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.
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
Confirmed OS benefits of adjuvant osimertinib in resected EGFR-mutated stage IB-IIIA NSCLC patients: The ADAURA trial
The ADAURA trial was a randomized, double-blind, placebo-controlled, phase 3 study that evaluated the survival benefits of adjuvant osimertinib, an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), in the treatment of patients with completely resected EGFR-mutated stage IB-IIIA non-small cell lung cancer (NSCLC).1 A total of 682 adult patients with completely resected stage IB, II, IIIA NSCLC were recruited and randomized 1:1 to receive either osimertinib 80mg daily or placebo for 3 years until disease recurrence or treatment completion.1 The primary endpoint of the ADAURA trial was disease-free survival (DFS) in stage II-IIIA patients.1 Overall survival (OS) is one of the key secondary endpoints of the ADAURA trial.1
Sotorasib demonstrates consistent clinical benefits in KRAS G12C-mutation advanced NSCLC regardless of genomic co-alterations: Subgroup analysis of CodeBreaK 200
The CodeBreaK 200 trial was the first randomized, phase 3 trial that compared the efficacy between sotorasib and docetaxel in patients with Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C-mutated advanced non-small cell lung cancer (NSCLC).1 A cohort of 345 adults with locally a
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
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.