Tepotinib plus osimertinib in patients with EGFR-mutated non-small-cell lung cancer with MET amplification following progression on first-line osimertinib (INSIGHT 2): a multicentre, open-label, phase 2 trial.

BACKGROUND: Patients with EGFR-mutated non-small-cell lung cancer (NSCLC) and MET amplification as a mechanism of resistance to first-line osimertinib have few treatment options. Here, we report the primary analysis of the phase 2 INSIGHT 2 study evaluating tepotinib, a highly selective MET inhibitor, combined with osimertinib in this population. METHODS: This open-label, phase 2 study was conducted at 179 academic centres and community clinics in 17 countries. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1 and advanced or metastatic EGFR-mutated NSCLC of any histology, with MET amplification by tissue biopsy fluorescence in-situ hybridisation (FISH; MET gene copy number of ≥5 or MET-to-CEP7 ratio of ≥2) or liquid biopsy next-generation sequencing (MET plasma gene copy number of ≥2·3), following progression on first-line osimertinib. Patients received oral tepotinib 500 mg plus oral osimertinib 80 mg once daily. The primary endpoint was independently assessed objective response in patients with MET amplification by central FISH treated with tepotinib plus osimertinib with at least 9 months of follow-up. Safety was analysed in patients who received at least one study drug dose. This study is registered with ClinicalTrials.gov, NCT03940703 (enrolment complete). FINDINGS: Between Feb 13, 2020, and Nov 4, 2022, 128 patients (74 [58%] female, 54 [42%] male) were enrolled and initiated tepotinib plus osimertinib. The primary activity analysis population included 98 patients with MET amplification confirmed by central FISH, previous first-line osimertinib and at least 9 months of follow-up (median 12·7 months [IQR 9·9-20·3]). The confirmed objective response rate was 50·0% (95% CI 39·7-60·3; 49 of 98 patients). The most common treatment-related grade 3 or worse adverse events were peripheral oedema (six [5%] of 128 patients), decreased appetite (five [4%]), prolonged electrocardiogram QT interval (five [4%]), and pneumonitis (four [3%]). Serious treatment-related adverse events were reported in 16 (13%) patients. Deaths of four (3%) patients were assessed as potentially related to either trial drug by the investigator due to pneumonitis (two [2%] patients), decreased platelet count (one [1%]), respiratory failure (one [1%]), and dyspnoea (one [1%]); one death was attributed to both pneumonitis and dyspnoea. INTERPRETATION: Tepotinib plus osimertinib showed promising activity and acceptable safety in patients with EGFR-mutated NSCLC and MET amplification as a mechanism of resistance to first-line osimertinib, suggesting a potential chemotherapy-sparing oral targeted therapy option that should be further investigated. FUNDING: Merck (CrossRef Funder ID: 10.13039/100009945).

Hand-foot syndrome in cancer patients on capecitabine: examining prevalence, impacts, and associated risk factors at a cancer centre in Malaysia.

INTRODUCTION: Hand-foot syndrome (HFS) significantly impacts quality of life in cancer patients undergoing capecitabine treatment. This study assessed capecitabine-associated HFS prevalence, its impacts on chemotherapy treatment, and identified risk factors in multiracial Malaysian patients. METHODS: We included adult cancer patients receiving capecitabine at Sarawak General Hospital for at least two cycles from April 1, 2021 to June 30, 2022. HFS rates, time to HFS, and proportions of HFS-related treatment modifications were determined. Characteristics between patients with and without HFS were compared and multivariable logistic regression was used to identify risk factors for all-grade HFS and grade ≥2. RESULTS: Among 369 patients, 185 (50.1%) developed HFS, with 14.6% experiencing grade ≥2 and 21.6% (40/185) underwent treatment modifications. Risk factors for all-grade HFS include older age (OR 1.03 95%CI 1.01, 1.06), prior chemotherapy (OR 2.09 95%CI 1.22, 3.58), higher capecitabine dose (OR 2.96 95%CI 1.62, 5.38), prolonged treatment (OR 1.36 95%CI 1.21, 1.51), folic acid intake (OR 3.27 95%CI 1.45, 7.35) and lower neutrophil count (OR 0.77 95%CI 0.66, 0.89). For HFS grade ≥2, older age (OR 1.04 95%CI 1.01, 1.08), female sex (OR 2.10 95%CI 1.05, 4.18), Chinese race (OR 2.10 95%CI 1.06, 4.18), and higher capecitabine dose (OR 2.62 95%CI 1.28, 5.35) are significant risk factors. Use of calcium channel blockers were associated with reduced risks of all-grade HFS (OR 0.27, 95%CI 0.12, 0.60) and grade ≥2 (OR 0.21 95%CI 0.06, 0.78). CONCLUSION: This study provides real-world data on capecitabine-induced HFS in Malaysian patients and identifies risk factors that may offer insights into its understanding and management.

Nasopharyngeal carcinoma in Sarawak : a 10-year review and update.

AIM: Nasopharyngeal carcinoma (NPC) is prevalent in certain regions, particularly Southeast Asia and Southern China. In Malaysia, it is notably frequent among the Bidayuh community. This study presents a comprehensive review of NPC cases diagnosed and treated at Sarawak General Hospital from 2010 to 2020. METHOD: A retrospective data collection was conducted using the clinical records of patients who were histopathologically diagnosed with NPC at the Otolaryngology-Head & Neck Clinic and the Radiotherapy & Oncology Clinic at Sarawak General Hospital. RESULT: The study comprised a total of 892 patients from 2010 to 2020. Males outnumbered females 3-to-1, with a mean age of 51 years (standard deviation: 13.9). The largest groups of patients were the Iban (34%) and the Bidayuh (21%), followed by the Chinese (19%) and the Malay (15%). The Bidayuh had the highest incidence rate with 81 cases per 100,000. Only 10% of the study population had a family history of NPC. The most common presentation was a neck lump (64.5%). Distant metastasis was discovered in 20% of patients. 82% of the cases were stage 3 or 4 at the time of presentation. The histological types of the 892 cases were mainly undifferentiated carcinoma (73%). Eighty-six patients developed recurrence, with 83% experiencing local recurrence, 10% developing distant metastasis, and 7% developing regional recurrence. Treatment for recurrence included nasopharyngectomy, neck dissection, and chemotherapy. CONCLUSION: The study highlights a significant incidence of NPC among the Bidayuh. Emphasis on screening and early detection is crucial for better outcomes, with lifelong follow-up recommended.

Molecular pathology quality control in Southeast Asia: Results of a multiregional quality assurance study from MASTER KEY Asia.

Tissue specimen quality assurance is a major issue of precision medicine for rare cancers. However, the laboratory standards and quality of pathological specimens prepared in Asian hospitals remain unknown. To understand the methods in Southeast Asian oncology hospitals and to clarify how pre-analytics affect the quality of formalin-fixed paraffin-embedded (FFPE) specimens, a questionnaire surveying pre-analytical procedures (Part I) was administered, quality assessment of immunohistochemistry (IHC) staining and DNA/RNA extracted from the representative FFPE specimens from each hospital (Part II) was conducted, and the quality of DNA/RNA extracted from FFPE of rare-cancer patients for genomic sequencing (Part III) was examined. Quality measurements for DNA/RNA included ΔΔCt, DV200, and cDNA yield. Six major cancer hospitals from Malaysia, Philippines, and Vietnam participated. One hospital showed unacceptable quality for the DNA/RNA assessment, but improved by revising laboratory procedures. Only 57% (n = 73) of the 128 rare-cancer patients' specimens met both DNA and RNA quality criteria for next-generation sequencing. Median DV200 was 80.7% and 64.3% for qualified and failed RNA, respectively. Median ΔΔCt was 1.25 for qualified and 4.89 for failed DNA. Longer storage period was significantly associated with poor DNA (fail to qualify ratio = 1579:321 days, p < 0.001) and RNA (fail to qualify ratio = 1070:280 days, p < 0.001). After improvement of pre-analytical factors, the qualification rate increased for hospitals A and E from 41.5% to 70.5% and 62.5% to 86%, respectively. This is the first report to elucidate the pre-analytical laboratory procedures of main Southeast Asian oncology hospitals. An external quality assessment program may improve factors associated with tumor FFPE specimen quality.

A new era of the Asian clinical research network: a report from the ATLAS international symposium.

This report summarizes the presentations and discussions in the first Asian Clinical Trials Network for Cancers (ATLAS) international symposium that was held on 24 April 2022, in Bangkok, Thailand, and hosted by the National Cancer Center Hospital (NCCH), co-hosted by the Pharmaceuticals and Medical Devices Agency (PMDA), Clinical Research Malaysia (CRM) and the Thai Society of Clinical Oncology (TSCO), and supported by Embassy of Japan in Thailand. Since 2020, the NCCH has conducted the ATLAS project to enhance research environments and infrastructures to facilitate international clinical research and cancer genomic medicine in the Asian region. The purpose of the symposium was to discuss what we can achieve under the ATLAS project, to share the latest topics and common issues in cancer research and to facilitate mutual understanding. Invitees included stakeholders from academic institutions, mainly at ATLAS collaborative sites, as well as Asian regulatory authorities. The invited speakers discussed ongoing collaborative research, regulatory perspectives to improve new drug access in Asia, the status of phase I trials in Asia, the introduction of research activities at the National Cancer Center (NCC) and the implementation of genomic medicine. As the next steps after this symposium, the ATLAS project will foster increased cooperation between investigators, regulatory authorities and other stakeholders relevant to cancer research, and establish a sustainable pan-Asian cancer research group to increase the number of clinical trials and deliver novel drugs to patients with cancer in Asia.

Oncologist-led BRCA counselling improves access to cancer genetic testing in middle-income Asian country, with no significant impact on psychosocial outcomes.

BACKGROUND: Identifying patients with BRCA mutations is clinically important to inform on the potential response to treatment and for risk management of patients and their relatives. However, traditional referral routes may not meet clinical needs, and therefore, mainstreaming cancer genetics has been shown to be effective in some high-income and high health-literacy settings. To date, no study has reported on the feasibility of mainstreaming in low-income and middle-income settings, where the service considerations and health literacy could detrimentally affect the feasibility of mainstreaming. METHODS: The Mainstreaming Genetic Counselling for Ovarian Cancer Patients (MaGiC) study is a prospective, two-arm observational study comparing oncologist-led and genetics-led counselling. This study included 790 multiethnic patients with ovarian cancer from 23 sites in Malaysia. We compared the impact of different method of delivery of genetic counselling on the uptake of genetic testing and assessed the feasibility, knowledge and satisfaction of patients with ovarian cancer. RESULTS: Oncologists were satisfied with the mainstreaming experience, with 95% indicating a desire to incorporate testing into their clinical practice. The uptake of genetic testing was similar in the mainstreaming and genetics arm (80% and 79%, respectively). Patient satisfaction was high, whereas decision conflict and psychological impact were low in both arms of the study. Notably, decisional conflict, although lower than threshold, was higher for the mainstreaming group compared with the genetics arm. Overall, 13.5% of patients had a pathogenic variant in BRCA1 or BRCA2, and there was no difference between psychosocial measures for carriers in both arms. CONCLUSION: The MaGiC study demonstrates that mainstreaming cancer genetics is feasible in low-resource and middle-resource Asian setting and increased coverage for genetic testing.

Health-related quality-of-life assessment of patients with solid tumors on immuno-oncology therapies.

Immuno-oncology therapies have been approved for various solid tumors; however, the high cost of these treatments and their potential toxicities require a thorough assessment of their risks and benefits. Collection of data directly from patients through patient-reported outcome instruments can improve the precision and reliability of adverse event detection, assess tolerability of adverse events, and provide an evaluation of health-related quality of life (HRQOL) changes from immuno-oncology therapies. There is robust development in HRQOL tools specifically for patients treated with immuno-oncology agents. This review examines the history and basic concepts of HRQOL and patient-reported outcome assessments commonly used in oncological trials, highlighting the strengths and weaknesses of current approaches when applied to immunotherapies, as well as some of the current efforts to develop tools for this field and opportunities for future research. LAY SUMMARY: Immuno-oncology (IO) therapies are costly and carry potential toxicities known as immune-related adverse events. Evaluation of health-related quality of life (HRQOL) can impact the risk-benefit assessment of IO therapies. Integration of HRQOL end points and patient-reported outcome data for IO therapies are urgently needed. Ongoing robust development of patient-reported outcome tools specific to IO therapies are currently underway and will permit the evaluation of HRQOL for IO agents. Improvement in precision and reliability of HRQOL evaluation will enhance the ultimate true value of these expensive and effective drugs.

Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer.

BACKGROUND: Osimertinib is an oral, third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations. We compared osimertinib with standard EGFR-TKIs in patients with previously untreated, EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). METHODS: In this double-blind, phase 3 trial, we randomly assigned 556 patients with previously untreated, EGFR mutation-positive (exon 19 deletion or L858R) advanced NSCLC in a 1:1 ratio to receive either osimertinib (at a dose of 80 mg once daily) or a standard EGFR-TKI (gefitinib at a dose of 250 mg once daily or erlotinib at a dose of 150 mg once daily). The primary end point was investigator-assessed progression-free survival. RESULTS: The median progression-free survival was significantly longer with osimertinib than with standard EGFR-TKIs (18.9 months vs. 10.2 months; hazard ratio for disease progression or death, 0.46; 95% confidence interval [CI], 0.37 to 0.57; P<0.001). The objective response rate was similar in the two groups: 80% with osimertinib and 76% with standard EGFR-TKIs (odds ratio, 1.27; 95% CI, 0.85 to 1.90; P=0.24). The median duration of response was 17.2 months (95% CI, 13.8 to 22.0) with osimertinib versus 8.5 months (95% CI, 7.3 to 9.8) with standard EGFR-TKIs. Data on overall survival were immature at the interim analysis (25% maturity). The survival rate at 18 months was 83% (95% CI, 78 to 87) with osimertinib and 71% (95% CI, 65 to 76) with standard EGFR-TKIs (hazard ratio for death, 0.63; 95% CI, 0.45 to 0.88; P=0.007 [nonsignificant in the interim analysis]). Adverse events of grade 3 or higher were less frequent with osimertinib than with standard EGFR-TKIs (34% vs. 45%). CONCLUSIONS: Osimertinib showed efficacy superior to that of standard EGFR-TKIs in the first-line treatment of EGFR mutation-positive advanced NSCLC, with a similar safety profile and lower rates of serious adverse events. (Funded by AstraZeneca; FLAURA ClinicalTrials.gov number, NCT02296125 .).

Management of advanced prostate cancer in a middle-income country: real-world consideration of the Advanced Prostate Cancer Consensus Conference 2017.

OBJECTIVE: To examine the results of the Malaysian Advanced Prostate Cancer Consensus Conference (MyAPCCC) 2018, held for assessing the generalizability of consensus reached at the Advanced Prostate Cancer Consensus Conference (APCCC 2017) to Malaysia, a middle-income country. METHODS: Six key sections were chosen: (1) high-risk localized and locally advanced prostate cancer, (2) oligometastatic prostate cancer, (3) castration-naïve prostate cancer, (4) castrate resistant prostate cancer, (5) use of osteoclast-targeted therapy and (6) global access to prostate cancer drugs. There were 101 consensus questions, consisting of 91 questions from APCCC 2017 and 10 new questions from MyAPCCC 2018, selected and modified by the steering committee; of which, 23 questions were assessed in both ideal world and real-world settings. A panel of 22 experts, comprising of 11 urologists and 11 oncologists, voted on 101 predefined questions anonymously. Final voting results were compared with the APCCC 2017 outcomes. RESULTS: Most voting results from the MyAPCCC 2018 were consistent with the APCCC 2017 outcomes. No consensus was achieved for controversial topics with little level I evidence, such as management of oligometastatic disease. No consensus was reached on using high-cost drugs in castration-naïve or castration-resistant metastatic prostate cancer in real-world settings. All panellists recommended using generic drugs when available. CONCLUSIONS: The MyAPCCC 2018 voting results reflect the management of advanced prostate cancer in a middle-income country in a real-world setting. These results may serve as a guide for local clinical practices and highlight the financial challenges in modern healthcare.

A 4-year review of surgical and oncological outcomes of endoscopic endonasal transpterygoid nasopharyngectomy in salvaging locally recurrent nasopharyngeal carcinoma.

PURPOSE: To study the surgical and oncological outcomes of endoscopic endonasal transpterygoid nasopharyngectomy (EETN) in salvaging locally recurrent nasopharyngeal carcinoma (NPC). METHOD: This was a retrospective clinical record review study carried out at a tertiary centre from June 2013 until May 2017. A total of 55 locally recurrent NPC patients (rT1-rT4) underwent EETN performed by single skull base surgeon with curative intention with postoperative adjuvant chemotherapy but without postoperative radiotherapy. RESULTS: There were 44 (80.0%) males and 11 (20.0%) females, with mean age of 52.5 years. The mean operating time was 180 min (range 150-280 min). 85% (47/55) of patients achieved en bloc tumour resection. 93% (51/55) of patients obtained negative microscopic margin based on postoperative histopathological evaluation. Intraoperatively, one (1.8%) patient had internal carotid artery injury which was successfully stented and had recovered fully without neurological deficit. There were no major postoperative complications reported. During a mean follow-up period of 18-month (range 12-48 months) postsurgery, five patients (9.1%) had residual or recurrence at the primary site. All five patients underwent re-surgery. One patient at rT3 passed away 6 months after re-surgery due to distant metastasis complicated with septicaemia. The 1-year local disease-free rate was 93% and the 1-year overall survival rate was 98%. CONCLUSIONS: EETN is emerging treatment options for locally recurrent NPC, with relatively low morbidity and encouraging short-term outcome. Long-term outcome is yet to be determined with longer follow-up and bigger cohort study. However, a successful surgical outcome required a very experienced team and highly specialised equipment.

Barriers And Challenges Of Multidisciplinary Teams In Oncology Management: A Scoping Review Protocol.

INTRODUCTION: Multidisciplinary teams (MDTs) are integral to oncology management, involving specialised healthcare professionals who collaborate to develop individualised treatment plans for patients. However, as cancer care grows more complex, MDTs must continually adapt to better address patient needs. This scoping review will explore barriers and challenges MDTs have encountered in the past decade; and propose strategies for optimising their utilisation to overcome these obstacles and improve patient care. METHODS AND ANALYSIS: The scoping review will follow Arksey and O'Malley's framework and begin with a literature search using keywords in electronic databases such as PubMed/MEDLINE, Scopus and PsychINFO, covering the period from January 2013 to December 2022 and limited to English language publications. Four independent reviewers will screen titles and abstracts based on predefined inclusion criteria, followed by full-text review of selected titles. Relevant references cited in the publications will also be examined. A Preferred Reporting Items for Systematic reviews and Meta-Analyses flow diagram will be utilised to illustrate the methodology. Data from selected publications will be extracted, analysed, and categorised for further analysis. ETHICS AND DISSEMINATION: The results of the scoping review will provide a comprehensive overview of the barriers and challenges encountered by oncology MDTs over the past decade. These findings will contribute to the existing literature and provide insights into areas that require improvement in the functioning of MDTs in oncology management. The results will be disseminated through publication in a scientific journal, which will help to share the findings with the wider healthcare community and facilitate further research and discussion in this field. TRIAL REGISTRATION DETAILS: The protocol for this scoping review is registered with Open Science Framework, available at DOI 10.17605/OSF.IO/R3Y8U.

Identification of phenomic data in the pathogenesis of cancers of the gastrointestinal (GI) tract in the UK biobank.

Gastrointestinal (GI) cancers account for a significant incidence and mortality rates of cancers globally. Utilization of a phenomic data approach allows researchers to reveal the mechanisms and molecular pathogenesis of these conditions. We aimed to investigate the association between the phenomic features and GI cancers in a large cohort study. We included 502,369 subjects aged 37-73 years in the UK Biobank recruited since 2006, followed until the date of the first cancer diagnosis, date of death, or the end of follow-up on December 31st, 2016, whichever occurred first. Socio-demographic factors, blood chemistry, anthropometric measurements and lifestyle factors of participants collected at baseline assessment were analysed. Unvariable and multivariable logistic regression were conducted to determine the significant risk factors for the outcomes of interest, based on the odds ratio (OR) and 95% confidence intervals (CI). The analysis included a total of 441,141 participants, of which 7952 (1.8%) were incident GI cancer cases and 433,189 were healthy controls. A marker, cystatin C was associated with total and each gastrointestinal cancer (adjusted OR 2.43; 95% CI 2.23-2.64). In this cohort, compared to Asians, the Whites appeared to have a higher risk of developing gastrointestinal cancers. Several other factors were associated with distinct GI cancers. Cystatin C and race appear to be important features in GI cancers, suggesting some overlap in the molecular pathogenesis of GI cancers. Given the small proportion of Asians within the UK Biobank, the association between race and GI cancers requires further confirmation.

Gaps in cancer care in a multi-ethnic population in Sarawak, Borneo: A central referral centre study.

BACKGROUND: The state of Sarawak on the island of Borneo in East Malaysia, in working towards developing and strengthening cancer services through a holistic patient-centred approach, must focus on the comprehensive needs of cancer patients by taking into account the psycho-social, cultural and spiritual aspects of Sarawak's multi-ethnic, multi-cultural population. METHODS: A 42-item survey questionnaire was developed and validated with a total of 443 patients. The perceived importance of information provided and level of patient satisfaction were assessed with a 5-point Likert scale in 10 domains (Diagnosis, Surgery, Radiotherapy, Systemic therapy, Clinical trials, Pain management, Treatment monitoring, Psychosocial support, Sexual care and fertility issues, and Financial support). A Spearman's rank correlation test was applied to determine the correlation between response in both item and domain categories for perceived importance and satisfaction. RESULTS: Overall, patients were more satisfied with information related to cancer diagnosis, treatment and surgery but less satisfied with information pertaining to sexual aspects of care and family planning, psycho-social support and financial support. The majority of patients were satisfied with the level of treatment-related information received but preferred the information to be delivered in more easily comprehendible formats. Sexual aspects of care and family planning, psychosocial support and treatment monitoring post-discharge were perceived as important but seldom addressed by health care professionals due to lack of professional counsellors, social workers and clinical nurse specialists. Many patients face financial toxicity following a cancer diagnosis, particularly when diagnosed with advanced cancer requiring complex multi-modality treatment. CONCLUSION: Cancer patients in Sarawak have various unmet information needs. Written information and educational videos in local indigenous languages may be more suitable for Sarawak's multi-ethnic population. Sexual aspects of care and family planning are challenging but essential topics to discuss, in particular due to the high prevalence of breast and cervical cancer amongst young women of reproductive age in Sarawak. Financial assessment and information on support services offered by government and non-government organisations should be provided to eligible patients. A holistic needs assessment of each patient at time of diagnosis and support through their cancer journey requires a multi-disciplinary team of medical, nursing and allied health professionals including clinical nurse specialists, pharmacists, counsellors, physiotherapists, occupational therapists, speech and language therapists, dieticians and social workers.

Subcutaneous Versus Intravenous Amivantamab, Both in Combination With Lazertinib, in Refractory Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer: Primary Results From the Phase III PALOMA-3 Study.

PURPOSE: Phase III studies of intravenous amivantamab demonstrated efficacy across epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC). A subcutaneous formulation could improve tolerability and reduce administration time while maintaining efficacy. PATIENTS AND METHODS: Patients with EGFR-mutated advanced NSCLC who progressed after osimertinib and platinum-based chemotherapy were randomly assigned 1:1 to receive subcutaneous or intravenous amivantamab, both combined with lazertinib. Coprimary pharmacokinetic noninferiority end points were trough concentrations (Ctrough; on cycle-2-day-1 or cycle-4-day-1) and cycle-2 area under the curve (AUCD1-D15). Key secondary end points were objective response rate (ORR) and progression-free survival (PFS). Overall survival (OS) was a predefined exploratory end point. RESULTS: Overall, 418 patients underwent random assignment (subcutaneous group, n = 206; intravenous group, n = 212). Geometric mean ratios of Ctrough for subcutaneous to intravenous amivantamab were 1.15 (90% CI, 1.04 to 1.26) at cycle-2-day-1 and 1.42 (90% CI, 1.27 to 1.61) at cycle-4-day-1; the cycle-2 AUCD1-D15 was 1.03 (90% CI, 0.98 to 1.09). ORR was 30% in the subcutaneous and 33% in the intravenous group; median PFS was 6.1 and 4.3 months, respectively. OS was significantly longer in the subcutaneous versus intravenous group (hazard ratio for death, 0.62; 95% CI, 0.42 to 0.92; nominal P = .02). Fewer patients in the subcutaneous group experienced infusion-related reactions (IRRs; 13% v 66%) and venous thromboembolism (9% v 14%) versus the intravenous group. Median administration time for the first infusion was reduced to 4.8 minutes (range, 0-18) for subcutaneous amivantamab and to 5 hours (range, 0.2-9.9) for intravenous amivantamab. During cycle-1-day-1, 85% and 52% of patients in the subcutaneous and intravenous groups, respectively, considered treatment convenient; the end-of-treatment rates were 85% and 35%, respectively. CONCLUSION: Subcutaneous amivantamab-lazertinib demonstrated noninferiority to intravenous amivantamab-lazertinib, offering a consistent safety profile with reduced IRRs, increased convenience, and prolonged survival.

Correlation of aldo-ketoreductase (AKR) 1C3 genetic variant with doxorubicin pharmacodynamics in Asian breast cancer patients.

AIMS: Aldo-ketoreductases have been implicated in the metabolism of doxorubicin. We sought to assess the influence of AKR1C3 genetic variants on doxorubicin metabolism. METHODS: We sequenced AKR1C3 exon 5 and genotyped seven functional single nucleotide polymorphisms in CBR3, ABCB1 and SLC22A16 involved in doxorubicin pharmacology in 151 Asian breast cancer patients treated with doxorubicin-containing chemotherapy, and correlated these genotypes with doxorubicin pharmacokinetics and pharmacodynamics. RESULTS: Two previously reported AKR1C3 intronic variants, IVS4-212 C>G and IVS4+218 G>A, were detected. The AKR1C3 IVS4-212 GG genotype was associated with significantly lower cycle 1 day 15 leucocyte (mean leucocytes 2.49 ± 1.57 × 10(9) vs. 3.85 ± 3.42 × 10(9) l(-1) , P = 0.007) and neutrophil counts (mean neutrophils 0.70 ± 1.01 × 10(9) vs. 1.56 ± 2.80 × 10(9) l(-1) , P = 0.008) and significant improvement of progression-free survival [PFS, mean PFS 49.0 (95% confidence interval 42.2-55.8) vs. 31.0 (95% confidence interval 20.7-41.2) months, P = 0.017] and overall survival [OS; mean OS 64.4 (95% confidence interval 58.3-70.5) vs. 46.3 (95% confidence interval 35.1-57.5) months, P = 0.006] compared with those carrying at least one C allele. There was no significant association between AKR1C3 IVS4-212 C>G and doxorubicin pharmacokinetics. Of the other seven single nucleotide polymorphisms genotyped, CBR3 G11A correlated with doxorubicinol area under the concentration-time curve and OS, ABCB1 G2677T/A correlated with doxorubicin clearance and platelet toxicity, while ABCB1 IVS26+59 T>G correlated with OS. The AKR1C3 IVS4-212 C

Early phase oncology clinical trials in Malaysia: current status and future perspectives.

Historically, the majority of oncology clinical trials are conducted in Western Europe and North America. Globalization of drug development has resulted in sponsors shifting their focus to the Asia-Pacific region. In Malaysia, implementation of various government policies to promote clinical trials has been initiated over a decade ago and includes the establishment of Clinical Research Malaysia, which functions as a facilitator and enabler of industry-sponsored clinical trials on a nationwide basis. Although oncology clinical trials in Malaysia have seen promising growth, there are still only a limited number of early phase oncology studies being conducted. Hence, the Phase 1 Realization Project was initiated to develop Malaysia's early phase clinical trial capabilities. In addition, the adaptation of good practices from other countries contribute to the effective implementation of existing initiatives to drive progress in the development of early phase drug development set up in Malaysia. Furthermore, holistic approaches with emphasis in training and education, infrastructure capacities, strategic alliances, reinforcement of upstream activities in the value chain of drug development, enhanced patient advocacy, coupled with continued commitment from policy makers are imperative in nurturing a resilient clinical research ecosystem in Malaysia.

Development and validation of Join Clinical Trial Questionnaire (JoinCT).

AIM: Participant recruitment has always been a major challenge in clinical trials. This study aimed to develop and validate the Join Clinical Trial Questionnaire (JoinCT), exploring the willingness to join a clinical trial and associated factors in patients. METHODS: This questionnaire development study involved four phases: (i) exploring and understanding the subject matter, (ii) questionnaire development, (iii) content validity testing, and lastly, (iv) field-testing of the questionnaire. For the field-testing phase, a cross-sectional self-administered survey of JoinCT was conducted among cancer patients with various socio-demographic backgrounds and medical conditions. Besides content validity, Cronbach's alpha was used to evaluate the internal consistency of domains, and confirmatory factor analysis was used to evaluate the model fit of the JoinCT framework. RESULTS: A total of 389 respondents participated in the survey. Based on the results obtained from a field data collection phase, JoinCT consisted of four independent variables domains, namely "knowledge", "perception of benefits", "perception of risks", and "confidence". The only dependent variable was the willingness to participate in a clinical trial. The minimum Cronbach's alpha was 0.937, and the model fit for the overall framework of JoinCT is also excellent with Comparative Fit Index (> 0.90), root mean square error approximation (< 0.08), and Standardized Root Mean Square Residual (< 0.08). CONCLUSIONS: The Join Clinical Trial Questionnaire (JoinCT) was successfully validated with excellent reliability and validity, and a good model fit. The main factors that contribute to willingness to participate in clinical trials are knowledge, perception of benefits, perception of risks, and confidence.

Peripheral transbronchial needle aspiration-guided pinpoint cryobiopsy of lung nodule without bronchus sign: A case report.

Peripheral transbronchial needle aspiration (pTBNA) allows the access of pulmonary nodules without bronchus sign but is limited to cytological examination. A 39-year-old man with left parotid carcinoma presented with an incidental lung nodule. Target localisation was performed with manual airway mapping, virtual bronchoscopic navigation, and pTBNA. Direct target validation using radial endobronchial ultrasound (rEBUS) was performed through the puncture defect. Targeted pinpoint biopsy with a 1.1 mm cryoprobe through the pTBNA puncture defect confirmed metastatic adenoid cystic carcinoma. Guided pTBNA with rEBUS validation followed by cryobiopsy of lung nodules without bronchus sign is potentially feasible for histological and molecular analyses.

International Collaboration on Palliative Care Development Between ASCO and the Land of Hornbills.

PURPOSE: Palliative care in Sarawak is mainly provided by health care professionals with limited formal training in palliative care. Therefore, in 2020, collaborative work between Sarawak General Hospital, University Malaysia Sarawak, and ASCO began. This study reports on the outcome of this collaboration. METHODS: The collaboration was initiated with the first ASCO Palliative Care e-course, Train the Trainer program, International Development and Education Award-Palliative Care and translation of ASCO Palliative Care Interdisciplinary Curriculum resources. RESULTS: This collaboration has resulted in the change of practice of palliative care among the oncology team of Sarawak General Hospital. CONCLUSION: It encourages more timely palliative care referrals to ensure that patients with complex physical, psychosocial, and spiritual needs have the necessary input and support from the palliative care team throughout the course of patients' illnesses.

Real-world clinical practice and outcomes in treating stage III non-small cell lung cancer: KINDLE-Asia subset.

Introduction: Stage III non-small cell lung cancer (NSCLC) is a heterogeneous disease requiring multimodal treatment approaches. KINDLE-Asia, as part of a real world global study, evaluated treatment patterns and associated survival outcomes in stage III NSCLC in Asia. Methods: Retrospective data from 57 centers in patients with stage III NSCLC diagnosed between January 2013 and December 2017 were analyzed. Median progression free survival (mPFS) and median overall survival (mOS) estimates with two sided 95% confidence interval (CI) were determined by applying the Kaplan-Meier survival analysis. Results: Of the total 1874 patients (median age: 63.0 years [24 to 92]) enrolled in the Asia subset, 74.8% were men, 54.7% had stage IIIA disease, 55.7% had adenocarcinoma, 34.3% had epidermal growth factor receptor mutations (EGFRm) and 50.3% had programmed death-ligand 1 (PD-L1) expression (i.e. PD-L1 ≥1%). Of the 31 treatment approaches as initial therapy, concurrent chemoradiotherapy (CRT) was the most frequent (29.3%), followed by chemotherapy (14.8%), sequential CRT (9.5%), and radiotherapy (8.5%). Targeted therapy alone was used in 81 patients of the overall population. For the Asia cohort, the mPFS and mOS were 12.8 months (95% CI, 12.2-13.7) and 42.3 months (95% CI, 38.1-46.8), respectively. Stage IIIA disease, Eastern Cooperative Oncology Group ≤1, age ≤65 years, adenocarcinoma histology and surgery/concurrent CRT as initial therapy correlated with better mOS (p < 0.05). Conclusions: The results demonstrate diverse treatment patterns and survival outcomes in the Asian region. The high prevalence of EGFRm and PD-L1 expression in stage III NSCLC in Asia suggests the need for expanding access to molecular testing for guiding treatment strategies with tyrosine kinase inhibitors and immunotherapies in this region.