With the World Conference on Lung Cancer (WCLC) 2020 completed last January, several new and clinical relevant phase 2 and phase 3 studies on Lung Cancer have been published. We summarised some key data for you.
Women account for a disproportionate percentage of new human immunodeficiency virus (HIV) infections in sub-Saharan Africa, comprising 59% of 18 million new adult HIV infections in 2017.
Kidney transplants are the best treatment for end-stage renal disease (ESRD), with better survival outcomes than haemodialysis or peritoneal dialysis. However, in Hong Kong as well as much of the rest of the world, there is an increasing gap between the number of patients requiring a transplant and the number of organs available.
Seasonal influenza is common between January to March, and July to August in Hong Kong. Baloxavir marboxil is the first influenza antiviral with a novel mechanism of action to be approved in almost two decades, and was registered for use in Hong Kong in February 2019.
Know all the United States Food and Drug Administration (U.S. FDA) approved immune-checkpoint inhibitors. Members of MediPaper can download the free PPT slides summarising the U.S. FDA approved immune-checkpoint inhibitors and other U.S. FDA approved immunotherapies.
RAS is the most frequently mutated gene family in cancers, with KRAS mutations being involved as a driver in three of the most lethal cancers – lung cancer, colorectal cancer, and pancreatic cancer. Incidence of KRAS mutations vary between ethnicity with Caucasians having a higher incidence than African-Americans or Asians. In non-small lung cancer (NSCLC), the most common KRAS mutation is G12C. In Asia, G12C mutations in particular account for 14.5% of KRAS mutations in the Chinese population. KRAS G12C was identified in 4.3% of lung cancer samples and 2.5% of colorectal cancer samples.
A number of tyrosine kinase inhibitors (TKIs) are now available for the treatment of various types of non-small cell lung cancers (NSCLC), including epidermal growth factor receptor (EGFR)-mutated and anaplastic lymphoma kinase (ALK)-rearranged NSCLC. However, amplification of the MET gene, which codes for the hepatocyte growth factor receptor (HGFR), has been found to be one of the most prominent mechanisms of secondary resistance to EGFR TKIs. Similarly, the MET exon 14 (METex14) mutation has also emerged as a potential tumour driver due to its role in cancer proliferation, and thus also a promising target for NSCLC.
Aberrant RET activation has shown to be a clinical driver of tumour growth and proliferation. It is reported that 1-2% of non-small cell lung cancer patients have activating RET fusions. Clinical characteristics of these patients are generally younger (<60 years) with minimal or no smoking history, and frequent presentation with brain metastases at diagnosis of advanced disease. RET mutations are mutually exclusive with other common lung cancer genetic abberations, such as reported for KRAS, EGFR, and ALK.
This year, ASCO 2020 was held as a virtual conference due to the COVID-19 pandemic. This is a summary of key trials presented at ASCO, focusing primarily on breast cancer, liver cancer, and lung cancer.
Non-small cell lung cancer (NSCLC) was a key feature of the American Society of Clinical Oncology (ASCO) 2019 annual meeting. This year, exciting results with neoadjuvant immunotherapy (I-O) from the LCMC3, NEOSTAR, and GECP16/03_NADIM studies as well as combinations of I-O and PARP-inhibitors with chemoradiation therapy, and more. A summary of 36 oral presentations on NSCLC, SCLC, and Mesothelioma.
On 11 April 2019, the FDA approved single-agent pembrolizumab (Keytruda®, Merck) for the first-line treatment of stage III/IV non-small cell lung cancer (NSCLC) patients with a PD-L1 Tumor Proportion Score (TPS) ≥1% who are not amenable to surgical resection or definitive chemoradiation and who have no known EGFR or ALK genomic aberrations.
On 18 March 2019, the FDA approved atezolizumab (Tecentriq®, Genentech) plus carboplatin and etoposide as front-line treatment of adult extensive-stage small cell lung cancer (ES-SCLC) patients.
On 6 December 2018, the FDA approved atezolizumab (Tecentriq®, Roche/Genentech) plus bevacizumab and chemotherapy with paclitaxel and carboplatin for the frontline treatment of metastatic non-squamous non-small cell lung cancer (NSq NSCLC) patients not harbouring any EGFR or ALK genomic tumour aberrations.
On November 2nd 2018, lorlatinib (LORBRENA®, Pfizer) received accelerated approval by the FDA for the second- and third-line treatment of patients with metastatic, anaplastic lymphoma kinase (ALK)-positive, non-small cell lung cancer (NSCLC). Third-line patients should have had progression on crizotinib and another ALK-inhibitor for metastatic disease, and second-line patients should have had progression on either alectinib or ceritinib in the first-line for metastatic disease.
On October 30th 2018, the FDA approved the use of programmed death 1 (PD-1) inhibitor pembrolizumab (Keytruda®, Merck) in combination with carboplatin plus paclitaxel or nab-paclitaxel for the first-line treatment of patients with metastatic squamous non-small cell lung cancer (NSCLC).
Pembrolizumab (Keytruda®, Merck) in combination with chemotherapy was associated with longer overall survival (OS) and progression-free survival (PFS) when compared to placebo plus chemotherapy in patients with untreated metastatic squamous cell non-small cell lung cancer (NSCLC).
Brigatinib (Alunbrig®, Ariad) significantly prolongs the progression-free survival (PFS) in anaplastic lymphoma kinase (ALK) inhibitor-naïve patients with ALK-rearranged non-small cell lung cancer (NSCLC) when compared to crizotinib, as resulted from the ALTA-1L study.
Avelumab (Bavencio®, Merck KGaA) does not improve the overall survival (OS) in non-small cell lung cancer (NSCLC) patients previously treated with platinum-doublet chemotherapy, as resulted from the JAVELIN Lung 200 study (NCT02395172). The safety profile favoured avelumab over docetaxel.
On September 27, 2018, the FDA approved dacomitinib (Vizimpro®, Pfizer) as first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or exon 21 L858R mutations as confirmed by an FDA-approved test.
An interim analysis of the Phase III IMpower132 study showed that atezolizumab (Tecentriq®, Roche/Genentech) plus platinum-based chemotherapy (cisplatin or carboplatin) with pemetrexed improves the median progression-free survival (PFS) in treatment-naïve patients with non-squamous non-small cell lung cancer (NSCLC). The median PFS for atezolizumab plus pemetrexed and a platinum salt was 7.6 months vs 5.2 months with chemotherapy alone (HR=0.60, 95% CI: 0.49-0.72; p<0.0001).
First-line osimertinib was associated with a clinically meaningful progression-free survival (PFS) improvement when compared to a standard-of-care (SOC) epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) in a sub-analysis of Asian patients who participated in the FLAURA trial (NCT02296125).
The combination capmatinib (INC280, Novartis) plus gefitinib (Iressa®, AstraZeneca) showed promising, early phase efficacy in patients with mesenchymal-epithelial transition factor (MET)-dysregulated and epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC).
A high tumour mutational burden in the plasma (bTMB) is a clinically actionable biomarker for atezolizumab (Tencentriq®, Roche) treatment in patients who failed 1st-line platinum-based therapy for advanced non-small cell lung cancer (NSCLC).
Biosceptre has announced the initiation of its Phase 1 clinical study with the peptide vaccine BIL06v. BIL06v is a peptide-protein conjugate that recruits the patient’s immune system to make antibodies specifically targeted at nfP2X7-expressing cancer cells resulting in tumour cell death.
On 20th of August 2018, the FDA granted regular approval for pembrolizumab (Keytruda®, Merck) plus pemetrexed and a platinum salt in the first-line treatment of patients with metastatic, non-squamous non-small cell lung cancer (NSCLC), not harbouring any EGFR or ALK genomic tumour aberrations.
HONG KONG, CHINA – 13 August 2018 – Sihuan Pharmaceutical Holdings Group Ltd. (HKEx: 0460), announced that its innovative in-house developed oncology drug pirotinib has commenced into Phase II Clinical testing in China following the completion of a Phase I clinical trial in three renowned cancer research centres in the United States.
Osimertinib is active in the second-line treatment of patients with T790M-positive advanced non-small cell lung cancer (NSCLC) and central nervous system (CNS) metastases, as reported by the investigators of the Phase III AURA3 study.
First-line atezolizumab plus bevacizumab, carboplatin and paclitaxel improves PFS in patients with non-squamous NSCLC. Two presentations on the IMPower150 study by Martin Reck (ELCC 2018) and Mark Socinski (AACR 2018) discussed the frontline addition of atezolizumab to bevacizumab and chemotherapy in different lung cancer subgroups (NCT02366143).
AACR 2018: First-line nivolumab-ipilimumab in TMB-high NSCLC with was associated with a more than tripled 1-year progression-free survival (PFS) rate compared to platinum-based chemotherapy in the Phase III CheckMate 227 trial (NCT02477826).
FDA approved osimertinib (Tagrisso, AstraZeneca Pharmaceuticals LP) for the 1st-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.
AACR 2018: Frontline pembrolizumab plus chemotherapy in NSCLC reduces the risk of death by more than 50%. The Phase III KEYNOTE-189 trial combined pembrolizumab (Keytruda®) plus standard of care platinum-based chemotherapy in non-squamous non–small cell lung cancer (NSCLC) without EGFR or ALK genetic aberrations (NCT0278680)
Pembrolizumab (Keytruda®) as single-agent immunotherapy in the frontline setting of any histology NSCLC with a PD-L1 expression ≥1% was associated with improved overall survival (OS) when compared to platinum-doublet chemotherapy in the KEYNOTE-042.
Crizotinib in Asian NSCLC patients with ROS1 alterations was associated with a 71.7% objective response rate (ORR) with a median duration of response (DOR) of 19.7 months (95% CI, 14.1 months – not reached). Learn more about the results with crizotinib in East-Asian non-small cell lung cancer (NSCLC) patients harbouring c-ros oncogene 1 (ROS1) rearrangements.
- FDA approved durvalumab (Imfinzi, AstraZeneca Inc.) for patients with unresectable stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy. More Information.
- FDA granted approval to afatinib (Gilotrif, Boehringer Ingelheim Pharmaceutical, Inc.) for a broadened indication in 1st-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumours have non-resistant epidermal growth factor receptor (EGFR) mutations as detected by an FDA-approved test. More Information.