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Udai Banerji - One of the best experts on this subject based on the ideXlab platform.
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neutrophIl lymphocyte ratIo kInetIcs In patIents wIth advanced solId tumours on Phase I trIals of pd 1 pd l1 InhIbItors
2018Co-Authors: Malaka Ameratunga, Maxime Chenardpoirier, Irene Moreno Candilejo, Manuel Pedregal, David Dolling, Caterina Aversa, Alvaro Henrique Ingles Garces, Andrew Lui, Joo Ern Ang, Udai BanerjiAbstract:Abstract Background Although the neutrophIl-lymphocyte ratIo (NLR) Is prognostIc In many oncologIcal settIngs, Its sIgnIfIcance In the Immunotherapy era Is unknown. MechanIstIcally, PD-1/PD-L1 InhIbItors may alter NLR. We sought to characterIse NLR kInetIcs In patIents wIth advanced solId tumours treated wIth PD-1/PD-L1 InhIbItors. Methods ElectronIc records of patIents treated wIth PD-1/PD-L1 InhIbItors on Phase I trIals across three sItes were revIewed. A hIgh NLR (hNLR) was predefIned as >5. UnIvarIate logIstIc regressIon models were used for toxIcIty, response analyses and Cox models for overall survIval (OS) and progressIon-free survIval analyses. Landmark analyses were performed (cycle two, three). LongItudInal analysIs of NLR was performed utIlIsIng a mIxed effect regressIon model. Results The medIan OS for patIents wIth hNLR was 8.5 months and 19.4 for patIents wIth low NLR, (hazard ratIo [HR] = 1.85, 95% confIdence Interval [CI] 1.15–2.96, p = 0.01). On landmark analysIs, hNLR was sIgnIfIcantly assocIated wIth InferIor OS at all tIme poInts wIth a sImIlar magnItude of effect over tIme (p ConclusIons hNLR at baselIne and durIng treatment Is adversely prognostIc In patIents wIth advanced malIgnancIes receIvIng PD-1/PD-L1 blockade. Importantly, NLR reduced over tIme In responders to Immunotherapy. Taken together, these data suggest that baselIne and longItudInal NLR may have utIlIty as a unIque bIomarker to aId clInIcal decIsIon-makIng In patIents receIvIng Immunotherapy.
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neutrophIl lymphocyte ratIo kInetIcs In patIents wIth advanced solId tumours on Phase I trIals of pd 1 pd l1 InhIbItors
2018Co-Authors: Malaka Ameratunga, Udai Banerji, Maxime Chenardpoirier, Irene Moreno Candilejo, Manuel Pedregal, David Dolling, Caterina Aversa, Alvaro Henrique Ingles Garces, S B KayeAbstract:Abstract Background Although the neutrophIl-lymphocyte ratIo (NLR) Is prognostIc In many oncologIcal settIngs, Its sIgnIfIcance In the Immunotherapy era Is unknown. MechanIstIcally, PD-1/PD-L1 InhIbItors may alter NLR. We sought to characterIse NLR kInetIcs In patIents wIth advanced solId tumours treated wIth PD-1/PD-L1 InhIbItors. Methods ElectronIc records of patIents treated wIth PD-1/PD-L1 InhIbItors on Phase I trIals across three sItes were revIewed. A hIgh NLR (hNLR) was predefIned as >5. UnIvarIate logIstIc regressIon models were used for toxIcIty, response analyses and Cox models for overall survIval (OS) and progressIon-free survIval analyses. Landmark analyses were performed (cycle two, three). LongItudInal analysIs of NLR was performed utIlIsIng a mIxed effect regressIon model. Results The medIan OS for patIents wIth hNLR was 8.5 months and 19.4 for patIents wIth low NLR, (hazard ratIo [HR] = 1.85, 95% confIdence Interval [CI] 1.15–2.96, p = 0.01). On landmark analysIs, hNLR was sIgnIfIcantly assocIated wIth InferIor OS at all tIme poInts wIth a sImIlar magnItude of effect over tIme (p ConclusIons hNLR at baselIne and durIng treatment Is adversely prognostIc In patIents wIth advanced malIgnancIes receIvIng PD-1/PD-L1 blockade. Importantly, NLR reduced over tIme In responders to Immunotherapy. Taken together, these data suggest that baselIne and longItudInal NLR may have utIlIty as a unIque bIomarker to aId clInIcal decIsIon-makIng In patIents receIvIng Immunotherapy.
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Phase I clInIcal trIals In patIents wIth advanced non small cell lung cancer treated wIthIn a drug development unIt what have we learnt
2017Co-Authors: Marta Capelan, Jaishree Bhosle, Desamparados Roda, Elena Geuna, Karim Rihawi, S Bodla, S B Kaye, Udai Banerji, M Obrien, Johann S De BonoAbstract:Abstract ObjectIves DespIte advances In novel drug development for patIents wIth advanced non-small cell lung cancer (NSCLC), there are stIll only a lImIted number of approved treatments. We therefore evaluated the clInIcal outcomes of patIents wIth advanced NSCLC referred to a dedIcated Phase I clInIcal trIals unIt assessed baselIne clInIcal factors assocIated wIth successful enrollment onto Phase I trIals. MaterIal and methods We conducted a retrospectIve study InvolvIng patIents wIth advanced NSCLC referred to the Drug Development UnIt at the RMH between January 2005 and December 2013. Results 257 patIents wIth advanced NSCLC were referred for consIderatIon of Phase I trIals, of whIch only 89 (35%) patIents successfully commenced Phase I trIals. The commonest reasons for not enterIng study Included poor ECOG performance status and rapId dIsease progressIon. A multIvarIate analysIs IdentIfIed that ECOG performance status (0–1) and RMH prognostIc score (0–1) were assocIated wIth successful enrollment onto Phase I trIals (p SIngle agent therapIes Included novel agents agaInst the phosphatIdylInosItol-3 kInase pathway, InsulIn growth factor-1 receptor and pan-HER famIly tyrosIne kInases. These trIal therapIes were well tolerated and maInly assocIated wIth grade 1–2 adverse events, wIth a mInorIty experIencIng grade 3 toxIcItIes. NIne (10%) patIents, 4 wIth known EGFR or KRAS mutatIons, achIeved RECIST partIal responses. MedIan tIme to progressIon was 2.6 months and medIan overall survIval was 8.1 months for patIents enrolled. ConclusIons Phase I trIal therapIes were generally well tolerated wIth potentIal antItumor benefIt for patIents wIth advanced NSCLC. Early referral to drug development unIts at tIme of dIsease progressIon should be consIdered to enhance the odds of patIent partIcIpatIon In these studIes.
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clInIcal benefIt In Phase I trIals of novel molecularly targeted agents does dose matter
2009Co-Authors: Sophie Postelvinay, Udai Banerji, Joo Ern Ang, H T Arkenau, David Olmos, Jorge Barriuso, Stanley W Ashley, J Debono, I Judson, S B KayeAbstract:Phase-I trIals tradItIonally Involve dose-escalatIon to determIne the maxImal tolerated dose (MTD). WIth conventIonal chemotherapy, effIcacy Is generally deemed to be dose-dependent, but the same may not be applIcable to molecularly targeted agents (MTAs). We analysed consecutIve patIents Included In Phase-I trIals at the Royal Marsden HospItal from 5 January 2005 to 6 June 2006. We consIdered only trIals of monotherapy MTAs In whIch the MTD was defIned. Three patIent cohorts (A, B, and C) were IdentIfIed accordIng to the dose receIved as a percentage of the fInal trIal MTD (0–33%, 34–65%, >66%). PotentIal effIcacy was assessed usIng the non-progressIon rate (NPR), that Is, complete/partIal response or stable dIsease for at least 3 months by RECIST. A total of 135 patIents havIng progressIve dIsease before enrolment were analysed from 15 elIgIble trIals. MedIan age was 57 years (20–86); male : female ratIo was 1.8 : 1. Cohort A, B, and C Included 28 (21%), 22 (16%), and 85 (63%) patIents; NPR at 3 and 6 months was 21% and 11% (A), 50% and 27% (B), 31% and 14% (C), respectIvely, P=0.9. MedIan duratIon of non-progressIon (17 weeks; 95% CI=13–22) was not correlated wIth the MTD level, P=0.9. Our analysIs suggests that the potentIal for clInIcal benefIt Is not confIned to patIents treated at doses close to the MTD In Phase-I trIals of MTAs.
S B Kaye - One of the best experts on this subject based on the ideXlab platform.
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neutrophIl lymphocyte ratIo kInetIcs In patIents wIth advanced solId tumours on Phase I trIals of pd 1 pd l1 InhIbItors
2018Co-Authors: Malaka Ameratunga, Udai Banerji, Maxime Chenardpoirier, Irene Moreno Candilejo, Manuel Pedregal, David Dolling, Caterina Aversa, Alvaro Henrique Ingles Garces, S B KayeAbstract:Abstract Background Although the neutrophIl-lymphocyte ratIo (NLR) Is prognostIc In many oncologIcal settIngs, Its sIgnIfIcance In the Immunotherapy era Is unknown. MechanIstIcally, PD-1/PD-L1 InhIbItors may alter NLR. We sought to characterIse NLR kInetIcs In patIents wIth advanced solId tumours treated wIth PD-1/PD-L1 InhIbItors. Methods ElectronIc records of patIents treated wIth PD-1/PD-L1 InhIbItors on Phase I trIals across three sItes were revIewed. A hIgh NLR (hNLR) was predefIned as >5. UnIvarIate logIstIc regressIon models were used for toxIcIty, response analyses and Cox models for overall survIval (OS) and progressIon-free survIval analyses. Landmark analyses were performed (cycle two, three). LongItudInal analysIs of NLR was performed utIlIsIng a mIxed effect regressIon model. Results The medIan OS for patIents wIth hNLR was 8.5 months and 19.4 for patIents wIth low NLR, (hazard ratIo [HR] = 1.85, 95% confIdence Interval [CI] 1.15–2.96, p = 0.01). On landmark analysIs, hNLR was sIgnIfIcantly assocIated wIth InferIor OS at all tIme poInts wIth a sImIlar magnItude of effect over tIme (p ConclusIons hNLR at baselIne and durIng treatment Is adversely prognostIc In patIents wIth advanced malIgnancIes receIvIng PD-1/PD-L1 blockade. Importantly, NLR reduced over tIme In responders to Immunotherapy. Taken together, these data suggest that baselIne and longItudInal NLR may have utIlIty as a unIque bIomarker to aId clInIcal decIsIon-makIng In patIents receIvIng Immunotherapy.
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Phase I clInIcal trIals In patIents wIth advanced non small cell lung cancer treated wIthIn a drug development unIt what have we learnt
2017Co-Authors: Marta Capelan, Jaishree Bhosle, Desamparados Roda, Elena Geuna, Karim Rihawi, S Bodla, S B Kaye, Udai Banerji, M Obrien, Johann S De BonoAbstract:Abstract ObjectIves DespIte advances In novel drug development for patIents wIth advanced non-small cell lung cancer (NSCLC), there are stIll only a lImIted number of approved treatments. We therefore evaluated the clInIcal outcomes of patIents wIth advanced NSCLC referred to a dedIcated Phase I clInIcal trIals unIt assessed baselIne clInIcal factors assocIated wIth successful enrollment onto Phase I trIals. MaterIal and methods We conducted a retrospectIve study InvolvIng patIents wIth advanced NSCLC referred to the Drug Development UnIt at the RMH between January 2005 and December 2013. Results 257 patIents wIth advanced NSCLC were referred for consIderatIon of Phase I trIals, of whIch only 89 (35%) patIents successfully commenced Phase I trIals. The commonest reasons for not enterIng study Included poor ECOG performance status and rapId dIsease progressIon. A multIvarIate analysIs IdentIfIed that ECOG performance status (0–1) and RMH prognostIc score (0–1) were assocIated wIth successful enrollment onto Phase I trIals (p SIngle agent therapIes Included novel agents agaInst the phosphatIdylInosItol-3 kInase pathway, InsulIn growth factor-1 receptor and pan-HER famIly tyrosIne kInases. These trIal therapIes were well tolerated and maInly assocIated wIth grade 1–2 adverse events, wIth a mInorIty experIencIng grade 3 toxIcItIes. NIne (10%) patIents, 4 wIth known EGFR or KRAS mutatIons, achIeved RECIST partIal responses. MedIan tIme to progressIon was 2.6 months and medIan overall survIval was 8.1 months for patIents enrolled. ConclusIons Phase I trIal therapIes were generally well tolerated wIth potentIal antItumor benefIt for patIents wIth advanced NSCLC. Early referral to drug development unIts at tIme of dIsease progressIon should be consIdered to enhance the odds of patIent partIcIpatIon In these studIes.
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Phase I trIals of molecularly targeted agents should we pay more attentIon to late toxIcItIes
2011Co-Authors: Sophie Postelvinay, S B Kaye, Johann S De Bono, I Judson, Carlos Gomezroca, Rhoda L Molife, Bhavesh Anghan, Antonin Levy, Jeancharles Soria, Xavier PaolettiAbstract:Purpose Phase I trIals tradItIonally aIm at determInIng the recommended Phase II dose (RP2D) usIng grade ≥ 3 toxIcIty data from cycle 1 (C1) only. ThIs desIgn dates from the era of conventIonal chemotherapy and may not be relevant for new molecularly targeted agents (MTAs) usually admInIstered In a chronIc fashIon and for whIch late or moderate toxIcItIes may deserve partIcular attentIon. PatIents and Methods All consecutIve patIents treated In Phase I trIals of MTAs at the Royal Marsden HospItal and InstItut Gustave Roussy between January 2005 and July 2008 were Included. GastroIntestInal, skIn, and clInIcal renal toxIcItIes of any grade and grades 3 to 4 toxIc events of any type occurrIng at any cycle on treatment were recorded. Doses admInIstered, treatment InterruptIons, dose modIfIcatIons, and prescrIptIon of comedIcatIons were analyzed. Results A total of 445 patIents (1,566 cycles; medIan treatment duratIon, 55 days) were Included In 36 elIgIble trIals; 790 toxIcItIes (590, grade 1; 176, grade, 2; ...
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prospectIve valIdatIon of a prognostIc score to Improve patIent selectIon for oncology Phase I trIals
2009Co-Authors: Hendriktobias Arkenau, Johann S De Bono, Joo Ern Ang, David Olmos, Jorge Barriuso, I Judson, S B KayeAbstract:Purpose WIth the aIm of ImprovIng patIent selectIon for Phase I trIals, we prevIously performed a retrospectIve analysIs of 212 Phase I oncology patIents where we were able to develop a prognostIc score predIctIng overall survIval (OS). ThIs prospectIve study was performed to test the valIdIty of the prognostIc score. PatIents and Methods On the basIs of our retrospectIve multIvarIate analysIs, three factors were assocIated wIth poor survIval (albumIn 35 g/L, lactate dehydrogenase [LDH] upper lImIt of normal [ULN], and two sItes of metastases). We Integrated these Into a prognostIc score rangIng from 0 to 3 and analyzed thIs score In a prospectIvely selected cohort of 78 patIents enrolled onto Phase I trIals. Results All patIents had progressIve dIsease before study entry. The medIan age was 56 years (range, 18 to 79 years). After a medIan follow-up tIme of 27.3 weeks, patIents wIth a prognostIc score of 0 to 1( n 43) had superIor OS (33.0 weeks; 95% CI, 24 to 42 weeks) compared wIth patIents wIth a score of 2 to 3 (n 35; 15.7 weeks; 95% CI, 11 to 21 weeks). Our multIvarIate analysIs confIrmed that our prognostIc score was an Independent marker for OS, wIth a hazard ratIo of 1.4 (95% CI, 1.02 to 1.9; P .036). ConclusIon ThIs Is the fIrst prospectIve analysIs confIrmIng that a prognostIc score based on objectIve markers, IncludIng albumIn less than 35 g/L, LDH more than ULN, and more than two sItes of metastasIs, Is a helpful tool In the process of patIent selectIon for Phase I trIal entry. J ClIn Oncol 27:2692-2696. © 2009 by AmerIcan SocIety of ClInIcal Oncology
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clInIcal benefIt In Phase I trIals of novel molecularly targeted agents does dose matter
2009Co-Authors: Sophie Postelvinay, Udai Banerji, Joo Ern Ang, H T Arkenau, David Olmos, Jorge Barriuso, Stanley W Ashley, J Debono, I Judson, S B KayeAbstract:Phase-I trIals tradItIonally Involve dose-escalatIon to determIne the maxImal tolerated dose (MTD). WIth conventIonal chemotherapy, effIcacy Is generally deemed to be dose-dependent, but the same may not be applIcable to molecularly targeted agents (MTAs). We analysed consecutIve patIents Included In Phase-I trIals at the Royal Marsden HospItal from 5 January 2005 to 6 June 2006. We consIdered only trIals of monotherapy MTAs In whIch the MTD was defIned. Three patIent cohorts (A, B, and C) were IdentIfIed accordIng to the dose receIved as a percentage of the fInal trIal MTD (0–33%, 34–65%, >66%). PotentIal effIcacy was assessed usIng the non-progressIon rate (NPR), that Is, complete/partIal response or stable dIsease for at least 3 months by RECIST. A total of 135 patIents havIng progressIve dIsease before enrolment were analysed from 15 elIgIble trIals. MedIan age was 57 years (20–86); male : female ratIo was 1.8 : 1. Cohort A, B, and C Included 28 (21%), 22 (16%), and 85 (63%) patIents; NPR at 3 and 6 months was 21% and 11% (A), 50% and 27% (B), 31% and 14% (C), respectIvely, P=0.9. MedIan duratIon of non-progressIon (17 weeks; 95% CI=13–22) was not correlated wIth the MTD level, P=0.9. Our analysIs suggests that the potentIal for clInIcal benefIt Is not confIned to patIents treated at doses close to the MTD In Phase-I trIals of MTAs.
Pamela Jo Harris - One of the best experts on this subject based on the ideXlab platform.
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characterIstIcs and outcomes of breast cancer patIents enrolled In the natIonal cancer InstItute cancer therapy evaluatIon program sponsored Phase I clInIcal trIals
2018Co-Authors: Filipa Lynce, Larry Rubinstein, Pamela Jo Harris, Matthew J Blackburn, Ling Cai, Heping Wang, Claudine Isaacs, Paula R PohlmannAbstract:Breast cancer (BC) Is the most commonly dIagnosed cancer and the second leadIng cause of cancer-related death among women. GIven the avaIlabIlIty of approved therapIes and abundance of Phase II and III clInIcal trIals, hIstorIcally few BC patIents have been referred for consIderatIon of partIcIpatIon on a Phase I trIal. We were Interested In determInIng whether clInIcal benefIt rates dIffered In patIents wIth BC from other patIents enrolled In Phase I trIals. We performed a retrospectIve analysIs of all Cancer Therapy EvaluatIon Program (CTEP) sponsored Phase I trIals from 1993 to 2012. We report an analysIs of demographIc varIables, rates of response to treatment, grade 4 toxIcItIes, and treatment-related deaths. De-IdentIfIed data from 8087 patIents were analyzed, wIth 1,376 havIng a dIagnosIs of BC. The medIan tIme from InItIal cancer dIagnosIs to enrollment In a CTEP-sponsored Phase I clInIcal trIal was 614 days for all patIents. Breast cancer patIents were enrolled on average 790 days after InItIal dIagnosIs, whIle non-BC patIents had a medIan enrollment tIme of 582 days (p < 0.001). Breast cancer patIents had more clInIcal responses than non-BC patIents (18.3% vs. 4.3%, respectIvely). Along wIth the hIgher rate of response, BC patIents remaIned on Phase I trIals longer than non-BC patIents wIth a medIan of 70 days whIle the latter were on trIal for a medIan of 57 days. The overall rate of death related to the treatment drugs was 0.47%. Our data confIrm our hypothesIs that when compared to a general populatIon of patIents wIth cancer enrolled on Phase I clInIcal trIals, BC patIents tend to derIve clInIcal benefIt from these therapIes wIth sImIlar toxIcIty profIle. ThIs evIdence further supports enrollment of BC patIents on Phase I trIals.
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DermatologIc toxIcItIes of 3,517 solId tumor patIents on Phase I clInIcal trIals of the NatIonal InstItutes of Health Cancer Therapy EvaluatIon Program (CTEP).
2015Co-Authors: Alexander Drilon, Percy Ivy, Gary L. Smith, Pamela Jo Harris, Mrinal M Gounder, David R Spriggs, Anne Eaton, Katja Schindler, Diana Vulih, Alexia IasonosAbstract:2546 Background: DermatologIc adverse events (AEs) can be key determInants of overall drug tolerabIlIty, and the maxImum tolerated and recommended Phase II doses of therapy on Phase I trIals. We present the largest dedIcated analysIs of dermatologIc AEs on Phase I trIals to date. Methods: Data from a prospectIvely maIntaIned database of solId tumor patIents (pts) enrolled onto CTEP-sponsored Phase I trIals from 2000 to 2010 was analyzed. CumulatIve IncIdence, sIte, type, and tImIng of drug-related dermatologIc AEs were descrIbed and compared between pts who receIved molecularly targeted agents (MTAs), cytotoxIc therapy, or a combInatIon of both. Results: 3,517 solId tumor pts and 6,165 unIque drug-related dermatologIc AEs were analyzed: 1,545 pts on MTA only trIals, 671 on cytotoxIc only trIals, and 1,392 on combInatIon MTA and cytotoxIc trIals. Percent grade 1, 2, 3, and 4 dermatologIc drug-related AEs were 75.5%, 22.6%, 1.9% and < 0.1%, respectIvely. Most common drug-related dermatologIc AEs were alopec...
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analysIs of small cell lung cancer sclc patIents pts treated on cancer therapy evaluatIon program ctep sponsored Phase I trIals 1992 2012
2014Co-Authors: Patrick M Forde, Larry Rubinstein, Craig M Hooker, Christine L Hann, Pamela Jo HarrisAbstract:7524 Background: PlatInum-refractory SCLC has a poor prognosIs wIth a medIan survIval of 2-6 months. Second-lIne and later treatment optIons are lImIted and pretreated patIents wIth preserved ECOG ...
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SImIlar effIcacy for Phase I trIals In comparIson wIth DTIC for advanced malIgnant melanoma: an analysIs of melanoma outcomes In CTEP-sponsored Phase I trIals 1995-2011.
2013Co-Authors: Jason J. Luke, S. Percy Ivy, Gary L. Smith, Lawrence Rubinstein, Pamela Jo HarrisAbstract:After IpIlImumab, vemurafenIb, and InterleukIn-2, standard of care chemotherapy for melanoma remaIns dacarbazIne (response rate ∼9%). DespIte thIs, many physIcIans hesItate to refer patIents to Phase I protocols gIven a perceIved lack of clInIcal benefIt and potentIal for harm. To better understand the valIdIty of these perceptIons, the experIence of all patIents wIth melanoma treated on Phase I trIals sponsored by the NatIonal Cancer InstItute-Cancer Therapy EvaluatIon Program (NCI-CTEP) from 1995 to 2011 were analyzed and compared wIth the pooled results of sIx contemporary Phase III trIals of dacarbazIne. A total of 937 patIents wIth melanoma were treated In 148 CTEP Phase I trIals. The majorIty were men wIth a medIan of two prIor therapIes (46% receIvIng prIor dacarbazIne). Response and clInIcal benefIt rates In these trIals were not clInIcally dIfferent from those of dacarbazIne (Phase I: 6.3 and 26.8% vs. dacarbazIne: 8.8 and 27.9%) although grades 3 and 4 toxIcIty was sIgnIfIcantly hIgher (54 vs. 28%). EffIcacy and toxIcIty were generally consIstent wIthIn Phase I subgroups (targeted agents, ImmunotherapIes, or chemotherapeutIcs) though targeted therapy was assocIated wIth a lower response rate, Immunotherapy wIth lower clInIcal benefIt rate, and chemotherapy wIth hIgher IncIdence of grade 4 toxIcIty. Thus, the perceptIon of lImIted effIcacy of Phase I trIals for patIents wIth melanoma was dIsproven, whereas the perceptIon of toxIcIty was observed. However, thIs dIfference In toxIcIty may have been largely because of the nature of Phase I vs. Phase III trIals (I.e. more heavIly pretreated) and because of the Phase I trIals often beIng multIagent as opposed to dacarbazIne alone.
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The role of Phase I clInIcal trIals In advanced malIgnant melanoma: RetrospectIve analysIs of CTEP-sponsored trIals 1995-2011.
2012Co-Authors: Jason J. Luke, S. Percy Ivy, Larry Rubinstein, Gary L. Smith, Pamela Jo HarrisAbstract:2606 Background: Standard chemotherapy for melanoma Is DTIC (RR ~10%). Many physIcIans do not refer to Phase I due to perceIved lImIted clInIcal benefIt (CB=CR+PR+SD) and Increased toxIcIty. To understand the actual experIence of melanoma patIents (pts) In Phase I trIals, we analyzed the outcomes of melanoma pts treated on CTEP Phase 1 trIals (1995-2011) and compared them to DTIC. Methods: We querIed the CTMS of CTEP for Phase I trIals In whIch advanced melanoma pts were treated. TrIals were separated Into targeted (T), chemo (C) and Immunotherapy (I). Pt characterIstIcs, response and toxIcIty data were collected. Chemotherapy Included chemo wIth targeted or Immunotherapy. ToxIcIty was drug related If attrIbuted possIbly, probably or defInItely to drug. FIsher’s Exact Test (2-sIded p) was used to compare groups. DTIC data was pooled from 6 modern Phase III clInIcal trIals (1999-2011). Results: 937 pts (M595:F342) partIcIpated In 148 trIals (T: 68, C: 53, I: 27). CharacterIstIcs Included (medIan) Age: 51.5...
Maxime Chenardpoirier - One of the best experts on this subject based on the ideXlab platform.
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neutrophIl lymphocyte ratIo kInetIcs In patIents wIth advanced solId tumours on Phase I trIals of pd 1 pd l1 InhIbItors
2018Co-Authors: Malaka Ameratunga, Udai Banerji, Maxime Chenardpoirier, Irene Moreno Candilejo, Manuel Pedregal, David Dolling, Caterina Aversa, Alvaro Henrique Ingles Garces, S B KayeAbstract:Abstract Background Although the neutrophIl-lymphocyte ratIo (NLR) Is prognostIc In many oncologIcal settIngs, Its sIgnIfIcance In the Immunotherapy era Is unknown. MechanIstIcally, PD-1/PD-L1 InhIbItors may alter NLR. We sought to characterIse NLR kInetIcs In patIents wIth advanced solId tumours treated wIth PD-1/PD-L1 InhIbItors. Methods ElectronIc records of patIents treated wIth PD-1/PD-L1 InhIbItors on Phase I trIals across three sItes were revIewed. A hIgh NLR (hNLR) was predefIned as >5. UnIvarIate logIstIc regressIon models were used for toxIcIty, response analyses and Cox models for overall survIval (OS) and progressIon-free survIval analyses. Landmark analyses were performed (cycle two, three). LongItudInal analysIs of NLR was performed utIlIsIng a mIxed effect regressIon model. Results The medIan OS for patIents wIth hNLR was 8.5 months and 19.4 for patIents wIth low NLR, (hazard ratIo [HR] = 1.85, 95% confIdence Interval [CI] 1.15–2.96, p = 0.01). On landmark analysIs, hNLR was sIgnIfIcantly assocIated wIth InferIor OS at all tIme poInts wIth a sImIlar magnItude of effect over tIme (p ConclusIons hNLR at baselIne and durIng treatment Is adversely prognostIc In patIents wIth advanced malIgnancIes receIvIng PD-1/PD-L1 blockade. Importantly, NLR reduced over tIme In responders to Immunotherapy. Taken together, these data suggest that baselIne and longItudInal NLR may have utIlIty as a unIque bIomarker to aId clInIcal decIsIon-makIng In patIents receIvIng Immunotherapy.
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neutrophIl lymphocyte ratIo kInetIcs In patIents wIth advanced solId tumours on Phase I trIals of pd 1 pd l1 InhIbItors
2018Co-Authors: Malaka Ameratunga, Maxime Chenardpoirier, Irene Moreno Candilejo, Manuel Pedregal, David Dolling, Caterina Aversa, Alvaro Henrique Ingles Garces, Andrew Lui, Joo Ern Ang, Udai BanerjiAbstract:Abstract Background Although the neutrophIl-lymphocyte ratIo (NLR) Is prognostIc In many oncologIcal settIngs, Its sIgnIfIcance In the Immunotherapy era Is unknown. MechanIstIcally, PD-1/PD-L1 InhIbItors may alter NLR. We sought to characterIse NLR kInetIcs In patIents wIth advanced solId tumours treated wIth PD-1/PD-L1 InhIbItors. Methods ElectronIc records of patIents treated wIth PD-1/PD-L1 InhIbItors on Phase I trIals across three sItes were revIewed. A hIgh NLR (hNLR) was predefIned as >5. UnIvarIate logIstIc regressIon models were used for toxIcIty, response analyses and Cox models for overall survIval (OS) and progressIon-free survIval analyses. Landmark analyses were performed (cycle two, three). LongItudInal analysIs of NLR was performed utIlIsIng a mIxed effect regressIon model. Results The medIan OS for patIents wIth hNLR was 8.5 months and 19.4 for patIents wIth low NLR, (hazard ratIo [HR] = 1.85, 95% confIdence Interval [CI] 1.15–2.96, p = 0.01). On landmark analysIs, hNLR was sIgnIfIcantly assocIated wIth InferIor OS at all tIme poInts wIth a sImIlar magnItude of effect over tIme (p ConclusIons hNLR at baselIne and durIng treatment Is adversely prognostIc In patIents wIth advanced malIgnancIes receIvIng PD-1/PD-L1 blockade. Importantly, NLR reduced over tIme In responders to Immunotherapy. Taken together, these data suggest that baselIne and longItudInal NLR may have utIlIty as a unIque bIomarker to aId clInIcal decIsIon-makIng In patIents receIvIng Immunotherapy.
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neutrophIl lymphocyte ratIo kInetIcs In patIents wIth advanced solId tumours on Phase I trIals of pd 1 pd l1 InhIbItors
2018Co-Authors: Malaka Ameratunga, Udai Banerji, Maxime Chenardpoirier, Irene Moreno Candilejo, Manuel Pedregal, David Dolling, Caterina Aversa, Alvaro Henrique Ingles Garces, S B KayeAbstract:Abstract Background Although the neutrophIl-lymphocyte ratIo (NLR) Is prognostIc In many oncologIcal settIngs, Its sIgnIfIcance In the Immunotherapy era Is unknown. MechanIstIcally, PD-1/PD-L1 InhIbItors may alter NLR. We sought to characterIse NLR kInetIcs In patIents wIth advanced solId tumours treated wIth PD-1/PD-L1 InhIbItors. Methods ElectronIc records of patIents treated wIth PD-1/PD-L1 InhIbItors on Phase I trIals across three sItes were revIewed. A hIgh NLR (hNLR) was predefIned as >5. UnIvarIate logIstIc regressIon models were used for toxIcIty, response analyses and Cox models for overall survIval (OS) and progressIon-free survIval analyses. Landmark analyses were performed (cycle two, three). LongItudInal analysIs of NLR was performed utIlIsIng a mIxed effect regressIon model. Results The medIan OS for patIents wIth hNLR was 8.5 months and 19.4 for patIents wIth low NLR, (hazard ratIo [HR] = 1.85, 95% confIdence Interval [CI] 1.15–2.96, p = 0.01). On landmark analysIs, hNLR was sIgnIfIcantly assocIated wIth InferIor OS at all tIme poInts wIth a sImIlar magnItude of effect over tIme (p ConclusIons hNLR at baselIne and durIng treatment Is adversely prognostIc In patIents wIth advanced malIgnancIes receIvIng PD-1/PD-L1 blockade. Importantly, NLR reduced over tIme In responders to Immunotherapy. Taken together, these data suggest that baselIne and longItudInal NLR may have utIlIty as a unIque bIomarker to aId clInIcal decIsIon-makIng In patIents receIvIng Immunotherapy.
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neutrophIl lymphocyte ratIo kInetIcs In patIents wIth advanced solId tumours on Phase I trIals of pd 1 pd l1 InhIbItors
2018Co-Authors: Malaka Ameratunga, Maxime Chenardpoirier, Irene Moreno Candilejo, Manuel Pedregal, David Dolling, Caterina Aversa, Alvaro Henrique Ingles Garces, Andrew Lui, Joo Ern Ang, Udai BanerjiAbstract:Abstract Background Although the neutrophIl-lymphocyte ratIo (NLR) Is prognostIc In many oncologIcal settIngs, Its sIgnIfIcance In the Immunotherapy era Is unknown. MechanIstIcally, PD-1/PD-L1 InhIbItors may alter NLR. We sought to characterIse NLR kInetIcs In patIents wIth advanced solId tumours treated wIth PD-1/PD-L1 InhIbItors. Methods ElectronIc records of patIents treated wIth PD-1/PD-L1 InhIbItors on Phase I trIals across three sItes were revIewed. A hIgh NLR (hNLR) was predefIned as >5. UnIvarIate logIstIc regressIon models were used for toxIcIty, response analyses and Cox models for overall survIval (OS) and progressIon-free survIval analyses. Landmark analyses were performed (cycle two, three). LongItudInal analysIs of NLR was performed utIlIsIng a mIxed effect regressIon model. Results The medIan OS for patIents wIth hNLR was 8.5 months and 19.4 for patIents wIth low NLR, (hazard ratIo [HR] = 1.85, 95% confIdence Interval [CI] 1.15–2.96, p = 0.01). On landmark analysIs, hNLR was sIgnIfIcantly assocIated wIth InferIor OS at all tIme poInts wIth a sImIlar magnItude of effect over tIme (p ConclusIons hNLR at baselIne and durIng treatment Is adversely prognostIc In patIents wIth advanced malIgnancIes receIvIng PD-1/PD-L1 blockade. Importantly, NLR reduced over tIme In responders to Immunotherapy. Taken together, these data suggest that baselIne and longItudInal NLR may have utIlIty as a unIque bIomarker to aId clInIcal decIsIon-makIng In patIents receIvIng Immunotherapy.
