NEWS & PERSPECTIVE
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
The current standard treatment for stage IB-IIIA NSCLC is surgery, followed by adjuvant chemotherapy.2 Yet, emerging studies have highlighted the role of other adjuvant therapies such as immunotherapies in improving DFS in these patients.3,4 Pembrolizumab, a programmed death-1 receptor blocker (anti-PD-1), has previously been shown to be effective in improving survival and clinical outcomes as a first-line treatment for NSCLC with a significant programmed death-ligand 1 (PD-L1) expression.5 The PEARLS/KEYNOTE-091 trial further investigated the role of pembrolizumab in the adjuvant setting of stage IB-IIIA NSCLC with any PD-L1 expression levels.1
The trial recruited 1,177 patients aged ≥18 years from 196 medical centers across 29 countries, with any pathologically confirmed NSCLC of stage IB-IIIA as per the American Joint Committee on Cancer (AJCC) staging system that has been completely surgically resected and has a known PD-L1 expression status.1 Adjuvant chemotherapy was to be considered for stage IB disease and was strongly recommended for stage II and IIIA disease as per the local guidelines.2 Participants were randomized into the pembrolizumab group or the saline placebo group, given intravenously every 3 weeks until recurrence, having other clinically adverse events (AEs), or completion of 18 administrations.1 The primary endpoints included DFS in the overall population and the subpopulation with a PD-L1 tumor proportion score (TPS) of ≥50%.1 In both populations, the median ages were 65 years, with most patients having previously received 3 or 4 cycles of adjuvant chemotherapy with a cisplatin and/or carboplatin-based regimen.1 The median follow-up was 35.6 months.1
In the overall population, 212 of 590 patients (36%) and 260 of 587 patients (44%) in the pembrolizumab and placebo groups, respectively, had a DFS event, with the median DFS being 53.6 months in the pembrolizumab group and 42.0 months in the placebo group (HR=0.76; 95% CI=0.63-0.91; p=0.0014).1 Within the population of PD-L1 TPS ≥50%, 54 of 168 patients (32%) and 63 of 165 patients (38%) in the pembrolizumab and placebo groups, respectively, had a DFS event (HR=0.82; 95% CI: 0.57-1.18).1 In both populations, the most common DFS event was recurrence.1
The rates of treatment-related serious adverse events (TEAEs) in the pembrolizumab and placebo groups were 12% (n=68) and 2% (n=13), respectively, with pneumonitis (2%; n=12) and diarrhea (1%; n=6) being the most common among patients treated with pembrolizumab, and pneumonitis (1%; n=3), and colitis (<1%; n=2) in the placebo arm.1
To conclude, adjuvant pembrolizumab monotherapy showed significant and clinically meaningful improvement in DFS vs. placebo in stage IB-IIIA NSCLC after complete resection and, when recommended, adjuvant chemotherapy, regardless of PD-L1 expression.1 Yet, a longer follow-up is warranted to determine whether the DFS benefit with pembrolizumab will translate into an overall survival (OS) benefit.1
- O’Brien M, et al. Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB–IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. Lancet Oncol. 2022;23(10):1274-1286.
- Postmus PE, et al. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(Suppl 4):iv1-21.
- Wu YL, et al. Osimertinib in resected EGFR-mutated non–small-cell lung cancer. N Engl J Med. 2020;383(18):1711-1723.
- Felip E, et al. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB–IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021;398(10308):1344-1357.
- Aguilar EJ, et al. Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression. Ann Oncol. 2019;30(10):1653-1659.
Novel immunotherapeutic target for HCC: The role of Δ42PD-1
The study conducted by a group of researchers from the University of Hong Kong (HKU) has provided insight into the mechanism behind hepatocellular carcinoma (HCC) patient’s resistance to the programmed death 1 (PD-1) immune checkpoint blockade (ICB), contributing to the understanding of HCC therapy
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.
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.
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
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
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
Immunotherapy eliminates tumor cells in early-stage triple-negative breast cancer (KEYNOTE-522 study)
Triple-negative breast cancer (TNBC) is an aggressive form of the disease accounting for 10-20% of all breast carcinomas and characterized by the low expression of progesterone receptor, estrogen receptor, and human epidermal growth factor receptor 2.1