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Purpose: Precision oncology has transformed the management of advanced cancers through implementation of advanced molecular profiling technologies to identify increasingly defined subsets of patients and match them to appropriate therapy. We report outcomes of a prospective molecular profiling study in a high-volume Asian tertiary cancer center., Patients and Methods: Patients with advanced cancer were enrolled onto a prospective protocol for genomic profiling, the Individualized Molecular Profiling for Allocation to Clinical Trials Singapore study, at the National Cancer Center Singapore. Primary objective was to identify molecular biomarkers in patient's tumors for allocation to clinical trials. The study commenced in February 2012 and is ongoing, with the results of all patients who underwent multiplex next-generation sequencing (NGS) testing until December 2018 presented here. The results were discussed at a molecular tumor board where recommendations for allocation to biomarker-directed trials or targeted therapies were made., Results: One thousand fifteen patients were enrolled with a median age of 58 years (range 20-83 years). Most common tumor types were lung adenocarcinoma (26%), colorectal cancer (15%), and breast cancer (12%). A total of 1,064 NGS assays were performed, on fresh tumor tissue for 369 (35%) and archival tumor tissue for 687 (65%) assays. TP53 (39%) alterations were most common, followed by EGFR (21%), KRAS (14%), and PIK3CA (10%). Of 405 NGS assays with potentially actionable alterations, 111 (27%) were allocated to a clinical trial after molecular tumor board and 20 (4.9%) were enrolled on a molecularly matched clinical trial. Gene fusions were detected in 23 of 311 (7%) patients tested, including rare fusions in new tumor types and known fusions in rare tumors., Conclusion: Individualized Molecular Profiling for Allocation to Clinical Trials Singapore demonstrates the feasibility of a prospective broad molecular profiling program in an Asian tertiary cancer center, with the ability to develop and adapt to a dynamic landscape of precision oncology., Competing Interests: Aaron C. Tan Honoraria: Amgen, Thermo Fisher Scientific Travel, Accommodations, Expenses: ASLAN Pharmaceuticals, Illumina Tira J. Tan Stock and Other Ownership Interests: Immunomedics Honoraria: AstraZeneca, Roche/Genentech Consulting or Advisory Role: AstraZeneca, Lilly, Pfizer, DKSH, Novartis Speakers' Bureau: Novartis Research Funding: Bayer, Novartis, AstraZeneca, Odonate Therapeutics, Synthon Travel, Accommodations, Expenses: AstraZeneca, Eisai Matthew C. H. Ng Honoraria: MSD Oncology, Taiho Pharmaceutical, ASLAN Pharmaceuticals, Lilly Consulting or Advisory Role: MSD Oncology, Bristol Myers Squibb, Novartis, Merck Speakers' Bureau: Lilly Research Funding: ASLAN Pharmaceuticals Travel, Accommodations, Expenses: MSD Oncology, Taiho Pharmaceutical, Bristol Myers Squibb David W. M. Tai Honoraria: Bristol Myers Squibb, Eisai Consulting or Advisory Role: Bristol Myers Squibb, Eisai Speakers' Bureau: Ipsen, Bristol Myers Squibb, Eisai, Roche Research Funding: Bristol-Myers Squibb, Sirtex Medical, Novartis. Justina Y. C. Lam Honoraria: AstraZeneca Consulting or Advisory Role: AstraZeneca Research Funding: Bayer, Merus, Bristol Myers Squibb Travel, Accommodations, Expenses: Lilly Bien-Soo Tan Research Funding: Boston Scientific Rebecca Alexandra Dent Honoraria: Roche/Genentech, AstraZeneca, Pfizer, MSD Consulting or Advisory Role: Roche, Pfizer, Merck, Eisai, AstraZeneca, Novartis Travel, Accommodations, Expenses: Roche, Pfizer, Amgen, Merck Yoon-Sim Yap Honoraria: Novartis, Lilly, Pfizer, AstraZeneca, Eisai, MSD, Inivata Consulting or Advisory Role: Novartis, Lilly, Pfizer, AstraZeneca, Eisai, MSD, Inivata Travel, Accommodations, Expenses: Pfizer, AstraZeneca, Eisai, Lilly, Roche, Novartis Iain B. H. Tan Honoraria: Amgen, Roche, Merck Serono, MSD Consulting or Advisory Role: Amgen, Roche, Merck Serono, MSD, Novartis Research Funding: MSD Travel, Accommodations, Expenses: Merck Serono, Amgen Su Pin Choo Honoraria: Bristol Myers Squibb, AstraZeneca Consulting or Advisory Role: Bristol Myers Squibb, AstraZeneca, Bayer, MSD Oncology, Eisai, Roche Travel, Accommodations, Expenses: Taiho Pharmaceutical, Bristol Myers Squibb Chee-Keong Toh Stock and Other Ownership Interests: Nektar Consulting or Advisory Role: Merck, Bristol Myers Squibb/Celgene, Astellas Pharma, MSD Oncology, Roche, DKSH, Natera, Eisai, Pfizer Speakers' Bureau: Ipsen, AstraZeneca, Merck, Astellas Pharma Mohamad Farid Honoraria: Bayer Consulting or Advisory Role: Bayer N. Gopalakrishna Iyer Consulting or Advisory Role: InvitroCue Patents, Royalties, Other Intellectual Property: A device and method of providing lighting during surgeries in deep and narrow cavities Inventors: N. C. Tan, W. S. Tan, M. H. Chew, H. K. Tan, P. Sunkeri, R. S. L. Lieu, F. W. L. Loke, N. G. Iyer. PCTSG2016-050231. Licensed to Vivo Surgical Pte Ltd Wan Teck Lim Consulting or Advisory Role: Roche, AstraZeneca, MSD Oncology, Novartis, Boehringer Ingelheim Research Funding: Bristol Myers Squibb Travel, Accommodations, Expenses: AstraZeneca, Taiho Pharmaceutical Daniel S. W. Tan Honoraria: Bristol Myers Squibb, Takeda, Novartis, Roche, Pfizer Consulting or Advisory Role: Novartis, Merck, Loxo, AstraZeneca, Roche, Pfizer Research Funding: Novartis, GlaxoSmithKline, AstraZeneca Travel, Accommodations, Expenses: Pfizer, Boehringer Ingelheim, Roche No other potential conflicts of interest were reported.Aaron C. Tan Honoraria: Amgen, Thermo Fisher Scientific Travel, Accommodations, Expenses: ASLAN Pharmaceuticals, Illumina Tira J. Tan Stock and Other Ownership Interests: Immunomedics Honoraria: AstraZeneca, Roche/Genentech Consulting or Advisory Role: AstraZeneca, Lilly, Pfizer, DKSH, Novartis Speakers' Bureau: Novartis Research Funding: Bayer, Novartis, AstraZeneca, Odonate Therapeutics, Synthon Travel, Accommodations, Expenses: AstraZeneca, Eisai Matthew C. H. Ng Honoraria: MSD Oncology, Taiho Pharmaceutical, ASLAN Pharmaceuticals, Lilly Consulting or Advisory Role: MSD Oncology, Bristol Myers Squibb, Novartis, Merck Speakers' Bureau: Lilly Research Funding: ASLAN Pharmaceuticals Travel, Accommodations, Expenses: MSD Oncology, Taiho Pharmaceutical, Bristol Myers Squibb David W. M. Tai Honoraria: Bristol Myers Squibb, Eisai Consulting or Advisory Role: Bristol Myers Squibb, Eisai Speakers' Bureau: Ipsen, Bristol Myers Squibb, Eisai, Roche Research Funding: Bristol-Myers Squibb, Sirtex Medical, Novartis. Justina Y. C. Lam Honoraria: AstraZeneca Consulting or Advisory Role: AstraZeneca Research Funding: Bayer, Merus, Bristol Myers Squibb Travel, Accommodations, Expenses: Lilly Bien-Soo Tan Research Funding: Boston Scientific Rebecca Alexandra Dent Honoraria: Roche/Genentech, AstraZeneca, Pfizer, MSD Consulting or Advisory Role: Roche, Pfizer, Merck, Eisai, AstraZeneca, Novartis Travel, Accommodations, Expenses: Roche, Pfizer, Amgen, Merck Yoon-Sim Yap Honoraria: Novartis, Lilly, Pfizer, AstraZeneca, Eisai, MSD, Inivata Consulting or Advisory Role: Novartis, Lilly, Pfizer, AstraZeneca, Eisai, MSD, Inivata Travel, Accommodations, Expenses: Pfizer, AstraZeneca, Eisai, Lilly, Roche, Novartis Iain B. H. Tan Honoraria: Amgen, Roche, Merck Serono, MSD Consulting or Advisory Role: Amgen, Roche, Merck Serono, MSD, Novartis Research Funding: MSD Travel, Accommodations, Expenses: Merck Serono, Amgen Su Pin Choo Honoraria: Bristol Myers Squibb, AstraZeneca Consulting or Advisory Role: Bristol Myers Squibb, AstraZeneca, Bayer, MSD Oncology, Eisai, Roche Travel, Accommodations, Expenses: Taiho Pharmaceutical, Bristol Myers Squibb Chee-Keong Toh Stock and Other Ownership Interests: Nektar Consulting or Advisory Role: Merck, Bristol Myers Squibb/Celgene, Astellas Pharma, MSD Oncology, Roche, DKSH, Natera, Eisai, Pfizer Speakers' Bureau: Ipsen, AstraZeneca, Merck, Astellas Pharma Mohamad Farid Honoraria: Bayer Consulting or Advisory Role: Bayer N. Gopalakrishna Iyer Consulting or Advisory Role: InvitroCue Patents, Royalties, Other Intellectual Property: A device and method of providing lighting during surgeries in deep and narrow cavities Inventors: N. C. Tan, W. S. Tan, M. H. Chew, H. K. Tan, P. Sunkeri, R. S. L. Lieu, F. W. L. Loke, N. G. Iyer. PCTSG2016-050231. Licensed to Vivo Surgical Pte Ltd Wan Teck Lim Consulting or Advisory Role: Roche, AstraZeneca, MSD Oncology, Novartis, Boehringer Ingelheim Research Funding: Bristol Myers Squibb Travel, Accommodations, Expenses: AstraZeneca, Taiho Pharmaceutical Daniel S. W. Tan Honoraria: Bristol Myers Squibb, Takeda, Novartis, Roche, Pfizer Consulting or Advisory Role: Novartis, Merck, Loxo, AstraZeneca, Roche, Pfizer Research Funding: Novartis, GlaxoSmithKline, AstraZeneca Travel, Accommodations, Expenses: Pfizer, Boehringer Ingelheim, Roche No other potential conflicts of interest were reported., (© 2021 by American Society of Clinical Oncology.)

Introduction: RET rearrangements are an emerging targetable oncogenic fusion driver in NSCLC. However, the natural history of disease and activity of different classes of systemic therapy remain to be defined. Furthermore, molecular testing for RET is not yet routine, and the optimal method of testing is unclear. We present a comparative analysis of molecular profiling with fluorescence in situ hybridization (FISH) or next-generation sequencing (NGS) and treatment outcomes., Methods: This study was a retrospective analysis of patients treated at the National Cancer Centre Singapore. Baseline demographics and treatment outcomes were collected., Results: A total of 64 patients were included, with a median age of 62 years (range: 25-85), 56% were women, 77% were of Chinese ethnicity, 95% had adenocarcinoma, and 69% were never smokers. RET rearrangement was detected by FISH in 30 of 34 patients (88%), NGS in 40 of 43 patients (93%), and with discordant results in seven of 13 patients (54%) tested with both methods. Of 61 patients with stage IIIB/IV or recurrent disease, prevalence of central nervous system metastases was 31% and 92% received palliative systemic therapy. Overall survival was prolonged in patients treated with a selective RET tyrosine kinase inhibitor versus untreated patients (median 49.3 versus 15.3 mo; hazard ratio [HR]: 0.16, 95% confidence interval [CI]: 0.06-0.40, p < 0.001). However, it was not different in patients treated with immunotherapy versus untreated patients (median 37.7 versus 49.3 mo; HR: 1.30, 95% CI: 0.53-3.19, p = 0.53). Overall survival was also prolonged in patients with CCDC6-RET fusion versus those with KIF5B-RET fusion (median 113.5 versus 37.7 mo; HR: 0.12, 95% CI: 0.04-0.38, p = 0.009)., Conclusions: In RET-rearranged NSCLC, selective RET tyrosine kinase inhibitor therapy is associated with improved survival outcomes, especially in patients with CCDC6-RET fusion. However, immunotherapy has poor efficacy. NGS and FISH testing methods may also result in substantial discordance., (Copyright © 2020. Published by Elsevier Inc.)

Aim: The survival benefit of using a non-cross resistant second-line chemotherapy in the third-line setting in metastatic gastroesophageal cancer is unproven. We evaluated the utility of third-line chemotherapy in patients treated at a single institution., Methods: Between 2010 and 2014, efficacy and toxicity data of patients who received three or more lines of systemic therapies for metastatic gastroesophageal adenocarcinoma at the National Cancer Centre Singapore was retrospectively analyzed., Results: Thirty-two (6%) patients received three or more lines of chemotherapy. The median age and ECOG performance status were 59 years (36-82) and 1 (0-2), respectively. Majority of patients (88%) had tumor located in the stomach and 13 patients (41%) had diffuse histology or poorly cohesive or signet ring cells. Four (12%) patients had HER2-positive disease. Prior therapy was platinum (100%), fluoropyrimidine (97%), taxane (63%), irinotecan (28%), anthracycline (13%) and ramucirumab (3%). Third-line therapy consisted of 24 (75%) monotherapy, 6 (19%) doublet, 1 (3%) triplet chemotherapy and 1 (3%) clinical trial. Monotherapy irinotecan (44%) was most common, followed by docetaxel (19%) and paclitaxel (9%). Of 22 patients evaluable for response, there was 1 (5%) partial response, 9 (41%) stable disease. Median overall survival was 18.3 weeks (4.3-65.1). Of 30 patients evaluable for toxicities, 17 (57%) experienced at least one grade 3 or 4 toxicities., Conclusion: The benefit of using non-cross resistant second-line regimens as third-line chemotherapy was small with moderate toxicity. Newer agents such as nivolumab or TAS-102 or clinical trial may be preferred., (© 2019 John Wiley & Sons Australia, Ltd.)