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.
What is new in oncology targeted therapies? Read our oncology targeted therapies blog and learn more about the advancements in oncology targeted therapies.
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With the San Antonio Breast Cancer Conference (SABCS) 2020 by AACR just completed, several new and clinical relevant phase 2 and phase 3 have been published in the Journal of the American Medical Association, Clinical Cancer Research, New England Journal of Medicine, Journal of Clinical Oncology, and Lancet Oncology. [‘mediPr] provides you with an overview.
Lung cancer is a leading cause of cancer-related death. In East Asian non-small cell lung cancer (NSCLC) patients, epidermal growth factor receptor (EGFR) mutations occur in 40-55% of lung adenocarcinomas.
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.
Conventional imaging with computed tomography (CT), magnetic resonance imaging (MRI) and bone scans, are the current standard of care for imaging prostate cancer. Accurate imaging primarily relies on nodal metastases size for detection.
Hepatocellular carcinoma (HCC) accounts for 80% of all liver cancers, and 55% of all HCC cases worldwide are reported from China. In Hong Kong, liver cancer is the fourth most common cancer and the third most common cause of cancer death.
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.
The development of new targeted therapies for non-small cell lung cancer (NSCLC) in recent years has changed the standard of care for the later stages of NSCLC in specific population groups.
Precision therapies were first approved for cancer in 1998, when trastuzumab was approved for HER2+ breast cancer, opening the door for other targeted therapies such as imatinib for Philadelphia chromosome-positive chronic myelogenous leukaemia.
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.
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Adding capivasertib to fulvestrant improves the progression-free survival (PFS) in postmenopausal women with oestrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, advanced breast cancer resistant to aromatase inhibitors, concluded Jones et al. (2020) in Lancet Oncology.
Adding capivasertib to paclitaxel improved the progression-free survival (PFS) in patients with metastatic triple-negative breast cancer (TNBC) who had not received prior treatment for metastatic disease. Predominantly patients with PIK3CA/AKT1/PTEN-altered tumours had a more pronounced PFS and overall survival (OS) benefit, as reported by Schmid et al. in the Journal of Clinical Oncology
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.
Breast cancer: a front-runner when it comes to the development of novel therapeutic strategies. With the advent of newer targeted- and immunotherapies, oncologists have an increment of options to offer their patients. The American Society of Clinical Oncology’s (ASCO) 2019 Breast Cancer track offered an extensive look at the latest advancements and updates from on-going trials covering the various subtypes of breast cancer.
On 10 May 2019, the FDA approved single agent ramucirumab (Cyramza®, Eli Lilly) for the treatment of hepatocellular carcinoma (HCC) patients previously treated with sorafenib and who have an alpha-fetoproteintein (AFP) of ≥ 400 ng/mL.
On the 3rd of May 2019, the FDA approved ado-trastuzumab emtansine (Kadcyla® [T-DM1], Genentech/Roche) as adjuvant therapy for human epidermal growth factor receptor (HER2)-positive early breast cancer (EBC) patients with residual invasive disease after neoadjuvant treatment with a taxane and trastuzumab.
On the 2nd of May 2 2019, the FDA approved ivosidenib (Tibsovo®, Agios) as treatment for newly-diagnosed acute myeloid leukaemia (AML) patients ≥75 years old and AML patients with comorbidities precluding intensive induction chemotherapy. Patients should harbour a susceptible IDH1 mutation, as per the FDA-approved Abbott RealTime™ IDH1 Assay, to be legible for ivosidenib treatment.
On 19 April 2019, the FDA approved the programmed death 1 (PD-1) inhibitor pembrolizumab (KEYTRUDA®, Merck) plus axitinib – a selective and potent receptor tyrosine kinase inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 – as a first-line treatment for advanced renal cell carcinoma (RCC) patients.
Combining programmed death 1 ligand (PD-L1) inhibitor atezolizumab with MEK-inhibitor cobimetinib in patients with previously treated metastatic colorectal cancer (mCRC) does not improve the overall survival (OS) when compared to regorafenib, as was reported by the investigators of the IMblaze370 (NCT02788279) trial in the Lancet Oncology.
On 4 April 2019, the US FDA approved palbociclib (Ibrance®, Pfizer) plus aromatase inhibitor or fulvestrant for the treatment of male patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer.
On 12 April 2019, the FDA granted accelerated approval to erdafitinib (Balversa®, Janssen) for the treatment of locally advanced or metastatic urothelial cell carcinoma (mUCC) progressed during or following a platinum-containing regimen, including progression within 12 months of (neo)adjuvant platinum-based chemotherapy, and whose tumours harbour susceptible fibroblast growth factor receptor (FGFR) 3 or FGFR2 genetic alterations as determined by the FDA approved companion diagnostic (CDx), the therascreen® FGFR RGQ RT-PCR Kit by Qiagen.
On 18 January 2019, the FDA approved the Herceptin®-biosimilar Ontruzant® (trastuzumab-dttb, Samsung BioEpsis), a HER2/neu receptor antagonist, for patients with HER2-overexpressing (HER2+) breast cancer in the adjuvant and metastatic setting, and in metastatic HER2+ gastric cancer patients. Ontruzant® was approved as biosimilar, not as an interchangeable product.
On 14 January 2019, the FDA approved cabozantinib (Cabometyx®, Exelixis) for hepatocellular carcinoma (HCC) patients previously treated with sorafenib.
On 19 December 2018, the FDA approved olaparib (Lynparza®, AstraZeneca) as a maintenance treatment for adult advanced epithelial ovarian, fallopian tube or primary peritoneal cancer patients who achieving a complete or partial response to first-line platinum-based chemotherapy and who have deleterious germline or somatic BRCA-mutatations (gBRCAm or sBRCAm) by an FDA-aproved test or who are suspected to have deleterious BRCA-mutatations (BRCAm).
On 14 December 2018, the FDA approved the Herceptin®-biosimilar Herzuma® (trastuzumab-pkrb, Celltrion), a HER2/neu receptor antagonist, for patients with HER2-overexpressing (HER2+) breast cancer. Herzuma® was approved as biosimilar, not as an interchangeable product.
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 the first day of the 2018 American Society of Hematology (ASH) Annual Meeting, an additional year of follow-up data from the practice-changing MURANO study were presented to the audience by Professor John F. Seymour. In the trial’s setting of relapsed/refractory (R/R) chronic lymphocytic leukaemia (CLL), the non-chemo-containing regimen venetoclax (Venclexta®, AbbVie/Roche) plus rituximab was associated with maintained superior progression-free survival (PFS) and overall survival (OS) over standard-of-care chemoimmunotherapy with bendamustine plus rituximab. At the same time, a durable post-treatment disease control is also attainable with the fixed-duration chemo-free regimen.
On 28 November 2018, the FDA approved gilteritinib (Xospata® [ASP2215], Astellas) for the treatment of adult patients with relapsed or refractory (R/R) acute myeloid leukaemia (AML) harbouring FLT3 mutations as confirmed by an FDA-approved companion diagnostic test (CDx).
On 26 November 2018, the FDA granted accelerated approval to the first-in-class tropomyosin receptor-kinase (TRK) inhibitor larotrectinib (Vitrakvi®, Loxo Oncology/Bayer) for the treatment of adult and paediatric patients with solid tumours that are metastatic or not amenable to surgery, harbour the neurotrophic receptor tyrosine kinase (NTRK) gene fusion in the absence of known acquired resistance mutations, and whose cancer progressed following treatment or for whom are no satisfactory other treatment options available.
On 21 November 2018, the FDA granted accelerated approval to venetoclax (Venclexta®, AbbVie/Genentech) in combination with either azacitidine, or decitabine, or low-dose cytarabine (LDAC), for the treatment of newly-diagnosed acute myeloid leukaemia (AML) patients ≥75 years old or in patients with comorbidities precluding intensive induction chemotherapy.
On 21 November 2018, the FDA approved glasdegib (Daurismo®, Pfizer) in combination with low-dose cytarabine (LDAC), for the treatment of newly-diagnosed acute myeloid leukaemia (AML) in patients of 75 years or older and in patients with comorbidities contraindicating intensive induction chemotherapy.
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.
Whereas this year’s American Society of Clinical Oncology Annual Meeting (ASCO 2018) boasted two Phase III studies and four Phase II studies with notable results in hepatocellular carcinoma (HCC), the trend did not continue to the European Society for Medical Oncology Conference (ESMO 2018), held in Münich, Germany between October 19-23, 2018. The focus for this years ESMO was mostly on biliary-tract cancers (BTC). Welcome to the hepatobiliary track of ESMO 2018.
On October 16, 2018, the FDA approved PARP-inhibitor talazoparib (Talzenna®, Pfizer) for use in patients with deleterious or suspected deleterious germline BRCA-mutated locally advanced or metastatic human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Patients should be selected for the PARP inhibitor (PARPi)-treatment using an FDA-approved companion diagnostic (CDx) for talazoparib.
SUZHOU, China, Oct. 14, 2018 /PRNewswire/ — The combination therapy of novel programmed death 1 (PD-1) antibody IBI308 (sintilimab, Innovent Biologics) with biosimilar bevacizumab antibody IBI305 (Innovent Biologics) has received the investigational new drug (IND) application for clinical development approval by the National Medical Products Administration (NMPA, formerly known as CFDA) in China.
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.
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.
On September 24, 2018, the US FDA granted regular approval to duvelisib (Copiktra®, Verastem) for the treatment of adult patients with relapsed or refractory (R/R) chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL) after ≥2 prior therapies.
On September 24, 2018, the US FDA granted accelerated approval to duvelisib (Copiktra®, Verastem) for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) after ≥2 prior therapies.
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).
On September 13, 2018, the FDA approved moxetumomab pasudotox-tdfk (Lumoxiti®, AstraZeneca) for adult patients with relapsed or refractory (R/R) hairy cell leukaemia (HCL) who had received at minimum two prior systemic therapies, of which one a purine nucleoside analogue (PNA).
On the 11th of September 2018, the FDA updated the label of venetoclax tablets (VENCLEXTA®, Abbvie) in combination with rituximab (MabThera®, Roche) to include information about pre-treated patients with chronic lymphocytic leukemia (CLL) in the Phase III MURANO trial who had achieved Minimal Residual Disease (MRD)-negativity.
TOKYO and MUNICH and BASKING RIDGE, N.J., September 11, 2018 — The Japan Ministry of Health, Labour and Welfare (MHLW) has granted quizartinib (AC220, Daiichi Sankyo), an investigational inhibitor of FLT3, the Orphan Drug designation for the treatment of acute myeloid leukaemia (AML) harbouring FLT3-mutations.
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).
Single-agent PARP-inhibition with talazoparib is associated with an improved progression-free survival (PFS) and better patient-reported outcomes (PRO) when compared to chemotherapy alone in patients with advanced breast cancer (ABC) and a germline BRCA1/2 mutation, as reported by the investigators of the Phase III EMBRACA study (NCT01945775) in the New England Journal of Medicine.
On August 16, 2018 the FDA approved lenvatinib (Lenvima®, Eisai) for the first-line treatment of hepatocellular carcinoma (HCC) patients not amenable for curative surgery.
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.
On July 20, 2018, the US FDA approved ivosidenib (Tibsovo©, Agios Pharmaceuticals) for use in adult patients with relapsed or refractory acute myeloid leukaemia (AML) harbouring a susceptible IDH1 mutation as detected by an FDA-approved companion diagnostic (CDx) test, the Abbott RealTime IDH1 Assay.
On July 18, 2018, the US FDA expanded the ribociclib (Kysqali©, Novartis) approval. Ribociclib plus an aromatase inhibitor as initial endocrine-based therapy is no longer limited to postmenopausal HR-positive, HER2-negative advanced or metastatic breast cancer patients alone and now includes pre- and perimenopausal women. Furthermore, the FDA has added the combination ribociclib plus fulvestrant as initial endocrine-based therapy for postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer.
On June 27th, the FDA approved Array Biomarpharma’s combination encorafenib (BRAFTOVI®) plus binimetinib (and MEKTOVI®) for patients with unresectable or metastatic melanoma harbouring a BRAF V600E or V600K mutation detected by an FDA-approved test.
Non-small cell lung cancer (NSCLC): a key feature of the American Society of Clinical Oncology (ASCO) 2018 annual meeting. This year, encouraging results with single-agent immunotherapy (I-O) and combinations of I-O with chemotherapy (CTx), including the CheckMate 227 with nivolumab (NIVO), IMpower131 and IMpower150 studies with atezolizumab (ATEZO), and KEYNOTE-042 and KEYNOTE-407 studies with pembrolizumab (PEMBRO). Furthermore, important Asian data on treatments for epidermal growth-factor recptor (EGFR) mutation-positive (mu+) NSCLC (ARCHER 1050, NEJ009, NEJ026, and JO25567).
Breast cancer: a front-runner when it comes to the development of novel therapeutic strategies. With the advent of newer targeted- and immunotherapies, oncologists have an increment of options to offer their patients. The American Society of Clinical Oncology’s (ASCO) 2018 Breast Cancer track offered an extensive look at the latest advancements and updates from on-going trials covering the various subtypes of breast cancer.
- On June 13, 2018, the FDA approved bevacizumab (AvastinⓇ, Genentech, Inc.) in combination with carboplatin and paclitaxel, followed by single-agent bevacizumab for use after surgical resection in patients with stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer.
This year’s American Society of Clinical Oncology (ASCO) annual meeting includes two Phase III studies in the second-line treatment of the disease. Moreover, data with several immune-checkpoint inhibitors were presented, including the KEYNOTE-224 with pembrolizumab. Welcome to the summary of the ASCO 2018 HCC track.
- FDA granted regular approval to venetoclax (VENCLEXTA, AbbVie Inc. and Genentech Inc.) for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy.
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.
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.
On September 22, 2017, the Food and Drug Administration granted accelerated approval to nivolumab (OPDIVO, Bristol-Myers Squibb Co.) for the treatment of hepatocellular carcinoma (HCC) in patients who have been previously treated with sorafenib. Approval was based on a 154-patient subgroup of CHECKMATE-040 (NCT 01658878), a multicenter, open-label trial conducted in patients with HCC and […]
At the American Association for Cancer Research, 2014 annual meeting (AACR) Richard Finn presented the results of the PALOMA-1 study with Ibrance® (palbociclib), an oral inhibitor of cyclin-dependent kinase 4/6 (CDK4/6). Based on the results of this Phase 2 study, palbociclib was recently approved by the United States Drug and Food Administration (U.S. FDA). What is the current level of evidence on palbociclib in approved indications?
Recent studies have shown new possible applications for Ki67. Huh et al. showed that low Ki67 levels in healthy breast tissue correlated with a lesser lifetime chance of breast cancer. Another study by Arnedos and colleagues concluded that palbociclib was able to invoke a significant Ki67-level drop. After a decade of Ki67-controversies, these results put the marker back in the spotlight.
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