Three new Pan-Asian-adapted guidelines at ESMO Asia Congress

At the ESMO Asia Congress 2024 (Singapore, 6-8 December), a special session offers the chance to reflect on how the management of patients with biliary tract cancers, oncogene-addicted metastatic non-small cell lung cancer (NSCLC) and epithelial ovarian cancer has evolved recently, and how to tailor the ESMO Clinical Practice Guidelines to local contexts in Asia. Discussions are made under the umbrella of the ESMO Pan-Asian Guidelines Adaptation (PAGA) project, started in 2017, which involves ten oncology societies from Asia for the development of specific Pan-Asian-adapted guidelines.

On advanced biliary tract cancer

Despite some tumours of the biliary tract are relatively rare globally, their incidence in Asia is higher compared to other regions due to prevalence of risk factors, including specific pathogens and viral hepatitis infections (Cancer Manag Res. 2019;11:2623-2642). Published in August on ESMO Open, the Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with biliary tract cancer, whose development has been coordinated by ESMO and the Taiwan Oncology Society (TOS), highlight a paradigm shift in the management of this heterogeneous group of malignancies (ESMO Open. 2024 Aug;9(8):103647). “The first-line standard of care has been changed from simple, doublet chemotherapy, gemcitabine plus cisplatin (GemCis) to first-line GemCis-based triplets combining with either anti-PD-1/PD-L1 immune checkpoint inhibitor (durvalumab or pembrolizumab) or oral third-generation fluoropyrimidine S-1, followed by biomarker-driven second-line therapy, including mutant IDH1 inhibitor, FGFR2 inhibitors for FGFR2 fusion or rearrangement intrahepatic cholangiocarcinoma (iCCA), and agnostically approved agents targeting molecular alterations,” clarifies the first author of the paper Dr Li-Tzong Chen, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Compared to the parent ESMO Clinical Practice Guideline on biliary tract cancer published in 2023 (Ann Oncol. 2023 Feb;34(2):127-140), two new recommendations were included in the Pan-Asian adaptation - based on recent evidence from research (Lancet Oncol. 2022;23(10):1261- 1273; JCO Precis Oncol. 2022;6:e2200003) supporting the use of selpercatinib in patients whose tumours have RET fusions and who have progressed on or are intolerant to prior treatment, and pembrolizumab in those with TMB-H status who have progressed on or are intolerant to prior non-immune checkpoint inhibitor containing treatment.

On oncogene-addicted metastatic NSCLC

Biomarker testing is essential to identify subgroups of NSCLC with oncogenic drivers that can be therapeutically targeted, and different distributions of some molecular patterns have been demonstrated in the Asian population compared to the Western population (Biomark Res. 2024 Feb 12;12(1):24; Oncotarget. 2021 Mar 16;12(6):578-588). For instance, a higher rate of targetable molecular alterations has been reported in Asian patients with lung adenocarcinoma, and a high incidence of EGFR mutation in squamous-cell carcinoma has been observed in specific Asian regions, including India, Japan and China. “Given the high prevalence in this population, numerous clinical trials focusing solely on Asian patients with EGFR mutations have been conducted leading to some targeted agents to be approved exclusively for Asian markets,” notes Prof. Sehoon H. Lee from the Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, who is the project leader of the Pan-Asian adaptation of the ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with oncogene-addicted metastatic NSCLC, coordinated by ESMO and the Korean Society of Medical Oncology (KSMO) (Ann Oncol 2023; 34(4): 339-357). Published in January 2023, the parent ESMO guidelines were reviewed against the latest evidence from research and reflect a rapidly changing scenario in lung cancer management. “Recently, numerous phase 3 clinical trials and other pivotal studies have been published such as the MARIPOSA (N Engl J Med. 2024 Oct 24;391(16):1486-1498) and the MARIPOSA-2 (Ann Oncol. 2024 Jan;35(1):77-90), so their results have been incorporated into our work, leading to some recommendations to be updated, amended or deleted,” highlights Lee. The Pan-Asian adapted ESMO Clinical Practice Guidelines on oncogene-addicted metastatic NSCLC, have recently been published on ESMO Open (ESMO Open. 2024 Nov 29;9(12):103996)

On epithelial ovarian cancer

Ovarian cancer is the second most lethal gynaecological malignancy worldwide after cervical cancer, and the first in developed countries, with high rates in Asia (Globocan 2022). Compared to the parent ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up of newly diagnosed and relapsed epithelial ovarian cancer (Ann Oncol. 2023 Oct;34(10):833-848), the Pan-Asian recommendations for this heterogenous group of malignancies, which will be published on ESMO Open in early 2025, have been tailored on regional discrepancies in terms of clinical practice. “For instance, the availability of an expert gynecological pathologist is limited throughout Asia, and it is acceptable that a general onco-pathologist can effectively diagnose ovarian cancer, even in difficult cases,” highlights Dr Shona Nag, Medical Oncology Department, Sahyadri Superspeciality Hospital, Hadapsar, Pune, India, who authored the paper. “Asian experts agreed on restricting germline or somatic BRCA testing at diagnosis to all high grade non-mucinous ovarian cancers. Since country-specific resources may not allow simultaneous germline BRCA and homologous recombination deficiency (HRD) testing, sequential testing is acceptable, with a priority for germline.”
The availability of some anticancer agents, including PARP inhibitors, differs widely between various regions of Asia. “According to scientific evidence, Asian experts felt that for HRD negative ovarian cancer the use of PARP inhibitors did not substantially improve progression-free survival and could be considered, rather than recommended,” adds Nag. “Other treatments were also reviewed. For instance, efficacy data on mirvetuximab soravtansine became available after the parent ESMO guidelines were published (N Engl J Med 2023;389:2162-2174), so this option was included in our work.”

Discrepancies across Asia

A substantial part of the three new Pan-Asian-adapted Guidelines is also dedicated to the analysis of the current regulatory and reimbursement frameworks across the ten different Asian countries represented in the PAGA project, that may limit applicability of the ESMO guidelines.
“Inequalities in accessing new cancer diagnostic technology and therapeutic agents, such as next generation sequencing, and molecular targeting agents and immune checkpoint inhibitors are common among Pan-Asian countries,” confirms Chen. “Clinical practice in Asia is mostly health insurance reimbursement-guided, therefore adapting international practice guidelines based on universal health coverage, patients’ insurance status and local practice experience or clinical trial results seems inevitable.”