CONFERENCE UPDATES: WCLC 2021
A milestone in biomarker testing and therapies for lung cancer
With advancement in biomarker-driven treatment and targeted therapies for lung cancer, novel strategies are employed to optimize personalized regimens for different subtypes of lung cancer.1 To keep track of the evolving lung cancer management, a symposium regarding biomarker and treatment landscape for non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) was held at the World Conference on Lung Cancer 2021.1
Dr. David R. Gandara, MD, Director of Thoracic Oncology Program at the University of California Davis Comprehensive Cancer Center of the United States (US), started by introducing the 2 newly identified biomarkers, namely Kirsten rat sarcoma virus (KRAS) glycine 12 to cysteine (G12C) and epidermal growth factor receptor (EGFR) exon 20, for NSCLC.1 He indicated that approximately 40% of NSCLC patients contained actionable oncogenic drivers, of which, KRAS G12C mutation had shown high prevalence in ever-smokers, regardless of the clinical characteristics.1 All patients with advanced non-squamous NSCLC were recommended to undergo broad molecular testing according to the National Comprehensive Cancer Network (NCCN) guidelines, though the real-world biomarker examination rates remained suboptimal.1 “An oncologist armed with the information on biomarker testing will be more capable of determining the best therapy for patients,” said Dr. Gandara. Apart from tissue biopsy, a variety of liquid biopsy platforms have been established for routine tissue-based diagnosis and identification of acquired resistance mechanisms.1 Dr. Gandara added that liquid biopsy was suggested by the International Association for the Study of Lung Cancer (IASLC) for molecular testing of NSCLC patients, offering an alternative in the event of insufficient tissue biopsy specimens, also providing a dynamic assessment to guide treatment decisions.1
Patients with KRAS G12C-mutated NSCLC were characterized by poor progression-free survival (PFS) and overall survival (OS) outcomes in clinical trials.1 Dr. Alexander I. Spira, MD, PhD, FACP, Site Research Leader and Co-director of Clinical Research Program in Virginia Cancer Specialists Research Institute of the US, shared the findings of a newly approved KRASG12C inhibitor from recent studies.1 Patients with advanced or metastatic NSCLC receiving sotorasib, a first-in-class oral KRASG12C inhibitor, demonstrated rapid, deep and durable responses in the phase 2 single-arm CodeBreaK 100 trial.1 He highlighted that an objective response rate (ORR) occurred in 37.1% of participants (95% CI: 28.6-46.2), while the disease control rate (DCR) was 80.6% (95% CI: 72.6-87.2).1 “One of the notable things is that patients who were heavily pretreated with 3 prior lines of therapy achieved an ORR at 39.3%,” said Dr. Spira. He stated that response to sotorasib and survival outcomes were observed across the patient subgroups, including NSCLC patients with stable, previously treated brain metastases, and a favorable benefit-risk profile was performed with improved dyspnea symptoms during sotorasib treatment.1 Dr. Spira mentioned that the CodeBreaK 101 trial which included 12 different combination treatments with sotorasib has been underway.1
SCLC is an aggressive neuroendocrine cancer with poor prognosis and scanty treatment options.1 Dr. Afshin Dowlati, MD, Director of the Center for Cancer Drug Development in the University Hospitals Seidman Cancer Center and Case Western Reserve University of the US, introduced delta-like ligand 3 (DLL3) as a compelling therapeutic target in SCLC.1 DLL3 was highly expressed on the surface of neuroendocrine tumors in 85% of SCLC patients, regardless of stage.1 Dr. Dowlati illustrated that the bispecific T-cell engager (BiTE), an immune-oncology platform, utilized patients’ T-cells and SCLC cells to induce T-cell proliferation and serial lysis, followed by the apoptosis of tumor cells.1 Tarlatamab (AMG 757), adopting the BiTE technology, was investigated in the first-in-human dose exploration study in relapsed/refractory (R/R) SCLC.1 “In this study, it is interesting to us that the median duration of response (DOR) was 8.7 months, which is significantly longer than 3-4 months in other systemic therapies tried in the second-line settings,” said Dr. Dowlati. He elaborated that a feasible safety profile has been shown with tarlatamab and the confirmed partial response was appeared in 20% of patients according to this interim analysis of the ongoing phase 1 study.1 Dr. Dowlati highlighted that tarlatamab in combination with programmed cell death protein-1 (PD-1) in progressive and recurrent SCLC would be explored in upcoming clinical trials.1
To conclude, the advancement of biomarker testing and targeted therapies in recent years has expanded the treatment options, enabling precision medicine for lung cancer patients.1 With progressive clinical trials regarding the combinations of diversified therapies and agents for different types of lung cancer, it is anticipated that more novel therapies will be available for optimizing patient outcomes.1
- Gandara DR, Spira AI, Dowlati A. Advancing the Lung Cancer Landscape With Novel Strategies. Presented at World Conference on Lung Cancer 2021; September 9, 2021.
Sketching the roadmap for Asian lung cancer management: Expert consensus on lung cancer screening practices in Asian populations
Lung cancer (LC) is regarded as the most lethal form of cancer in Asia.1 In 2020, the World Health Organization (WHO) ’s Global Cancer Observatory (GLOBOCAN) estimated that 60% of global LC cases and 62% of global LC-related mortality were from Asian countries.1
Fixed-duration immunotherapy demonstrates comparable survival benefits in advanced NSCLC
Immune checkpoint inhibitor (ICI)-based treatments are one of the front-line options for patients with advanced non-small cell lung cancer (NSCLC).1 However, no optimal duration has been defined.1 At the ASCO 2023 Annual Meeting, Dr. Lova Sun from the University of Pennsylvania, the United States (US), presented the results of a US study that investigated the clinical practice patterns surrounding ICI treatment discontinuation at 2 years.1 Furthermore, the association between the duration of therapy with overall survival (OS) was evaluated by comparing patients who received ICIs for 2 years with those who had received ICIs beyond 2 years.1
Perioperative durvalumab plus neoadjuvant chemotherapy shows benefits in resectable NSCLC
Although surgery remains the first-line treatment for patients with early-stage resectable non-small-cell lung cancer (NSCLC), recent evidence has shown that the incorporation of immunotherapy with immune checkpoint inhibitors, such as programmed cell death-1 (PD-1) or programmed cell death ligand-1 (PD-L1), demonstrated benefits in the perioperative settings.1 It is believed that the enhanced perioperative regimens, by combining the benefits of neoadjuvant and adjuvant immunotherapy, could further improve patients’ long-term clinical outcomes.1
Adjuvant osimertinib and multidisciplinary-team approach in early-stage NSCLC management: A local case sharing
Non-small cell lung cancer (NSCLC) accounts for 85%of all types of lung cancer and is the most common cancer in Hong Kong with a total of 5,575 cases in 2019.1,2 Approximately 30% of NSCLC patients are diagnosed as early stage, and surgical resection is the preferred treatment option for possibly co
Pembrolizumab shows meaningful improvement in DFS as adjuvant therapy for stage IB-IIIA NSCLC
In the PEARLS/KEYNOTE-091 study, a randomized, triple-blinded phase 3 trial, pembrolizumab demonstrated an improved disease-free survival (DFS) as adjuvant therapy in patients with completely resected stage IB-IIIA non-small cell lung cancer (NSCLC) vs. placebo.1
Using adjuvant osimertinib to treat resected EGFR mutationpositive NSCLC in early stages: A local case sharing
Accounted for 15.4% of new cancer cases in 2018, lung cancer is one of the most common cancers in Hong Kong, with around 30% of patients having resectable non-small cell lung cancer (NSCLC).1,2 While adjuvant chemotherapy is the current postoperative standard of care, this treatment could only reduce the risk of disease recurrence or death by 16%.2 Recently, the ADAURA trial demonstrated that osimertinib, when utilized as an adjuvant therapy with or without chemotherapy, could prolong the disease-free survival (DFS) of patients with resected stage IB to IIIA epidermal growth factor receptor (EGFR) mutation positive NSCLC.2 In a recent interview with Omnihealth Practice, Dr. Tsang, Wai-Kong Maverick, shared a local patient case with resected stage IB EGFR mutation-positive lung adenocarcinoma who was well-tolerated to the postoperative adjuvant osimertinib without chemotherapy for 10 months.
Adopting durvalumab consolidation therapy: A breakthrough for non-small cell lung cancer treatment
Despite recent advances in oncology, drug resistance and disease relapse have remained a significant unmet need among non-small cell lung cancer (NSCLC). Recently, the development of novel therapeutics including tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) have made multiple breakthroughs in the treatment of NSCLC. In a virtual meeting and clinical debate, “Durvalumab in EGFRm Stage III NSCLC – To Offer or Not to Offer?”, Dr. Victor Lee summarized the key studies of NSCLC treatments, including the phase 3 PACIFIC trial of an anti-programmed cell death receptor ligand 1 (PD-L1) drug, durvalumab. Dr. Oscar Chan and Dr. Jonathan Nyaw then discussed the applications and other considerations of the durvalumab regimen among stage 3 Epidermal Growth Factor Receptor mutated (EGFRm) NSCLC patients in the clinical setting.
Neoadjuvant nivolumab plus chemotherapy shows long-term survival in stage IIIA NSCLC patients: NADIM study
Neoadjuvant chemoimmunotherapy has been shown to be highly effective in non-small-cell lung cancer (NSCLC) at the resectable stage IlIA.1 More than a third of NSCLC patients have stage Ill disease on diagnosis.2 NADIM study is an open-label, multicenter, single-arm phase 2 trial targeting patients with histologically or cytologically documented stage IIIA NSCLC, who were deemed locally to be surgically resectable by a multidisciplinary clinical team and with the Eastern Cooperative Oncology Group (ECG) performance status of O or 1.1 Patients received neoadjuvant treatment with intravenous paclitaxel (200mg/m2) and carboplatin (area under curve 6; 6mg/mL per minute) plus nivolumab (360mg) on day 1 of each 21-day cycle, for 3 cycles before surgical resection; then followed by the adjuvant intravenous nivolumab monotherapy for 1 year (240mg every 2 weeks for 4 months, followed by 480mg every 4 weeks for 8 months).1