients without BM (with CRT: HRadj 0.34, p=0.003; no CRT: HRadj 0.50, p=0.05), while there was no effect in patients with BM who received CRT (HRadj 0.85, p=0.59).ConclusionCPI was associated with a lower risk of 1-year mortality compared to chemotherapy. However, the effect on OS was significantly modified by intracranial disease and radiotherapy, suggesting the benefit was driven by patients without BM

Policy, Office and Votes: The Electoral Value of Ministerial Office

Parties are not unitary actors, and legislators within the same party may have divergent interests, which complicates the understanding of parties? motivations and behaviour. This article argues that holding a ministerial portfolio confers an electoral advantage, and so, in contrast to their co-partisans, politicians who are ministers simultaneously maximize policy, office and votes. New data on Irish elections over a thirty-year period show that ministers are insulated from the electoral cost of governing compared with their co-partisans. Differentiating between ministers and their co-partisans helps to resolve the puzzle of political parties? choosing to enter government despite the evident electoral costs they will encounter. Moreover, previously overlooked electoral benefits of ministerial office help explain their desirability, and thus their ability to incentivize legislative behaviour in parliamentary regimes

Party System Polarisation and Government Duration in Central and Eastern Europe

Since the transition to democracy in the early 1990s, more than 60 percent of governments in Central and Eastern Europe have terminated prematurely. This article argues that the character of party system development in the region has facilitated the emergence of a polarized pattern of party competition and that competition for government now takes place in distinct ideological blocs. Parties seek to form governments within these blocs but not across them and therefore there is little incentive to defect from a governing coalition due to the lack of viable alternatives. As a result, more polarized party systems produce more durable governments. The empirical evidence shows that polarization and ideological diversity of the government are significant indicators of government duration in Central and Eastern Europe. Ideologically compact governments formed within narrow blocs in the party system survive longer than ideologically diverse coalitions that emerge from less polarized party systems

DataSheet_1_Survival benefit with checkpoint inhibitors versus chemotherapy is modified by brain metastases in patients with recurrent small cell lung cancer.docx

IntroductionSmall cell lung cancer (SCLC) is a rapidly growing malignancy with early distant metastases. Up to 70% will develop brain metastases, and the poor prognosis of these patients has not changed considerably. The potential of checkpoint inhibitors (CPI) in treating recurrent (r/r) SCLC and their effect on brain metastases remain unclear.MethodsIn this retrospective multicenter study, we analyzed r/r SCLC patients receiving second or further-line CPI versus chemotherapy between 2010 and 2020. We applied multivariable-adjusted Cox regression analysis to test for differences in 1-year mortality and real-world progression. We then used interaction analysis to evaluate whether brain metastases (BM) and/or cranial radiotherapy (CRT) modified the effect of CPI versus chemotherapy on overall survival.ResultsAmong 285 patients, 99 (35%) received CPI and 186 (65%) patients received chemotherapy. Most patients (93%) in the CPI group received nivolumab/ipilimumab. Chemotherapy patients were entirely CPI-naïve and only one CPI patient had received atezolizumab for first-line treatment. CPI was associated with a lower risk of 1-year mortality (adjusted Hazard Ratio [HRadj] 0.59, 95% CI 0.42 to 0.82, p=0.002). This benefit was modified by BM and CRT, indicating a pronounced effect in patients without BM (with CRT: HRadj 0.34, p=0.003; no CRT: HRadj 0.50, p=0.05), while there was no effect in patients with BM who received CRT (HRadj 0.85, p=0.59).ConclusionCPI was associated with a lower risk of 1-year mortality compared to chemotherapy. However, the effect on OS was significantly modified by intracranial disease and radiotherapy, suggesting the benefit was driven by patients without BM.</p