CONFERENCE UPDATE: WCLC 2020
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 identify potential well-responders.1 Response assessment by conventional imaging is frequently unable to identify patients who will achieve durable clinical benefit (DCB), and the radiologic assessment of ICI response is neither accurate nor prompt.2,3 Dr. Qing Zhou, Guangdong Lung Cancer Institute, China, explained that tissue biomarkers are traditionally obtained from tissue biopsies which require invasive, risky and costly surgical interventions.2 Also, sufficient tumor tissue molecular analysis may not be obtainable in a substantial number of patients.2 As a result, it may be more difficult to find monitoring biomarkers to predict drug response, resistance and disease relapse for immunotherapy than for genomic or proteomic therapy.
To address the unmet needs from tissue biomarkers, circulating tumor DNA (ctDNA) is a promising biomarker that is expected to have greater specificity than most serum protein markers as it is a byproduct of dying cancer cells - its level provides a real-time snapshot of active tumor cell death.1 In a study that evaluated the longitudinal changes in ctDNA levels among NSCLC patients receiving ICIs, ctDNA response was found to precede and correlate with radiographic response of tumors.1 In addition, a reduction in ctDNA level to half its pre-treatment value was associated with improved patient survival, indicating that ctDNA monitoring could provide an early measure of therapeutic efficacy.1 Peripheral CD8 T-cell levels were also found to be independently associated with DCB in stage IV NSCLC patients receiving programmed death ligand-1 (PD-L1) blockade-based ICIs.2 As such, the benefit of ICIs can be better predicted by integrating pre-treatment ctDNA, pretreatment circulating immune cell profiling and early on-treatment ctDNA dynamics in a Bayesian model than assessing the individual parameters.2 Using this model, subsequent treatment strategies following PD-L1 or other ICIs can be better personalized.2
Apart from predicting the drug response, ctDNA can also be used to identify patients at high risk of disease recurrence by monitoring the post-surgical minimal residual disease (MRD).6 As MRD is defined as cancer that persists after treatment, ctDNA can be used to monitor this occult stage of cancer progression.4 In addition, circulating tumor cells (CTCs) can enable subsequent analyses at the DNA, RNA and protein levels to compliment ctDNA analyses that identify genetic and epigenetic changes in the DNA.4 The use of CTCs and ctDNA for detecting micro-metastasis would also enable the testing of new adjuvant or post-adjuvant treatment strategies to delay or prevent disease progression, and Dr. Zhou shared that there are several ongoing clinical trials that investigate MRD monitoring after adjuvant ICI treatment.4
However, Dr. Zhou also pointed out that ctDNA monitoring remains a clinical challenge in practice. As only a small amount of ctDNA is shed by tumors during the early cancer stage, the most sensitive NGS-based method to detect ctDNA, i.e.,CAPP-seq method, can only detect 50% of stage I cancer. ctDNA levels need to be quantified using maximum or mean variant allele frequencies or ctDNA concentration and do not have a consistent definition. Additionally, a positive ctDNA response is variably defined as any decrease from baseline to up to 90% decrease from baseline. Similarly, the challenges of monitoring MRD also include determining the detection threshold, as well as optimal detection time and follow-up intervals. “In the future, we need to do the clinical decision-making model based on big data and artificial intelligence mechanistic learning. We can combine the baseline data, dynamic biomarker data and long-term survival data in one model, so that we can make the best clinical decision for a specific patient,” concluded Dr. Zhou.
NIVO + chemo improves EFS in patients with resectable IB-IIIA NSCLC: the phase 3 CheckMate 816 trial
Improving long-term survival in patients with resectable non-small cell lung cancer (NSCLC) is still essential, despite advancements in the adjuvant therapies.1 The CheckMate 816 trial previously demonstrated a significant improvement in the pathologic complete response (pCR) with neoadjuvant nivolumab (NIVO) + chemotherapy (chemo) compared with chemo alone in patients with resectable NSCLC, and maintained a good tolerability profile.1 As a result, this regimen has currently gained approval from the United States for the treatment of adult patients with resectable NSCLC.1
The potential new first-line mNSCLC treatment regardless of PD-L1: Durvalumab + tremelimumab + chemotherapy improved survival
Over the past decades, treatment options in advanced non-small cell lung cancer (NSCLC) patients without oncogenic drivers have been limited to cytotoxic chemotherapies with poor survival outcomes.1 Although patients’ overall survival (OS) has been prolonged with the current standard of care (SoC) (i.e. pembrolizumab with or without chemotherapy) in recent years, the clinical outcomes are still suboptimal.2,3 Dual immunotherapy, which brought substantial survival improvements across multiple malignancies such as advanced melanoma, sheds light on the further advance of metastatic NSCLC (without driver mutations) management.4 The combination of nivolumab (NIVO) and ipilimumab (IPI) with or without chemotherapy has demonstrated superior survival benefits in these patients, leading to the regulatory approval from the United States (US) Food and Drug Administration (FDA).5,6 More recently, the efficacy of durvalumab and tremelimumab plus chemotherapy (D + T + CT) in treatment-naïve metastatic NSCLC patients has also been evaluated in the POSEIDON trial.7 In a webinar organized by the Hong Kong Precision Oncology Society, Dr. Melissa L. Johnson presented the encouraging data from POSEIDON and discussed the latest advances of immunotherapy in metastatic NSCLC. Dr. Au, Siu-Kie Joseph also shared his expert insights on the new POSEIDON data and discussed their impacts on the local clinical practice in an interview with Omnihealth Practice.
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.
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
DFS improvement with atezolizumab versus BSC after adjuvant chemotherapy: Phase 3 IMpower010 trial
Adjuvant chemotherapy is a standard of care after complete surgical resection in patients with early-stage non-small-cell lung cancer (NSCLC).1 The phase 3 IMpower010 trial aimed to evaluate adjuvant atezolizumab (anti-programmed death-ligand 1 (PD-L1)] versus best supportive care (BSC) after adjuvant platinum-based chemotherapy in patients with completely resected NSCLC, at the disease-free survival (DFS) interim analysis.2 The study randomized 1,005 people with a ratio of 1:1 to receive adjuvant atezolizumab (1,200mg every 21 days; for 16 cycles or 1 year) or BSC following surgical resection (4-12 weeks prior) and up to 4 cycles of adjuvant cisplatin-based chemotherapy.2 The possible impact on DFS and types of surgery therapies prior to adjuvant atezolizumab were also examined. DFS was presented by disease stage and nodal status (NO vs. N1 vs. N2).3
Lung cancer in the evolving field of precision medicine
According to Dr. David Gandara, University of California Davis, Comprehensive Cancer Center, United States, the requisites for implementing precision medicine are: i) the ability to profile tumors for biomarkers, ii) having drugs against these biomarker targets, and iii) having clinical trial design
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
Applying low-dose computerized tomography for lung cancer screening in Taiwan
Lung cancer is the leading cause of cancer death worldwide, accounting for nearly 20% of all cancer deaths.1 Previously, low-dose computerized tomography (LDCT) was shown to detect asymptomatic lung cancer cases better than chest radiography, and many countries in the West have initiated small rando