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2. Prognostic gene expression signature for high-grade serous ovarian cancer

Author

Millstein, J, Budden, T, Goode, EL, Anglesio, MS, Talhouk, A, Intermaggio, MP, Leong, HS, Chen, S, Elatre, W, Gilks, B, Nazeran, T, Volchek, M, Bentley, RC, Wang, C, Chiu, DS, Kommoss, S, Leung, SCY, Senz, J, Lum, A, Chow, V, Sudderuddin, H, Mackenzie, R, George, J, Group, AOCS, Bowtell, D, Chenevix-Trench, G, Green, A, Webb, P, DeFazio, A, Gertig, D, Traficante, N, Fereday, S, Moore, S, Hung, J, Harrap, K, Sadkowsky, T, Pandeya, N, Malt, M, Mellon, A, Robertson, R, Bergh, T Vanden, Jones, M, Mackenzie, P, Maidens, J, Nattress, K, Chiew, YE, Stenlake, A, Sullivan, H, Alexander, B, Ashover, P, Brown, S, Corrish, T, Green, L, Jackman, L, Ferguson, K, Martin, K, Martyn, A, Ranieri, B, White, J, Jayde, V, Mamers, P, Bowes, L, Galletta, L, Giles, D, Hendley, J, Alsop, K, Schmidt, T, Shirley, H, Ball, C, Young, C, Viduka, S, Tran, Hoa, Bilic, Sanela, Glavinas, Lydia, Brooks, Julia, Stuart-Harris, R, Kirsten, F, Rutovitz, J, Clingan, P, Glasgow, A, Proietto, A, Braye, S, Otton, G, Shannon, J, Bonaventura, T, Stewart, J, Begbie, S, Friedlander, M, Bell, D, Baron-Hay, S, Ferrier, AA, Gard, G, Nevell, D, Pavlakis, N, Valmadre, S, Young, B, Camaris, C, Crouch, R, Edwards, L, and Hacker, N

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetic Testing, Genetics, Cancer, Ovarian Cancer, Rare Diseases, 4.2 Evaluation of markers and technologies, 4.4 Population screening, Detection, screening and diagnosis, Cystadenocarcinoma, Serous, Female, Humans, Ovarian Neoplasms, Prognosis, Proportional Hazards Models, Survival Analysis, Transcriptome, formalin-fixed paraffin-embedded, gene expression, high-grade serous ovarian cancer, overall survival, prognosis, AOCS Group, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
Abstract

BackgroundMedian overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ∼4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC.Patients and methodsExpression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, was measured using NanoString technology from formalin-fixed paraffin-embedded tumour tissue collected from 3769 women with HGSOC from multiple studies. Elastic net regularization for survival analysis was applied to develop a prognostic model for 5-year OS, trained on 2702 tumours from 15 studies and evaluated on an independent set of 1067 tumours from six studies.ResultsExpression levels of 276 genes were associated with OS (false discovery rate < 0.05) in covariate-adjusted single-gene analyses. The top five genes were TAP1, ZFHX4, CXCL9, FBN1 and PTGER3 (P < 0.001). The best performing prognostic signature included 101 genes enriched in pathways with treatment implications. Each gain of one standard deviation in the gene expression score conferred a greater than twofold increase in risk of death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 2.02-2.71; P < 0.001]. Median survival [HR (95% CI)] by gene expression score quintile was 9.5 (8.3 to -), 5.4 (4.6-7.0), 3.8 (3.3-4.6), 3.2 (2.9-3.7) and 2.3 (2.1-2.6) years.ConclusionThe OTTA-SPOT (Ovarian Tumor Tissue Analysis consortium - Stratified Prognosis of Ovarian Tumours) gene expression signature may improve risk stratification in clinical trials by identifying patients who are least likely to achieve 5-year survival. The identified novel genes associated with the outcome may also yield opportunities for the development of targeted therapeutic approaches.

Published
2020

5. An Update on Emerging Therapeutic Options for Malignant Pleural Mesothelioma

Author

Davis A, Ke H, Kao S, and Pavlakis N

Subjects
immune checkpoint inhibitors, immunotherapy, malignant pleura mesothelioma, mesothelioma radiotherapy, mesothelioma surgery, trimodality therapy., Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Alexander Davis,1,2 Helen Ke,3 Steven Kao,1,3,4 Nick Pavlakis4– 6 1Department of Medical Oncology, Chris O’Brien Lifehouse, Camperdown, NSW, Australia; 2Department of Medical Oncology, Western Cancer Centre, Dubbo, NSW, Australia; 3Asbestos Diseases Research Institute, Rhodes, NSW, Australia; 4School of Medicine, University of Sydney, Camperdown, NSW, Australia; 5Department of Medical Oncology, Royal North Shore Hospital, St Leonards, NSW, Australia; 6Department of Medical Oncology, Genesis Care, St Leonards, NSW, AustraliaCorrespondence: Nick Pavlakis, Department of Medical Oncology, Royal North Shore Hospital, St Leonards, NSW, 2065, Australia, Tel +612 9463 1172, Fax +612 9463 1092, Email nick.pavlakis@sydney.edu.auAbstract: The treatment paradigm for malignant pleural mesothelioma (MPM) has changed little in the last 18 years. Radical intent treatment, consisting of surgical resection, radiotherapy and chemotherapy, has been offered to a highly select few; however, there is little randomised evidence to validate this approach. Prior to 2020 chemotherapy with platinum and an anti-folate was the only intervention with randomised evidence to demonstrate improved overall survival (OS) in MPM. No systemic therapy had been demonstrated to improve OS in the second line setting until 2020. The publication of the Checkmate 743 trial in 2021 demonstrated a survival benefit of combination immunotherapy over standard chemotherapy in newly diagnosed patients with MPM. This finding was shortly followed by the CONFIRM trial which demonstrates a modest but significant survival benefit of second line nivolumab versus placebo in patients having previously received standard chemotherapy. The results of these trials, recent biomarker directed therapy and chemotherapy adjuncts are discussed within this review. The integration of immunotherapy for the few patients in whom radical surgical therapy is intended is currently the subject of clinical trials and offers the prospect of improving outcomes in this rare but devastating disease.Keywords: immune checkpoint inhibitors, immunotherapy, malignant pleural mesothelioma, mesothelioma radiotherapy, mesothelioma surgery, trimodality therapy

Published
2022

8. Refined cut-off for TP53 immunohistochemistry improves prediction of TP53 mutation status in ovarian mucinous tumors: implications for outcome analyses

Author

Kang, Eun Young, Cheasley, Dane, LePage, Cecile, Wakefield, Matthew J., da Cunha Torres, Michelle, Rowley, Simone, Salazar, Carolina, Xing, Zhongyue, Allan, Prue, Bowtell, David D.L., Mes-Masson, Anne-Marie, Provencher, Diane M., Rahimi, Kurosh, Kelemen, Linda E., Fasching, Peter A., Doherty, Jennifer A., Goodman, Marc T., Goode, Ellen L., Deen, Suha, Pharoah, Paul D.P., Brenton, James D., Sieh, Weiva, Mateoiu, Constantina, Sundfeldt, Karin, Cook, Linda S., Le, Nhu D., Anglesio, Michael S., Gilks, C. Blake, Huntsman, David G., Kennedy, Catherine J., Traficante, Nadia, Bowtell, D., Chenevix-Trench, G., Green, A., Webb, P., DeFazio, A., Gertig, D., Traficante, N., Fereday, S., Moore, S., Hung, J., Harrap, K., Sadkowsky, T., Pandeya, N., Malt, M., Mellon, A., Robertson, R., Bergh, T. Vanden, Jones, M., Mackenzie, P., Maidens, J., Nattress, K., Chiew, Y.E., Stenlake, A., Sullivan, H., Alexander, B., Ashover, P., Brown, S., Corrish, T., Green, L., Jackman, L., Ferguson, K., Martin, K., Martyn, A., Ranieri, B., White, J., Jayde, V., Mamers, P., Bowes, L., Galletta, L., Giles, D., Hendley, J., Alsop, K., Schmidt, T., Shirley, H., Ball, C., Young, C., Viduka, S., Tran, Hoa, Bilic, Sanela, Glavinas, Lydia, Brooks, Julia, Stuart-Harris, R., Kirsten, F., Rutovitz, J., Clingan, P., Glasgow, A., Proietto, A., Braye, S., Otton, G., Shannon, J., Bonaventura, T., Stewart, J., Begbie, S., Friedlander, M., Bell, D., Baron-Hay, S., Ferrier, A., Gard, G., Nevell, D., Pavlakis, N., Valmadre, S., Young, B., Camaris, C., Crouch, R., Edwards, L., Hacker, N., Marsden, D., Robertson, G., Beale, P., Beith, J., Carter, J., Dalrymple, C., Houghton, R., Russell, P., Links, M., Grygiel, J., Hill, J., Brand, A., Byth, K., Jaworski, R., Harnett, P., Sharma, R., Wain, G., Ward, B., Papadimos, D., Crandon, A., Cummings, M., Horwood, K., Obermair, A., Perrin, L., Wyld, D., Nicklin, J., Davy, M., Oehler, M.K., Hall, C., Dodd, T., Healy, T., Pittman, K., Henderson, D., Miller, J., Pierdes, J., Blomfield, P., Challis, D., McIntosh, R., Parker, A., Brown, B., Rome, R., Allen, D., Grant, P., Hyde, S., Laurie, R., Robbie, M., Healy, D., Jobling, T., Manolitsas, T., McNealage, J., Rogers, P., Susil, B., Sumithran, E., Simpson, I., Phillips, K., Rischin, D., Fox, S., Johnson, D., Lade, S., Loughrey, M., O'Callaghan, N., Murray, W., Waring, P., Billson, V., Pyman, J., Neesham, D., Quinn, M., Underhill, C., Bell, R., Ng, L.F., Blum, R., Ganju, V., Hammond, I., Leung, Y., McCartney, A., Buck, M., Haviv, I., Purdie, D., Whiteman, D., Zeps, N., DeFazio, Anna, Kaufmann, Scott, Churchman, Michael, Gourley, Charlie, Stephens, Andrew N., Meagher, Nicola S., Ramus, Susan J., Antill, Yoland C., Campbell, Ian, Scott, Clare L., Köbel, Martin, Gorringe, Kylie L., Ryland, Georgina L., Allan, Prue E., Alsop, Kathryn, Ananda, Sumitra, Au-Yeung, George, Böhm, Maret, Brand, Alison, Chenevix-Trench, Georgia, Christie, Michael, Chiew, Yoke-Eng, Dudley, Rhiannon, Fairweather, Nicole, Fereday, Sian, Fox, Stephen B., Hacker, Neville F., Hadley, Alison M., Hendley, Joy, Ho, Gwo-Yaw, Hunter, Sally M., Jobling, Tom W., Kalli, Kimberly R., Kaufmann, Scott H., Le Page, Cecile, McNally, Orla M., McAlpine, Jessica N., Mileshkin, Linda, Pyman, Jan, Samimi, Goli, Sharma, Ragwha, and Campbell, Ian G.

Published
2021
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9. Lurbinectedin in small cell lung cancer: real-world experience of a multicentre national early access programme

Author

Alexander, M, Rogers, J, Parakh, S, Mitchell, P, Clay, TD, Kao, S, Hughes, BGM, Itchins, M, Kong, BY, Pavlakis, N, Solomon, BJ, John, T, Alexander, M, Rogers, J, Parakh, S, Mitchell, P, Clay, TD, Kao, S, Hughes, BGM, Itchins, M, Kong, BY, Pavlakis, N, Solomon, BJ, and John, T

Abstract

BACKGROUND AND AIMS: Lurbinectedin is a novel oncogenic transcription inhibitor active in several cancers, including small cell lung cancer (SCLC). We aimed to describe the first Australian experience of the clinical efficacy and tolerability of lurbinectedin for the treatment of SCLC after progression on platinum-containing therapy. METHODS: Multicentre real-world study of individuals with SCLC initiating lurbinectedin monotherapy (3.2 mg/m2 three-weekly) on an early access programme between May 2020 and December 2021. Key outcomes were clinical utilisation, efficacy and tolerability. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Outcome data were collected within the AUstralian Registry and biObank of thoRacic cAncers (AURORA). RESULTS: Data were analysed for 46 individuals across seven sites. Lurbinectedin was given as second- (83%, 38/46) or subsequent- (17%, 8/46) line therapy, mostly with prior chemoimmunotherapy (87%, 40/46). We report dose modifications (17%, 8/46), interruptions/delays (24%, 11/46), high-grade toxicities (28%, 13/46) and hospitalisations (54%, 25/46) during active treatment. The overall response rate was 33% and the disease control rate was 50%. Six-month OS was 44% (95% confidence interval (CI): 29.0-57.1). Twelve-month OS was 15% (95% CI: 6.5-26.8). From lurbinectedin first dose, the median PFS was 2.5 months (95% CI: 1.8-2.9) and OS was 4.5 months (95% CI: 3.5-7.2). From SCLC diagnosis, the median OS was 12.9 months (95% CI: 11.0-17.2). Individuals with a longer chemotherapy-free interval prior to lurbinectedin had longer PFS and OS. CONCLUSION: This real-world national experience of lurbinectedin post-platinum chemotherapy and immunotherapy for individuals with SCLC was similar to that reported in clinical trials.

Published
2024

10. A Phase II trial of alternating osimertinib and gefitinib therapy in advanced EGFR-T790M positive non-small cell lung cancer: OSCILLATE

Author

Tan, L, Brown, C, Mersiades, A, Lee, CK, John, T, Kao, S, Newnham, G, O'Byrne, K, Parakh, S, Bray, V, Jasas, K, Yip, S, Wong, SQ, Ftouni, S, Guinto, J, Chandrashekar, S, Clarke, S, Pavlakis, N, Stockler, MR, Dawson, S-J, Solomon, BJ, Tan, L, Brown, C, Mersiades, A, Lee, CK, John, T, Kao, S, Newnham, G, O'Byrne, K, Parakh, S, Bray, V, Jasas, K, Yip, S, Wong, SQ, Ftouni, S, Guinto, J, Chandrashekar, S, Clarke, S, Pavlakis, N, Stockler, MR, Dawson, S-J, and Solomon, BJ

Abstract

In this phase II, single arm trial (ACTRN12617000720314), we investigate if alternating osimertinib and gefitinib would delay the development of resistance to osimertinib in advanced, non-small cell lung cancer (NSCLC) with the epidermal growth factor receptor (EGFR) T790M mutation (n = 47) by modulating selective pressure on resistant clones. The primary endpoint is progression free-survival (PFS) rate at 12 months, and secondary endpoints include: feasibility of alternating therapy, overall response rate (ORR), overall survival (OS), and safety. The 12-month PFS rate is 38% (95% CI 27.5–55), not meeting the pre-specified primary endpoint. Serial circulating tumor DNA (ctDNA) analysis reveals decrease and clearance of the original activating EGFR and EGFR-T790M mutations which are prognostic of clinical outcomes. In 73% of participants, loss of T790M ctDNA is observed at progression and no participants have evidence of the EGFR C797S resistance mutation following the alternating regimen. These findings highlight the challenges of treatment strategies designed to modulate clonal evolution and the clinical importance of resistance mechanisms beyond suppression of selected genetic mutations in driving therapeutic escape to highly potent targeted therapies.

Published
2024

11. ASPiRATION: Australian observational cohort study of comprehensive genomic profiling in metastatic lung cancer tissue

Author

Mersiades, AJ, Solomon, BJ, Thomas, DM, Lee, CK, Cummins, MM, Sebastian, L, Ballinger, ML, Collignon, E, Turnbull, OMH, Yip, S, Morton, RL, Brown, C, Wheeler, PJ, Itchins, M, Simes, RJ, Pavlakis, N, Mersiades, AJ, Solomon, BJ, Thomas, DM, Lee, CK, Cummins, MM, Sebastian, L, Ballinger, ML, Collignon, E, Turnbull, OMH, Yip, S, Morton, RL, Brown, C, Wheeler, PJ, Itchins, M, Simes, RJ, and Pavlakis, N

Abstract

ASPiRATION is a national prospective observational cohort study assessing the feasibility, clinical and economic value of up-front tissue-based comprehensive genomic profiling (CGP) to identify actionable genomic alterations in participants with newly diagnosed metastatic non-squamous non-small-cell lung cancer in Australia. This study will enrol 1000 participants with tumor available for CGP and standard of care molecular testing (EGFR/ALK/ROS1). Participants with actionable variants may receive novel targeted treatments through ASPiRATION-specific substudies, other trials/programs. Clinical outcome data will be collected for a minimum of 2 years. Study outcomes are descriptive, including the ability of CGP to identify additional actionable variants, leading to personalized treatment recommendations, and will describe the feasibility, efficiency, cost and utility of implementation of CGP nationally.

Published
2024

12. Prognostic gene expression signature for high-grade serous ovarian cancer

Author

Bowtell, D., Chenevix-Trench, G., Green, A., Webb, P., DeFazio, A., Gertig, D., Traficante, N., Fereday, S., Moore, S., Hung, J., Harrap, K., Sadkowsky, T., Pandeya, N., Malt, M., Mellon, A., Robertson, R., Vanden Bergh, T., Jones, M., Mackenzie, P., Maidens, J., Nattress, K., Chiew, Y.E., Stenlake, A., Sullivan, H., Alexander, B., Ashover, P., Brown, S., Corrish, T., Green, L., Jackman, L., Ferguson, K., Martin, K., Martyn, A., Ranieri, B., White, J., Jayde, V., Mamers, P., Bowes, L., Galletta, L., Giles, D., Hendley, J., Alsop, K., Schmidt, T., Shirley, H., Ball, C., Young, C., Viduka, S., Tran, Hoa, Bilic, Sanela, Glavinas, Lydia, Brooks, Julia, Stuart-Harris, R., Kirsten, F., Rutovitz, J., Clingan, P., Glasgow, A., Proietto, A., Braye, S., Otton, G., Shannon, J., Bonaventura, T., Stewart, J., Begbie, S., Friedlander, M., Bell, D., Baron-Hay, S., Ferrier,a, A., Gard, G., Nevell, D., Pavlakis, N., Valmadre, S., Young, B., Camaris, C., Crouch, R., Edwards, L., Hacker, N., Marsden, D., Robertson, G., Beale, P., Beith, J., Carter, J., Dalrymple, C., Houghton, R., Russell, P., Links, M., Grygiel, J., Hill, J., Brand, A., Byth, K., Jaworski, R., Harnett, P., Sharma, R., Wain, G., Ward, B., Papadimos, D., Crandon, A., Cummings, M., Horwood, K., Obermair, A., Perrin, L., Wyld, D., Nicklin, J., Davy, M., Oehler, M.K., Hall, C., Dodd, T., Healy, T., Pittman, K., Henderson, D., Miller, J., Pierdes, J., Blomfield, P., Challis, D., McIntosh, R., Parker, A., Brown, B., Rome, R., Allen, D., Grant, P., Hyde, S., Laurie, R., Robbie, M., Healy, D., Jobling, T., Manolitsas, T., McNealage, J., Rogers, P., Susil, B., Sumithran, E., Simpson, I., Phillips, K., Rischin, D., Fox, S., Johnson, D., Lade, S., Loughrey, M., O’Callaghan, N., Murray, W., Waring, P., Billson, V., Pyman, J., Neesham, D., Quinn, M., Underhill, C., Bell, R., Ng, L.F., Blum, R., Ganju, V., Hammond, I., Leung, Y., McCartney, A., Buck, M., Haviv, I., Purdie, D., Whiteman, D., Zeps, N., Millstein, J., Budden, T., Goode, E.L., Anglesio, M.S., Talhouk, A., Intermaggio, M.P., Leong, H.S., Chen, S., Elatre, W., Gilks, B., Nazeran, T., Volchek, M., Bentley, R.C., Wang, C., Chiu, D.S., Kommoss, S., Leung, S.C.Y., Senz, J., Lum, A., Chow, V., Sudderuddin, H., Mackenzie, R., George, J., Steed, H., Koziak, J.M., Köbel, M., McNeish, I.A., Goranova, T., Ennis, D., Macintyre, G., Silva De Silva, D., Ramón y Cajal, T., García-Donas, J., Hernando Polo, S., Rodriguez, G.C., Cushing-Haugen, K.L., Harris, H.R., Greene, C.S., Zelaya, R.A., Behrens, S., Fortner, R.T., Sinn, P., Herpel, E., Lester, J., Lubiński, J., Oszurek, O., Tołoczko, A., Cybulski, C., Menkiszak, J., Pearce, C.L., Pike, M.C., Tseng, C., Alsop, J., Rhenius, V., Song, H., Jimenez-Linan, M., Piskorz, A.M., Gentry-Maharaj, A., Karpinskyj, C., Widschwendter, M., Singh, N., Kennedy, C.J., Harnett, P.R., Gao, B., Johnatty, S.E., Sayer, R., Boros, J., Winham, S.J., Keeney, G.L., Kaufmann, S.H., Larson, M.C., Luk, H., Hernandez, B.Y., Thompson, P.J., Wilkens, L.R., Carney, M.E., Trabert, B., Lissowska, J., Brinton, L., Sherman, M.E., Bodelon, C., Hinsley, S., Lewsley, L.A., Glasspool, R., Banerjee, S.N., Stronach, E.A., Haluska, P., Ray-Coquard, I., Mahner, S., Winterhoff, B., Slamon, D., Levine, D.A., Kelemen, L.E., Benitez, J., Chang-Claude, J., Gronwald, J., Wu, A.H., Menon, U., Goodman, M.T., Schildkraut, J.M., Wentzensen, N., Brown, R., Berchuck, A., deFazio, A., Gayther, S.A., García, M.J., Henderson, M.J., Rossing, M.A., Beeghly-Fadiel, A., Fasching, P.A., Orsulic, S., Karlan, B.Y., Konecny, G.E., Huntsman, D.G., Bowtell, D.D., Brenton, J.D., Doherty, J.A., Pharoah, P.D.P., and Ramus, S.J.

Published
2020
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13. Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): a multicentre, open-label, phase 3, randomised, controlled trial

Author

Ahn, JB, Asselah, J, Badarinath, S, Baijal, S, Begbie, S, Berry, S, Canon, JL, Carbone, RG, Cervantes, A, Cha, YJ, Chang, K, Chaudhry, A, Chmielowska, E, Cho, SH, Chu, D, Couture, F, Cultrera, J, Cunningham, D, Van Cutsem, E, Cuyle, PJ, Davies, J, Dowden, S, Dvorkin, M, Ganju, V, Garcia, RV, Kerr, R, Kim, TY, King, K, Kortmansky, J, Kozloff, M, Lam, KO, Lee, J, Lee, AS, Lesperance, B, Luppi, G, Ma, B, Maiello, E, Mandanas, R, Marshall, J, Marx, G, Mullamitha, S, Nechaeva, M, Park, JO, Pavlakis, N, Ponce, CG, Potemski, P, Raouf, S, Reeves, J, Segal, N, Siena, S, Smolin, A, Streb, JO, Strickland, A, Szutowicz-Zielinska, E, Tabernero, JM, Tan, B, Valera, JS, Van den Eynde, M, Vergauwe, P, Vickers, M, Womack, M, Wroblewska, M, Young, R, Eng, Cathy, Kim, Tae Won, Bendell, Johanna, Argilés, Guillem, Tebbutt, Niall C, Di Bartolomeo, Maria, Falcone, Alfredo, Fakih, Marwan, Kozloff, Mark, Segal, Neil H, Sobrero, Alberto, Yan, Yibing, Chang, Ilsung, Uyei, Anne, Roberts, Louise, and Ciardiello, Fortunato

Published
2019
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15. P2.10-01 ALKTERNATE: A Pilot Study Alternating Lorlatinib with Crizotinib in Patients with ALK+ NSCLC and ALK-inhibitor Resistance

Author

Itchins, M., primary, Liang, S., additional, Brown, C., additional, Barnes, T., additional, Marx, G., additional, Chin, V., additional, Kao, S., additional, Yip, P.Y., additional, Mersiades, A.J., additional, Nagrial, A., additional, Bray, V., additional, Peters, G., additional, Parakh, S., additional, John, T., additional, Li, M., additional, Li, B.T., additional, McKay, M., additional, Molloy, M., additional, O'Byrne, K., additional, Lee, C., additional, Gill, A., additional, Solomon, B.J., additional, and Pavlakis, N., additional

Published
2023
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16. MA17.05 Real World Outcomes of Immunotherapy (IO) for Pleural MESOthelioma in Australia - RIOMeso

Author

McNamee, N., primary, Harvey, C., additional, Gray, L., additional, Khoo, T., additional, Lingam, L., additional, Zhang, B., additional, Clay, T., additional, Arulananda, S., additional, Itchins, M., additional, Pavlakis, N., additional, Kao, S., additional, Bowyer, S., additional, Chin, V., additional, Warburton, L., additional, da Silva, I., additional, John, T., additional, Solomon, B., additional, Alexander, M., additional, and Nagrial, A., additional

Published
2023
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17. P2.11-05 SHERLOCK: Phase II Trial of Upfront Sotorasib with Chemotherapy and Bevacizumab for Advanced NSCLC with KRASG12C Mutation

Author

Lee, C., primary, Pavlakis, N., additional, Zhou, D.D.-X., additional, Brown, C., additional, Hughes, B.G.M., additional, Yip, S., additional, Bray, V.J., additional, Daley, F.T., additional, Roberts-Thomson, R., additional, Cummins, M.M., additional, John, T., additional, Solomon, B.J., additional, and Mitchell, P., additional

Published
2023
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18. Brief Report: Real-world toxicity and survival of combination immunotherapy in pleural mesothelioma - RIOMeso

Author

McNamee, N., primary, Harvey, C., additional, Gray, L., additional, Khoo, T., additional, Lingam, L., additional, Zhang, B., additional, Nindra, U., additional, Yip, P.Y., additional, Pal, A., additional, Clay, T., additional, Arulananda, S., additional, Itchins, M., additional, Pavlakis, N., additional, Kao, S., additional, Bowyer, S., additional, Chin, V., additional, Warburton, L., additional, Pires da Silva, I., additional, John, T., additional, Solomon, B., additional, Alexander, M., additional, and Nagrial, A., additional

Published
2023
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21. 60 CONTACT-01: Efficacy and safety from a phase III study of atezolizumab (atezo) + cabozantinib (cabo) vs docetaxel (doc) monotherapy in patients (pts) with metastatic NSCLC (mNSCLC) previously treated with checkpoint inhibitors and chemotherapy

Author

Neal, J., primary, Pavlakis, N., additional, Kim, S-W., additional, Goto, Y., additional, Lim, S.M., additional, Mountzios, G., additional, Fountzilas, E., additional, Mochalova, A., additional, Christoph, D.C.C., additional, Bearz, A., additional, Quantin, X., additional, Palmero, R., additional, Antic, V., additional, Chun, E., additional, Edubilli, T. Rao, additional, Lin, Y-C., additional, Huseni, M., additional, Scheffold, C., additional, Vervaet, P., additional, and Newsom-Davis, T., additional

Published
2023
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22. A phase III randomized trial of adding topical nitroglycerin to first-line chemotherapy for advanced nonsmall-cell lung cancer: the Australasian lung cancer trials group NITRO trial

Author

Hughes, Brett, Boyer, Michael, Briscoe, Karen, Davidson, Andrew, Begbie, Stephen, Abdi, Ehtesham, Crombie, Catherine, Long, Jeremy, Jasas, Kevin, Lewis, Craig, Boyce, Adam, Vama, Suresh, Broad, Adam, Broaddge, Vy., Gibbs, David, Blum, Robert, McLachlan, Sue-Anne, Haydon, Andrew, Bray, Victoria, Vardy, Janette, Mallesara, Girish, Lowenthal, Ray, Asghari, Ray, Tiley, Susan, Hayes, Theresa, Islam, Mohammed, Ackland, Steven, Adams, Jacqui, Pavlakis, Nick, Stockler, Martin, Muljadi, Nick, Coskinas, Xanthi, Chinchen, Sarah, Chan, Matthew, Tognela, Annette, Ferraro, Danielle, Cosman, Rasha, Davidson, A., Veillard, A.-S., Tognela, A., Chan, M.M.K., Hughes, B.G.M., Boyer, M., Briscoe, K., Begbie, S., Abdi, E., Crombie, C., Long, J., Boyce, A., Lewis, C.R., Varma, S., Broad, A., Muljadi, N., Chinchen, S., Espinoza, D., Coskinas, X., Pavlakis, N., Millward, M., and Stockler, M.R.

Published
2015
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24. 347P Real-world efficacy of first-line therapy in wild-type non-small cell lung cancer (NSCLC) patients with brain metastases

Author

Kong, B., primary, Wei, J., additional, Smith, S., additional, Chan, W.Y., additional, Harden, S.V., additional, Khou, V., additional, Alexander, M., additional, Brown, C., additional, Itchins, M., additional, Lee, J., additional, Mersiades, A., additional, Gray, L., additional, Boyer, M., additional, Pavlakis, N., additional, Clarke, S., additional, Jayamanne, D., additional, and Kao, S.C-H., additional

Published
2022
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26. EP16.03-005 Australian Non-Small Cell Lung Cancer (NSCLC) Biomarker Testing Practices - A Survey of Medical Oncologists and Pathologists

Author

Gard, G., primary, Kao, S., additional, Solomon, B., additional, Pavlakis, N., additional, Cooper, W., additional, Millward, M., additional, Roberts-Thomson, R., additional, Nott, L., additional, Hughes, B., additional, Hong, W., additional, Dumas, M., additional, Ramanujam, S., additional, Wang, A., additional, Elkouly, E., additional, Gibbs, P., additional, and Markman, B., additional

Published
2022
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27. EP04.01-023 Development of an Australia and New Zealand Lung Cancer Clinical Quality Registry (ANZLCR)

Author

Stirling, R., primary, Smith, S., additional, Brand, M., additional, Harden, S., additional, Briggs, L., additional, Leigh, L., additional, Brims, F., additional, Brooke, M., additional, Brunelli, V., additional, Chia, C., additional, Dawkins, P., additional, Lawrenson, R., additional, Duffy, M., additional, Evans, S., additional, Leong, T., additional, Marshall, H., additional, Patel, D., additional, Pavlakis, N., additional, Philip, J., additional, Rankin, N., additional, Singhal, N., additional, Stone, E., additional, Tay, R., additional, Vinod, S., additional, Windsor, M., additional, Wright, G., additional, Leong, D., additional, and Zalcberg, J., additional

Published
2022
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30. 623P Phase II trial of vemurafenib (VEM) and cobimetinib (COB) in BRAF V600-mutated solid tumours and first-line (1L) non-small cell lung cancer (NSCLC): Australian molecular screening and therapeutics (MoST) substudy 12

Author

Lin, F.P., Mersiades, A., Lee, J., Xu, W., Chinchen, S., Charakidis, M., Thavaneswaran, S., Hughes, B.G.M., Underhill, C.R., Takhar, H.S., Harrup, R., Nagrial, A., Millward, M., Desai, J., Espinoza, D., Lee, C.K., Solomon, B.J., Simes, J., Pavlakis, N., and Thomas, D.

Published
2024
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31. MyD88 and TLR4 Expression in Epithelial Ovarian Cancer

Author

Block, Matthew S., Vierkant, Robert A., Rambau, Peter F., Winham, Stacey J., Wagner, Philipp, Traficante, Nadia, Tołoczko, Aleksandra, Tiezzi, Daniel G., Taran, Florin Andrei, Sinn, Peter, Sieh, Weiva, Sharma, Raghwa, Rothstein, Joseph H., Cajal, Teresa Ramón y, Paz-Ares, Luis, Oszurek, Oleg, Orsulic, Sandra, Ness, Roberta B., Nelson, Gregg, Modugno, Francesmary, Menkiszak, Janusz, McGuire, Valerie, McCauley, Bryan M., Mack, Marie, Lubiński, Jan, Longacre, Teri A., Li, Zheng, Lester, Jenny, Kennedy, Catherine J., Kalli, Kimberly R., Jung, Audrey Y., Johnatty, Sharon E., Jimenez-Linan, Mercedes, Jensen, Allan, Intermaggio, Maria P., Hung, Jillian, Herpel, Esther, Hernandez, Brenda Y., Hartkopf, Andreas D., Harnett, Paul R., Ghatage, Prafull, García-Bueno, José M., Gao, Bo, Fereday, Sian, Eilber, Ursula, Edwards, Robert P., de Sousa, Christiani B., de Andrade, Jurandyr M., Chudecka-Głaz, Anita, Chenevix-Trench, Georgia, Cazorla, Alicia, Brucker, Sara Y., Alsop, Jennifer, Whittemore, Alice S., Steed, Helen, Staebler, Annette, Moysich, Kirsten B., Menon, Usha, Koziak, Jennifer M., Kommoss, Stefan, Kjaer, Susanne K., Kelemen, Linda E., Karlan, Beth Y., Huntsman, David G., Hφgdall, Estrid, Gronwald, Jacek, Goodman, Marc T., Gilks, Blake, García, María José, Fasching, Peter A., de Fazio, Anna, Deen, Suha, Chang-Claude, Jenny, Candido dos Reis, Francisco J., Campbell, Ian G., Brenton, James D., Bowtell, David D., Benítez, Javier, Pharoah, Paul D.P., Köbel, Martin, Ramus, Susan J., Goode, Ellen L., Bowtell, D., Chenevix-Trench, G., Green, A., Webb, P., DeFazio, A., Gertig, D., Traficante, N., Fereday, S., Moore, S., Hung, J., Harrap, K., Sadkowsky, T., Pandeya, N., Malt, M., Mellon, A., Robertson, R., Bergh, Vanden T., Jones, M., Mackenzie, P., Maidens, J., Nattress, K., Chiew, Y. E., Stenlake, A., Sullivan, H., Alexander, B., Ashover, P., Brown, S., Corrish, T., Green, L., Jackman, L., Ferguson, K., Martin, K., Martyn, A., Ranieri, B., White, J., Jayde, V., Mamers, P., Bowes, L., Galletta, L., Giles, D., Hendley, J., Alsop, K., Schmidt, T., Shirley, H., Ball, C., Young, C., Viduka, S., Tran, Hoa, Bilic, Sanela, Glavinas, Lydia, Brooks, Julia, Stuart-Harris, R., Kirsten, F., Rutovitz, J., Clingan, P., Glasgow, A., Proietto, A., Braye, S., Otton, G., Shannon, J., Bonaventura, T., Stewart, J., Begbie, S., Friedlander, M., Bell, D., Baron-Hay, S., Ferrier, A., Gard, G., Nevell, D., Pavlakis, N., Valmadre, S., Young, B., Camaris, C., Crouch, R., Edwards, L., Hacker, N., Marsden, D., Robertson, G., Beale, P., Beith, J., Carter, J., Dalrymple, C., Houghton, R., Russell, P., Links, M., Grygiel, J., Hill, J., Brand, A., Byth, K., Jaworski, R., Harnett, P., Sharma, R., Wain, G., Ward, B., Papadimos, D., Crandon, A., Cummings, M., Horwood, K., Obermair, A., Perrin, L., Wyld, D., Nicklin, J., Davy, M., Oehler, M. K., Hall, C., Dodd, T., Healy, T., Pittman, K., Henderson, D., Miller, J., Pierdes, J., Blomfield, P., Challis, D., McIntosh, R., Parker, A., Brown, B., Rome, R., Allen, D., Grant, P., Hyde, S., Laurie, R., Robbie, M., Healy, D., Jobling, T., Manolitsas, T., McNealage, J., Rogers, P., Susil, B., Sumithran, E., Simpson, I., Phillips, K., Rischin, D., Fox, S., Johnson, D., Lade, S., Loughrey, M., OʼCallaghan, N., Murray, W., Waring, P., Billson, V., Pyman, J., Neesham, D., Quinn, M., Underhill, C., Bell, R., Ng, L. F., Blum, R., Ganju, V., Hammond, I., Leung, Y., McCartney, A., Buck, M., Haviv, I., Purdie, D., Whiteman, D., and Zeps, N.

Published
2018
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33. P-133 Clinical responses in pancreaticobiliary cancer patients who received bintrafusp alfa (BA) or BA plus CXCR1/2 inhibitor (SX-682) plus CEA/MUC1-targted vaccine (CV301)

Author

Redman, J., primary, Spira, A., additional, Javle, M., additional, Kelly, K., additional, Pavlakis, N., additional, Jehl, G., additional, Gatti-Mays, M., additional, Cordes, L., additional, Alewine, C., additional, Pico-Navarro, C., additional, Zebala, J., additional, Ito, R., additional, Marte, J., additional, Strauss, J., additional, Floudas, C., additional, Pastor, D., additional, Francis, D., additional, Redmond, E., additional, Gulley, J., additional, and Schlom, J., additional

Published
2022
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34. DREAM3R: DuRvalumab With chEmotherapy as First Line treAtment in Advanced Pleural Mesothelioma: A Phase 3 Randomised Trial

Author

Forde, P., Kindler, H., Zauderer, M., Sun, Z., Ramalingam, S., Anagnostou, V., Brahmer, J.r., Nowak, A.k., Kok, P.s., Brown, C., Yip, S., Cook, A., Lesterhuis, W.j., Hughes, B.g.m., Pavlakis, N., Stockler, M.r., O'Byrne, K.J., Forde, P., Kindler, H., Zauderer, M., Sun, Z., Ramalingam, S., Anagnostou, V., Brahmer, J.r., Nowak, A.k., Kok, P.s., Brown, C., Yip, S., Cook, A., Lesterhuis, W.j., Hughes, B.g.m., Pavlakis, N., Stockler, M.r., and O'Byrne, K.J.

Abstract

Purpose/Objective(s): • Platinum-based chemotherapy with pemetrexed is an appropriate first line treatment option for unresectable malignant pleural mesothelioma (MPM) • The DREAM¹ and PrE0505² Phase II trials combined durvalumab (PD-L1 inhibitor) with a platinum and pemetrexed both exceeding pre-specified response with acceptable toxicity • CheckMate 7433 recently reported an overall survival benefit with ipilimumab plus nivolumab vs. chemotherapy (HR 0.74, 95% CI 0.50 to 0.91). However, this benefit was less apparent in the 75% of patients with epithelioid histology (HR 0.86, 95% CI 0.69 to 1.08) • Clinical trials to further explore optimal first line treatment for MPM with immunotherapy are needed Materials/Methods International, open label, randomised (2:1), multi-centre, phase 3 trial • 480 patients (320 durvalumab and chemotherapy, 160 chemotherapy) to be recruited over 27 months and followed for another 24 months • This provides over 85% power if the true hazard ratio for overall survival is 0.70 with 2-sided alpha of 0.05, assuming a median survival of 15 months in the chemotherapy group, 21.4 months in the durvalumab and chemotherapy group, with an allowance for crossover Results TBD Conclusion TBD

Published
2022

35. PEARL: A randomised phase 3 trial of palliative care early in advanced lung cancers (ALTG/TOGA 13/008).

Author

Mileshkin L.R., Yoong J., Eggins R., Philip J., Brown C., Wright G.M., Tognela A., Blinman P., Poon P., Nowak A.K., Oar A., Pavlakis N., Walker M., Chong J., Jurkovic H., Srivastav R.K., Abdi E.A., Mersiades A., Thomas R., Stockler M.R., Mileshkin L.R., Yoong J., Eggins R., Philip J., Brown C., Wright G.M., Tognela A., Blinman P., Poon P., Nowak A.K., Oar A., Pavlakis N., Walker M., Chong J., Jurkovic H., Srivastav R.K., Abdi E.A., Mersiades A., Thomas R., and Stockler M.R.

Abstract

Background: Early referral to palliative care was associated with improved health-related quality of life (HRQL) and overall survival (OS) in a US phase 3 trial in lung cancer patients (pts). International studies in mixed cancer types have reported conflicting results. PEARL aimed to determine whether early referral to palliative care would improve HRQL, OS, and resource use in Australian pts with recently diagnosed, advanced thoracic cancers. Method(s): Eligible participants (pts) in this unblinded, multi-centre, randomised, phase 3 trial had advanced thoracic cancers diagnosed within 60 days, and the ability to complete patient-rated outcome measures (PROMS). Pts were randomly allocated to early referral to palliative care (ER) or referral at clinician's discretion (DR). All pts received standard oncological care. PROMS were completed at baseline, every 3-4 weeks for 6 months, then 6-8 weekly. The primary objective was to determine the frequency of sustained, substantial improvements in HRQL, defined as a 5-point improvement in the FACT-L Trial Outcome Index (TOI) maintained for at least 2 consecutive assessments. Secondary outcomes included OS, documentation of advanced care plan (ACP), PROM scores at 12 weeks, anxiety/depression (PROMIS-ED), lung cancer symptoms (FACT-L), global HRQL (ICECAP-SCM), carer-satisfaction and burden, and understanding of illness and prognosis. The accrual target of 200 gave 80% power (alpha 0.05) to detect an absolute improvement of 20% in the proportion of pts achieving the primary endpoint. Result(s): 113 pts and 78 carers were recruited when the trial closed for slow accrual. Pt characteristics were well balanced: 88 (75%) had NSCLC, 18 (16%) small cell and 7 (6%) mesothelioma. Median age was 69 (IQR 62-74), 63 (56%) were male; systemic anti-cancer therapy ongoing or planned in 88 (78%). Median follow-up was 30 months. First consultations with a palliative care specialist within 60 days of diagnosis occurred in more pts assigned E

Published
2022

36. The Management of Unresectable, Advanced Gastrointestinal Stromal Tumours

Author

Foo, T, Goldstein, D, Segelov, E, Shapiro, J, Pavlakis, N, Desai, J, Yip, D, Zalcberg, J, Price, TJ, Nagrial, A, Chantrill, L, Burge, M, Karapetis, CS, Tebbutt, N, Roy, AC, Foo, T, Goldstein, D, Segelov, E, Shapiro, J, Pavlakis, N, Desai, J, Yip, D, Zalcberg, J, Price, TJ, Nagrial, A, Chantrill, L, Burge, M, Karapetis, CS, Tebbutt, N, and Roy, AC

Abstract

Gastrointestinal stromal tumours (GISTs) are the most common gastrointestinal tract mesenchymal tumours. Tyrosine kinase inhibitors (TKIs) have transformed the management of advanced GIST. Imatinib was the first TKI to gain approval as management for patients with advanced GIST, establishing a new standard of care. Since then, as a result of several trials including the GRID and INVICTUS studies, we now have five lines of approved targeted therapy, including imatinib, sunitinib, regorafenib, ripretinib and avapritinib for the treatment of unresectable, advanced GISTs. In this review, the Australasian Gastrointestinal Trials Group (AGITG) provide an overview of the key trials that have changed clinical practice, discuss the molecular drivers of GISTs, the importance of molecular testing and directing therapy according to molecular targets, as well as future strategies in the management of advanced GISTs.

Published
2022

37. Lung cancer treatment patterns and factors relating to systemic therapy use in Australia

Author

Ngo, P, Goldsbury, DE, Karikios, D, Yap, S, Yap, ML, Egger, S, O'Connell, DL, Ball, D, Fong, KM, Pavlakis, N, Rankin, NM, Vinod, S, Canfell, K, Weber, MF, Ngo, P, Goldsbury, DE, Karikios, D, Yap, S, Yap, ML, Egger, S, O'Connell, DL, Ball, D, Fong, KM, Pavlakis, N, Rankin, NM, Vinod, S, Canfell, K, and Weber, MF

Abstract

AIM: Systemic therapies for lung cancer are rapidly evolving. This study aimed to describe lung cancer treatment patterns in New South Wales, Australia, prior to the introduction of immunotherapy and latest-generation targeted therapies. METHODS: Systemic therapy utilization and treatment-related factors were examined for participants in the New South Wales 45 and Up Study with incident lung cancer ascertained by record linkage to the New South Wales Cancer Registry (2006-2013). Systemic therapy receipt to June 2016 was determined using medical and pharmaceutical claims data from Services Australia, and in-patient hospital records. Factors related to treatment were identified using competing risks regressions. RESULTS: A total of 1,116 lung cancer cases were identified with a mean age at diagnosis of 72 years and median survival of 10.6 months. Systemic therapy was received by 45% of cases. Among 400 cases with metastatic non-small cell lung cancer, 51% and 28% received first- and second-line systemic therapy, respectively. Among 112 diagnosed with small-cell lung cancer, 79% and 29% received first- and second-line systemic therapy. The incidence of systemic therapy was lower for participants with indicators of poor performance status, lower educational attainment, and those who lived in areas of socioeconomic disadvantage; and was higher for participants with small-cell lung cancer histology or higher body mass index. CONCLUSION: This population-based Australian study identified patterns of systemic therapy use for lung cancer, particularly small-cell lung cancer. Despite a universal healthcare system, the analysis revealed socioeconomic disparities in health service utilization and relatively low utilization of systemic therapy overall.

Published
2022

38. Vigilance for carcinoid heart disease is still required in the era of somatostatin analogues: Lessons from a case series

Author

Chan, DL, Pavlakis, N, Crumbaker, M, Lawrence, B, Barber, C, Price, TJ, Michael, M, Oberg, K, Chan, DL, Pavlakis, N, Crumbaker, M, Lawrence, B, Barber, C, Price, TJ, Michael, M, and Oberg, K

Abstract

AIM: Carcinoid heart disease (CHD) is a well-documented complication of neuroendocrine tumors (NETs) due to secreted hormones causing fibrosis. Somatostatin analogues (SSAs) can decrease hormonal secretion and inhibit tumor growth. The reported incidence of CHD has decreased as SSA use has increased. We describe a series of patients who have developed CHD even though they were treated with SSA therapy. METHODS: Nine patients were seen in four centers in Australia and New Zealand. The average duration of follow-up from diagnosis was 39 months. RESULTS: Three patients had Grade 1 and six Grade 2 disease by World Health Organization 2010 criteria. All patients had no CHD symptoms at baseline and started SSA therapy soon after diagnosis, yet developed significant, symptomatic cardiac dysfunction in their disease course. The median time from NET diagnosis to SSA initiation was 1 month, and median time from NET diagnosis to CHD diagnosis was 23 months (range 4-52). All patients who were tested had persistently increased hormonal levels (chromogranin A, urinary 5-hydroxyindolacetic acid). CONCLUSIONS: The good symptomatic control afforded by SSAs should not lead to reduced vigilance in screening for CHD, especially in patients with persistently elevated hormonal assays. Clinicians should consider regular echocardiographic screening in patients with a secretory syndrome.

Published
2022

39. Asian Thoracic Oncology Research Group (ATORG) Expert Consensus Statement on MET Alterations in NSCLC: Diagnostic and Therapeutic Considerations

Author

Ahn, M-J, Mendoza, MJL, Pavlakis, N, Kato, T, Soo, RA, Kim, D-W, Liam, CK, Hsia, T-C, Lee, CK, Reungwetwattana, T, Geater, S, Chan, OSH, Prasongsook, N, Solomon, BJ, Nguyen, TTH, Kozuki, T, Yang, JC-H, Wu, Y-L, Kam, TS, Tan, DS-W, Yatabe, Y, Ahn, M-J, Mendoza, MJL, Pavlakis, N, Kato, T, Soo, RA, Kim, D-W, Liam, CK, Hsia, T-C, Lee, CK, Reungwetwattana, T, Geater, S, Chan, OSH, Prasongsook, N, Solomon, BJ, Nguyen, TTH, Kozuki, T, Yang, JC-H, Wu, Y-L, Kam, TS, Tan, DS-W, and Yatabe, Y

Abstract

Non-small cell lung cancer (NSCLC) is a heterogeneous disease, with many oncogenic driver mutations, including de novo mutations in the Mesenchymal Epithelial Transition (MET) gene (specifically in Exon 14 [ex14]), that lead to tumourigenesis. Acquired alterations in the MET gene, specifically MET amplification is also associated with the development of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in patients with EGFR-mutant NSCLC. Although MET has become an actionable biomarker with the availability of MET-specific inhibitors in selected countries, there is differential accessibility to diagnostic platforms and targeted therapies across countries in Asia-Pacific (APAC). The Asian Thoracic Oncology Research Group (ATORG), an interdisciplinary group of experts from Australia, Hong Kong, Japan, Korea, Mainland China, Malaysia, the Philippines, Singapore, Taiwan, Thailand and Vietnam, discussed testing for MET alterations and considerations for using MET-specific inhibitors at a consensus meeting in January 2022, and in subsequent offline consultation. Consensus recommendations are provided by the ATORG group to address the unmet need for standardised approaches to diagnosing MET alterations in NSCLC and for using these therapies. MET inhibitors may be considered for first-line or second or subsequent lines of treatment for patients with advanced and metastatic NSCLC harbouring MET ex14 skipping mutations; MET ex14 testing is preferred within multi-gene panels for detecting targetable driver mutations in NSCLC. For patients with EGFR-mutant NSCLC and MET amplification leading to EGFR TKI resistance, enrolment in combination trials of EGFR TKIs and MET inhibitors is encouraged.

Published
2022

40. Development of an Australia and New Zealand Lung Cancer Clinical Quality Registry: a protocol paper

Author

Smith, S, Brand, M, Harden, S, Briggs, L, Leigh, L, Brims, F, Brooke, M, Brunelli, VN, Chia, C, Dawkins, P, Lawrenson, R, Duffy, M, Evans, S, Leong, T, Marshall, H, Patel, D, Pavlakis, N, Philip, J, Rankin, N, Singhal, N, Stone, E, Tay, R, Vinod, S, Windsor, M, Wright, GM, Leong, D, Zalcberg, J, Stirling, RG, Smith, S, Brand, M, Harden, S, Briggs, L, Leigh, L, Brims, F, Brooke, M, Brunelli, VN, Chia, C, Dawkins, P, Lawrenson, R, Duffy, M, Evans, S, Leong, T, Marshall, H, Patel, D, Pavlakis, N, Philip, J, Rankin, N, Singhal, N, Stone, E, Tay, R, Vinod, S, Windsor, M, Wright, GM, Leong, D, Zalcberg, J, and Stirling, RG

Abstract

INTRODUCTION: Lung cancer is the leading cause of cancer mortality, comprising the largest national cancer disease burden in Australia and New Zealand. Regional reports identify substantial evidence-practice gaps, unwarranted variation from best practice, and variation in processes and outcomes of care between treating centres. The Australia and New Zealand Lung Cancer Registry (ANZLCR) will be developed as a Clinical Quality Registry to monitor the safety, quality and effectiveness of lung cancer care in Australia and New Zealand. METHODS AND ANALYSIS: Patient participants will include all adults >18 years of age with a new diagnosis of non-small-cell lung cancer (NSCLC), SCLC, thymoma or mesothelioma. The ANZLCR will register confirmed diagnoses using opt-out consent. Data will address key patient, disease, management processes and outcomes reported as clinical quality indicators. Electronic data collection facilitated by local data collectors and local, state and federal data linkage will enhance completeness and accuracy. Data will be stored and maintained in a secure web-based data platform overseen by registry management. Central governance with binational representation from consumers, patients and carers, governance, administration, health department, health policy bodies, university research and healthcare workers will provide project oversight. ETHICS AND DISSEMINATION: The ANZLCR has received national ethics approval under the National Mutual Acceptance scheme. Data will be routinely reported to participating sites describing performance against measures of agreed best practice and nationally to stakeholders including federal, state and territory departments of health. Local, regional and (bi)national benchmarks, augmented with online dashboard indicator reporting will enable local targeting of quality improvement efforts.

Published
2022

44. Optimal management of bone metastases in breast cancer patients

Author

Wong MH and Pavlakis N

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

MH Wong, N PavlakisDepartment of Medical Oncology, Royal North Shore Hospital, Sydney, NSW, AustraliaAbstract: Bone metastasis in breast cancer is a significant clinical problem. It not only indicates incurable disease with a guarded prognosis, but is also associated with skeletal-related morbidities including bone pain, pathological fractures, spinal cord compression, and hypercalcemia. In recent years, the mechanism of bone metastasis has been further elucidated. Bone metastasis involves a vicious cycle of close interaction between the tumor and the bone microenvironment. In patients with bone metastases, the goal of management is to prevent further skeletal-related events, manage complications, reduce bone pain, and improve quality of life. Bisphosphonates are a proven therapy for the above indications. Recently, a drug of a different class, the RANK ligand antibody, denosumab, has been shown to reduce skeletal-related events more than the bisphosphonate, zoledronic acid. Other strategies of clinical value may include surgery, radiotherapy, radiopharmaceuticals, and, of course, effective systemic therapy. In early breast cancer, bisphosphonates may have an antitumor effect and prevent both bone and non-bone metastases. Whilst two important Phase III trials with conflicting results have led to controversy in this topic, final results from these and other key Phase III trials must still be awaited before a firm conclusion can be drawn about the use of bisphosphonates in this setting. Advances in bone markers, predictive biomarkers, multi-imaging modalities, and the introduction of novel agents have ushered in a new era of proactive management for bone metastases in breast cancer.Keywords: breast cancer, bone metastases, bisphosphonates, denosumab, biomarkers, optimal management

Published
2011

46. DREAM3R: DuRvalumab With chEmotherapy as First Line treAtment in Advanced Pleural Mesothelioma: A Phase 3 Randomised Trial

Author

Forde, P., primary, Kindler, H., additional, Zauderer, M., additional, Sun, Z., additional, Ramalingam, S., additional, Anagnostou, V., additional, Brahmer, J.R., additional, Nowak, A.K., additional, Kok, P.S., additional, Brown, C., additional, Yip, S., additional, Cook, A., additional, Lesterhuis, W.J., additional, Hughes, B.G.M., additional, Pavlakis, N., additional, Stockler, M.R., additional, and O'Byrne, K.J., additional

Published
2022
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