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.
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 breakthough 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.
Combination of durvalumab, tremelimumab and chemotherapy as a potential new first-line mNSCLC treatment option
Immunotherapies targeting the programmed death protein 1 (PD-1)/programmed death-ligand1 (PD-L1) pathway, either administered as a monotherapy or in combination with chemotherapy, have transformed the lung cancer treatment.' While the inclusion of chemotherapy to anti-PD-L1 may provide early disease control, adding anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) to anti- PD-L1 with or without chemotherapy may confer long-term survival benefits for some patients. 1
POSEIDON is a randomized, open label, multicenter phase 3 study evaluating durvalumab with and without tremelimumab in combination with chemotherapy regimens as first-line treatment for squamous or non-squamous metastatic non-small cell lung cancer (mNSCLC).' The eligible patients with metastatic non-small cell lung cancer (mNSCLC) received a combined regimen of durvalumab, tremelimumab, and chemotherapy. Progression-free survival significantly improved for patients receiving durvalumab plus chemotherapy compared with chemotherapy alone, with a positive trend for overall survival that did not reach statistical significance.'
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
Monitoring biomarkers in non-small cell lung cancer patients treated with immune checkpoint inhibitors
The introduction of immune checkpoint inhibitors (ICIs) has revolutionized the approach to advanced non-small cell lung cancer (NSCLC) by offering durable disease control with less side effects than traditional chemotherapy.1 However, as most patients do not benefit from ICIs, it is important to ide
Artificial intelligence platforms enable population-wide lung cancer screening programs
Lung cancer is the leading cause of cancer death worldwide that accounted for 18.4% of all cancer deaths.1 In Hong Kong, lung cancer was associated with a crude mortality rate of 51.7% in 2018 and is considered the most common cause of cancer death.2 Previously, population screening with low-dose co
Neoadjuvant singular immunotherapy versus perioperative chemoimmunotherapy for early-stage lung cancer
Dr. Mariano Provencio, Hospital Universitario Puerta de Hierro, Spain, explained that options to improve poor lung cancer survival include adjuvant treatment for stage I and II and neoadjuvant treatment for stage III disease. Where both neoadjuvant and adjuvant treatments provide a clinically signif