First-line treatment with immunotherapy in metastatic squamous NSCLC
Immunotherapy has dramatically changed the therapeutic scenario in the treatment-naïve advanced NSCLC. While the single agent pembrolizumab has become the standard first-line therapy in patients with ≥50% PD-L1 expression on tumor cells, the combination of pembrolizumab and chemotherapy has emerged as an effective first-line treatment regardless of PD-L1 expression in squamous NSCLC.1,2 Furthermore, the combination of pembrolizumab and chemotherapy has shown comparable survival benefit in the Chinese population.3 In a recent symposium, Professor Luis Paz-Ares, Head of Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain discussed first-line immunotherapy treatment in NSCLC and management of lung cancer patients in the era of COVID-19 pandemic.
Single agent immunotherapy with pembrolizumab improved survival benefit in NSCLC patients
Pembrolizumab, a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, is approved as a single agent for the first-line treatment of metastatic NSCLC with PD-L1 TPS ≥1%, and in combination with chemotherapy for metastatic squamous and non-squamous NSCLC irrespective of PD-L1 expression.4 Previously in the non-randomized phase I KETNOTE-001 trial, patients receiving single-agent pembrolizumab had a median OS of 12.0 months.5 In treatment-naïve NSCLC patients, a 5 year OS of 23.2% was observed.6 Subsequent confirmatory open-label phase 3 KEYNOTE-024 trial, pembrolizumab monotherapy was compared to platinum-based chemotherapy in treatment-naïve patients with advanced NSCLC whose tumors express a PD-L1 TPS ≥50%.7 Pembrolizumab was associated with significantly longer progression free survival (PFS) and overall survival (OS) with fewer adverse events than platinum-based chemotherapy.7 A similar OS benefit was also observed between non-squamous and squamous NSCLC patients.7 Prof. Paz-Ares stated, “Due to these data, pembrolizumab monotherapy is considered as standard of care in first-line treatment for metastatic NSCLC with high PD-L1 expression (TPS ≥50%).”
KEYNOTE-407: Combination of pembrolizumab and chemotherapy is effective regardless of PD-L1 expression
The double-blind, placebo-controlled, phase 3 KEYNOTE-407 trial randomized patients with stage IV untreated squamous NSCLC to receive either carboplatin plus paclitaxel or nab-paclitaxel plus pembrolizumab, or placebo.8 The primary endpoints were PFS and OS, and the patients were stratified according to PD-L1 expression (TPS <1% or ≥1%) and the choice of taxane (paclitaxel vs. nab-paclitaxel).8 After a median follow-up of 7.8 months, adding pembrolizumab to standard chemotherapy significantly improved OS over chemotherapy alone: median OS was 15.9 vs. 11.3 months (Hazard ratio (HR) for death=0.64, 95% CI: 0.49-0.85) despite a cross over rate of 31.7%.8 This survival benefit was evident in all the subgroups regardless of PD-L1 expression levels.8 PFS was also improved with pembrolizumab over chemotherapy alone with a median PFS of 6.4 versus 4.8 months (HR for disease progression or death=0.56, 95% CI: 0.45-0.70) with the objective response rate (ORR) almost doubled (58% vs. 38%).8 Pembrolizumab plus chemotherapy showed a safety profile where the frequency and severity of toxicities were similar to chemotherapy alone, with grade 3–5 adverse events occurred in 69.8% of patients in the combination arm vs. 68.2% in the chemotherapy alone arm.8
In addition to OS and PFS, an exploratory primary endpoint PFS-2 explored the time from randomization to progression on next-line treatment/death, whichever occurred first.9 At a median follow-up of 14.3 months in the protocol-specified final analysis, pembrolizumab plus chemotherapy continued to demonstrate a clinically meaningful improvement over placebo plus chemotherapy in OS at 17.1 vs. 11.6 months (HR=0.71; 95% CI: 0.58‒0.88) (Figure 1).9 PFS-2 was longer for patients randomized to first-line pembrolizumab plus chemotherapy than placebo at 13.8 vs. 9.1 months (HR=0.59; 95% CI: 0.49-0.72).9 These results supported pembrolizumab plus chemotherapy as a standard first-line treatment in patients with metastatic squamous NSCLC.9
Most importantly, the addition of pembrolizumab to chemotherapy maintained or improved health related quality of life (HRQoL) measurements relative to baseline and versus chemotherapy alone at weeks 9 and 18.10 In light of these findings, Prof. Paz-Ares emphasized, “These results support the use of pembrolizumab plus chemotherapy as first-line therapy for metastatic squamous NSCLC regardless of PD-L1 expression levels”.
KEYNOTE-407 China extension study shows consistent outcomes with global study
The China extension study was designed similar to the global study.3 Total 125 patients were enrolled. After a median follow-up of 10.4 months, the results showed that the pembrolizumab group had a longer median OS at 17.3 months versus 12.6 months in the control group, indicating that pembrolizumab combined with carboplatin plus paclitaxel reduced mortality by 56% (HR=0.44; 95% CI: 0.24‒0.81) (Figure 2). Median PFS were 8.3 months in the combination arm and 4.2 months in the control arm, indicating that pembrolizumab combined with carboplatin plus paclitaxel reduced the risk of progression or mortality by 68% (HR=0.32; 95% CI: 0.21‒0.49) when compared to control.3
Moreover, pembrolizumab combined with carboplatin plus paclitaxel improved ORR by 36.8% (78.5% vs. 41.7%). Duration of response (DOR) has also improved with the combination of pembrolizumab by 5.4 months.3 The rates of grade 3-5 AEs were similar between the two groups at 89% and 87% in the pembrolizumab plus chemotherapy and placebo plus chemotherapy arms, respectively.3 “The results of the KEYNOTE-407 China extension study are consistent with those of the global KEYNOTE-407 study,” remarked Prof. Paz-Ares.
Understanding lung cancer patients infected by SARS-CoV-2
At the latter part of the symposium, Prof. Paz Ares shared the effects of COVID-19 pandemic on the lung cancer patients by highlighting that “presence of lung cancer or lung metastasis has been shown to correlate with the mortality among cancer patients with COVID-19.” In a cohort study that recruited COVID-19 patients with active or prior hematologic or invasive solid malignancies, all-cause 30-day mortality was found to be significantly associated with the general factors of increasing age, male sex, former smoking, number of comorbidities, and receipt of azithromycin plus hydroxychloroquine; cancer-specific factors of moderate or poor Eastern Cooperative Oncology Group performance status and active (measurable) cancer were also found to be associated with all-cause 30-day mortality. However, as cancer type and treatment were not independently associated with increased 30-day mortality, it is crucial to understand the impact of COVID-19 on patients with lung cancer to ensure optimal care.11
The TERAVOLT is the first global registry aimed at understanding the effect of SARS-CoV-2 infection on patients with thoracic malignancies.12 Among the 428 patients studied in TERAVOLT, the median age was 67.0, 70.0 and 66.5 years in the recovered (n=169), died (n=141), and ongoing hospitalization group (n=118), respectively. A majority of patients were male and were current or former smokers. Notably, the most common histology was NSCLC followed by small-cell lung cancer with most patients having stage IV disease.12 Many patients were being treated with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) and have received 1 line of cancer therapy in the last 3 months with the most common comorbidities being hypertension and COPD.12
The most common presenting symptoms were fever, dyspnea, and cough. Out of the 428 patients studied, 59%, 71% and 33% had developed pneumonia or pneumonitis in the recovered, died, and ongoing hospitalization group, respectively. Notably, patients that have died have a much higher proportion of developing acute respiratory distress syndrome at 49.6% vs. the recovered and ongoing hospitalization group at 4.1% and 11.9%, respectively.12 Interestingly, among the 400 patients that were under ongoing hospitalization or had previous hospital admissions from the recovered or died group, only 8.3% were admitted to the intensive care unit and only 5.0% were mechanically ventilated.12 A total of 141 (35.5%) patients have died, with 112 (79.4%) patients died due to COVID-19 only, 15 (10.6%) patients died due to cancer only, 12 (8.5%) patients died due to cancer and COVID-19 together.12
Multivariate analysis revealed that age older than 65 years and having an Eastern Cooperative Oncology Group (ECOG) Performance Status score =1 was associated with an increased risk of death at a hazard ratio of 1.70 and 2.14, respectively. Most importantly, patients with prior administration of chemotherapy were associated with an increased risk of death when compared to no treatment and immunotherapy or targeted therapy at a hazard ratio of 1.71 and 1.64, respectively.12 This result indicated that immunotherapy or targeted therapy were not associated with an increased risk of death in cancer patients with COVID-19.12
In summary, older age, being a current or former smoker, receiving treatment with chemotherapy alone, and the presence of any comorbidities were associated with an increased risk of death in patients with thoracic malignancies under the COVID-19 pandemic.
Pembrolizumab monotherapy has become the standard first-line therapy for metastatic NSCLC patients with ≥50% PD-L1 expression on tumor (TPS ≥50%) without EGFR or ALK aberrations. Additionally, pembrolizumab combined with chemotherapy significantly improved the OS, PFS, ORR for patients with squamous metastatic NSCLC. This regimen is well tolerated by these patients. Therefore, combination therapy of pembrolizumab and chemotherapy is preferred over chemotherapy alone regardless of PD-L1 expression. For the Chinese population, first-line treatment with pembrolizumab combined with chemotherapy also significantly improved the survival benefits. Pembrolizumab has broadly revolutionized the first-line treatment of advanced NSCLC patients with no oncogenic drivers.
Safeguard children’s health from Omicron-associated complications with BNT162b2
The fifth wave of Coronavirus disease 2019 (COVID-19) has caused more than a million people being infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Omicron BA.2, predominant) and over 9,000 COVID-19-associated deaths in Hong Kong.1 Children, a subgroup of the population who had experienced more favorable outcomes vs. the older adults during the first 4 waves of the pandemic, were reported to have disproportionately higher hospitalization rates under the Omicron era.2 Some studies revealed that seizure and laryngotracheobronchitis, or croup, were common severe complications which led to pediatric hospitalization.2 The findings highlighted the importance of COVID-19 vaccination among children, but those aged <5 years were still not eligible for this mitigation measure. In an interview with Omnihealth Practice, Dr. Leung, Sze-Yin Agnes presented the latest safety and efficacy data of BNT162b2 among children aged ≥6 months and encouraged parents to arrange COVID-19 vaccination for their children to reduce the negative impact of this pandemic in young children.
Addition of molnupiravir in the evolving SARS-CoV-2 treatment landscape
At a symposium organized by the Hong Kong Society for Infectious Diseases, Dr. Marissa Grifasi Williams kicked off the symposium by sharing how the evolution of virus has changed the management of SARS-CoV-2, highlighting the current guidelines to recommend molnupiravir as an oral therapy for the coronavirus disease 2019 (COVID-19). She further discussed the MOVe-OUT trial, which demonstrated that molnupiravir reduced the risk of hospitalization or death in at-risk and unvaccinated COVID-19 adults. Concluding her presentation, Dr. Williams featured the additional data of molnupiravir from the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 2022, validating that molnupiravir was effective in clearing the virus as early as 3 days, as well as improving symptoms. Then, Dr. Yap, Yat-Hin Desmond shared his experience in managing COVID-19 patients with renal failure in Hong Kong.
Multi-peptide CoVac-1 vaccine induces T-cell immunity in immunoglobulin-deficient cancer patients
In the American Association for Cancer Research (AACR) annual meeting 2022, Dr. Claudia Tandler from the University of Tübingen, Germany, discussed the safety and immunogenicity of a novel multi-peptide vaccine, CoVac-1, for the induction of a (SARS-CoV-2) T-cell immunity in cancer patients with dis
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
BNT162b2 boosters and beyond: Strategies to overcome waning immune responses against omicron variant
During the fifth wave of Coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [B.1.1.529 (Omicron), predominant] infected over a million people and claimed more than 9,000 lives in Hong Kong.1 Elderly people aged ≥60 years were the most vulnerable population and accounted for ≥95% of the total death cases.1 Among the deceased, most were unvaccinated (>70%), or had received only 1 dose of COVID-19 vaccine, and/or were with known chronic diseases.1 Even for people who have received 2 doses of vaccines, increasing evidence showed that protection against severe COVID-19 would be reduced due to the waning immune responses against the Omicron variant.2 As such, in an interview with Omnihealth Practice, Professor HUNG, Fan-Ngai Ivan, addressed the rising concern about Omicron and presented the latest data showing that BNT162b2 boosters are still highly effective against the new threat. He also provided some updates on the development of new Omicron-adapted vaccines for conferring better protection to people.
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.
Emerging from covid-19 predicament: An update on its management and vaccination
The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has afflicted more than 200 million people, with a death toll of more than 4 million people worldwide.1 As of September 29, 2021, Hong Kong has recorded 12,210 COVID-19 cases with 213 deaths.2 Although the situation in Hong Kong has been stabilized since the end of the fourth wave of epidemic in May 2021, the emergence of variants, especially the Delta variants, could be another threat to our society.3,4 In a lecture held by the Macau Association of Health Service Executives (MAHSE), Professor Hung, Fan-Ngai Ivan addressed the concerns over the emergence of the Delta variant and provided an update on the COVID-19 management and vaccination.