Sino Biological - 공식 웹사이트

Targeted Therapy Drugs

Why is Targeted Therapy Recommended

The superiority of targetd therapy compared with chemotherapy make it a star in cancer therapy research. So a lot of researches have been conducted in this area. Many researches have achieved good results and steppped into clinical sections. Furthermore, some of the drugs have been approved by FDA, leading to great significances in cancer therapy.

Elotuzumab Targeted Therapy

What is Elotuzumab? Elotuzumab, developed by Bristol-Myers Squibb, is a humanized monoclonal immunoglobulin G1 antibody targeting SLAMF7, which can be found on the surface of myeloma cells and natural killer lymphocytes in the immune system. It is approved on November 30, 2015 by the U.S. Food and Drug Administration for treating people with multiple myeloma who have received one to three prior medications in combination with two other therapies.

Target information of Elotuzumab

The target of this drug is SLAMF7. SLAMF7 is a glycosylated cell surface protein and a member of the SLAM (signaling lymphocyte activation molecules) family. It was first identified on NK cells, mediating their adhesion and function through a self-ligand binding interaction. Self-engagement of SLAMF7, or engagement by SLAMF7-specific antibodies, leads to association with its adaptor protein (EAT-2), resulting in enhanced activation of NK cells, promoting their ability to mediate killing of target cells through the subsequent release of cytotoxic granules. SLAMF7 is highly expressed in benign and neoplastic plasma cells, expressed at lower levels on the surface of NK cells, is infrequently expressed in the parenchyma of any major organs and is not found on hematopoietic stem cells, making it a unique protein for the therapeutic targeting of multiple myeloma cells.

What disease does Elotuzumab treat

Elotuzumab is applied for treating multiple myeloma. Multiple myeloma is a neoplasm that results in the accumulation of monoclonal plasma cells, predominantly in the bone marrow, which interfere with the production of normal white blood cells, red blood cells and platelets. It is the second most common hematological cancer after lymphoma, with an estimated incidence rate of 8 per 100,000 people and an estimated mortality rate of 2.2 per 100,000 people in Europe in 2012. Multiple myeloma remains largely incurable using current treatment approaches with fewer than 50% of patients surviving five years after diagnosis.

Efficacy of Elotuzumab

The approval of Elotuzumab was based on a multicenter, randomized, open-label, controlled trial evaluating progression-free survival (PFS) and overall response rate (ORR) in patients with relapsed or refractory multiple myeloma who had received 1 to 3 prior lines of therapy. A total of 646 patients were randomized (1:1) to receive elotuzumab in combination with lenalidomide and dexamethasone (n=321) or lenalidomide plus dexamethasone alone (n=325). Patients continued treatment until disease progression or the development of unacceptable toxicity.

The trial demonstrated a statistically significant improvement in both PFS and ORR, the trial's co-primary endpoints. The median PFS was 19.4 months in the elotuzumab-containing arm and 14.9 months in the lenalidomide plus dexamethasone alone arm (hazard ratio 0.70, 95% CI: 0.57, 0.85; p = 0.0004). The ORR in the elotuzumab-containing arm was 78.5% (95% CI: 73.6, 82.9) compared to 65.5% (95% CI: 60.1, 70.7) in the lenalidomide plus dexamethasone alone arm (p=0.0002).

Side effects of Elotuzumab

The safety data reflect exposure in 318 patients to elotuzumab in combination with lenalidomide and dexamethasone and 317 patients to lenalidomide plus dexamethasone. The most common adverse reactions (greater than or equal to 20%), with an increased rate in the elotuzumab arm compared to the control arm, were fatigue, diarrhea, pyrexia, constipation, cough, peripheral neuropathy, nasopharyngitis, upper respiratory tract infection, decreased appetite, and pneumonia.

Other important adverse reactions include infusion reactions, infections, second primary malignancies, hepatotoxicity, and interference with determination of complete response. As elotuzumab is an IgG kappa monoclonal antibody, it can be detected in the serum protein electrophoresis and immunofixation assays used to assess response.

Serious adverse events occurred in 65.4% of patients in the elotuzumab-containing arm compared to 56.5% in the lenalidomide plus dexamethasone alone arm. The most common serious adverse reactions were pneumonia, pyrexia, respiratory tract infection, anemia, pulmonary embolism, and acute renal failure.

Necitumumab Targeted Therapy

Necitumumab, developed by Eli Lilly, is a recombinant human IgG1 monoclonal antibody that binds to the human epidermal growth factor receptor (EGFR) and blocks the binding of EGFR to its ligands. It is applied in combination with gemcitabine and cisplatin for first-line treatment of patients with metastatic squamous non-small cell lung cancer (NSCLC).

Target information of Necitumumab

The target of this drug is EGFR. EGFR belongs to a family of receptor tyrosine kinases (TKs) that includes EGFR, ERBB2 (also known as HER2), ERBB3 (also known as HER3) and ERBB4 (also known as HER4). Structurally, each receptor is composed of an extracellular ligand-binding domain, a transmembrane domain and an intracellular domain. All family members have intrinsic TK activity, except ERBB3. The receptors exist as inactive monomers. On binding to ligands, such as EGF and transforming growth factor-α, the receptors undergo conformational changes that facilitate homodimerization or heterodimerization. Growth factor-induced receptor dimerization of EGFR is followed by intermolecular autophosphorylation of key tyrosine residues in the activation loop of catalytic TK domains through the transfer of γ-phosphates from bound adenosine triphosphate (ATP). Subsequently, appropriate adaptor or signalling molecules with SRC homology 2 and protein tyrosine-binding domains bind to carboxy-terminal phosphotyrosines and recruit proteins involved in downstream signalling events that control multiple cellular processes, including proliferation and survival. Selective blockade of EGFR and ERBB2 has been shown to be an effective therapeutic approach against multiple epithelial cancers.

What disease does Necitumumab treat

Necitumumab is applied for treating metastatic squamous non-small cell lung cancer (NSCLC). Lung cancer is the leading cause of cancer death in the United States. NSCLC, as the main type of this cancer can be divided into squamous cell and non-squamous cell cancer. Today, further subcategrization can be handled due to the various molecular criteria, which can also be regarded as a strategy for cancer treatment. The distinct subsets of cancer may have some driving mutations in genes that encode proteins are crucial for the cellular proliferation and survival. Targeting the activity of these mutant proteins can lead to cell death and therapeutic benefit. NSCLC harbours activating mutations in the epidermal growth factor receptor (EGFR) gene. So the EGFR protein act as a vital target in NSCLC therapy.

Efficacy of Necitumumab

The safety and efficacy of Necitumumab were evaluated in a multicenter, randomized, open-label clinical study of 1,093 participants with advanced squamous NSCLC who received the chemotherapies gemcitabine and cisplatin with or without Portrazza. Those taking Necitumumab plus gemcitabine and cisplatin lived longer on average (11.5 months) compared to those only taking gemcitabine and cisplatin (9.9 months). Necitumumab was not found to be an effective treatment in patients with non-squamous NSCLC.

Side effects of Necitumumab

The most common side effects of Necitumumab are skin rash and magnesium deficiency (hypomagnesemia), which can cause muscular weakness, seizure, irregular heartbeats and can be fatal. Necitumumab includes a boxed warning to alert health care providers of serious risks of treatment with Necitumumab, including cardiac arrest and sudden death, as well as hypomagnesemia.

Daratumumab Targeted Therapy

Daratumumab, jointly developed by Genmab along with the Johnson & Johnson subsidiary Janssen Biotech, by bingding to CD38 is the first monoclonal antibody approved for the treatment of multiple myeloma. It is administered as a single agent for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.

Target information of Daratumumab

The target of this drug is CD38. CD38 is a 46-kDa type II transmembrane glycoprotein with a short 20-aa N-terminal cytoplasmic tail and a long 256-aa extracellular domain. Functions ascribed to CD38 include receptor-mediated adhesion and signaling events, as well as important bifunctional ectoenzymatic activities that contribute to intracellular calcium mobilization. Under normal conditions, CD38 is expressed at relatively low levels on lymphoid and myeloid cells and in some tissues of nonhematopoietic origin. The relatively high expression of CD38 on all malignant cells in multiple myeloma in combination with its role in cell signaling suggest CD38 as a potential therapeutic Ab target for the treatment of multiple myeloid.

What disease does Daratumumab treat

Daratumumab is applied for treating multiple myeloid. Multiple myeloma is a neoplasm that results in the accumulation of monoclonal plasma cells, predominantly in the bone marrow, which interfere with the production of normal white blood cells, red blood cells and platelets. It is the second most common hematological cancer after lymphoma, with an estimated incidence rate of 8 per 100,000 people and an estimated mortality rate of 2.2 per 100,000 people in Europe in 2012. Multiple myeloma remains largely incurable using current treatment approaches with fewer than 50% of patients surviving five years after diagnosis. Therefore, new approaches that induce long-term tumor regression and improve disease outcome are needed and urgently sought for.

Efficacy of Daratumumab

The safety and efficacy of Daratumumab were demonstrated in two open-label studies. In one study of 106 participants receiving Daratumumab, 29 percent of patients experienced a complete or partial reduction in their tumor burden, which lasted for an average of 7.4 months. In the second study of 42 participants receiving Daratumumab, 36 percent had a complete or partial reduction in their tumor burden.

Side effects of Daratumumab

The most common side effects of Daratumumab were infusion-related reactions, fatigue, nausea, back pain, fever and cough. Daratumumab may also result in low counts of infection-fighting white blood cells (lymphopenia, neutropenia, and leukopenia) or red blood cells (anemia) and low levels of blood platelets (thrombocytopenia).

Ramucirumab Targeted Therapy

Ramucirumab, developed by Eli Lilly, a recombinant monoclonal antibody of the IgG1 class that binds to vascular endothelial growth factor receptor-2 (VEGFR-2) and blocks the activation of the receptor. It is approved for the treatment of multiple sollid tumors: metastatic colorectal cancer, platinum-resistant metastatic non-small cell lung cancer, advanced gastric or gastroesophageal junction adenocarcinoma and gastric or gastroesophageal junction adenocarcinoma.

Target information of Ramucirumab

The target of this drug is VEGFR2. VEGFR2 is largely considered the primary VEGF family receptor driving angiogenesis. A critical pillar of angiogenesis is the interaction of the VEGF family of pro-angiogenic cytokines and their respective receptors. The VEGF family includes VEGFA, VEGFB, VEGFC, VEGFD, VEGFE, and placental growth factor (PlGF) with three receptors: VEGFR1, VEGFR2, and VEGFR3 with associated co-reptors neuropillin 1 and 2. VEGFR2 expression is typically limited to vessel endothelial cells and binds VEGFA, VEGFE and processed forms of VEGFC and VEGFD. VEGFR2 is widely considered the main receptor driving angiogenesis. Upregulation of VEGFR2 expression is seen in the tumor vasculature in a variety of malignancies.

What disease does Ramucirumab treat

In 2014, Ramucirumab is appproved for use in combination with paclitaxel for the treatment of patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma and as a single agent for the treatment of patients with advanced gastric or GEJ adenocarcinoma refractory to or progressive following first-line therapy with platinum or fluoropyrimidine chemotherapy. And it is appproved for use in combination with docetaxel for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with disease progression on or after platinum-based chemotherapy. In 2015, Ramucirumab is applied for use in combination with FOLFIRI for the treatment of patients with metastatic colorectal cancer (mCRC) whose disease has progressed on a first line bevacizumab-, oxaliplatin- and fluoropyrimidine-containing regimen.

Efficacy of Ramucirumab

For metastatic colorectal cancer: the clinical trial accrued 1072 patients who were randomly allocated (1:1) to receive FOLFIRI plus placebo or FOLFIRI plus ramucirumab (N=536 per arm). Treatment cycles on both arms were repeated every 2 weeks and ramucirumab was administered at a dose of 8 mg/kg by intravenous infusion every two weeks. Ramucirumab was continued until disease progression or unacceptable toxicity.
The primary efficacy endpoint was overall survival (OS). Treatment assignment was stratified by geographic region (North America vs. Europe vs. other regions), KRAS status (wild-type vs. mutant) and time to progression for the beginning of first-line treatment (< 6 months vs. greater than or equal to 6 months).

The median age of the study population was 62 years, 57% were men, and 99% had an ECOG performance status of 0 or 1. A statistically significant OS improvement was observed in patients receiving FOLFIRI plus ramucirumab compared to those receiving FOLFIRI plus placebo [HR 0.85 (95% CI: 0.73, 0.98), p=0.023, stratified log-rank test]. Median OS was 13.3 and 11.7 months for patients on the FOLFIRI plus ramucirumab and FOLFIRI plus placebo arms, respectively. PFS was also significantly improved in patients who received ramucirumab in combination with FOLFIRI [HR 0.79 (95% CI: 0.70, 0.90), p<0.001]. Median PFS was 5.7 and 4.5 months, respectively.

For platinum-resistant metastatic non-small cell lung cancer: the approval of ramucirumab in combination with docetaxel in NSCLC was based on the demonstration of improved overall survival (OS) in a multicenter, double-blind, placebo-controlled study (I4T-MC-JVBA) that enrolled 1253 patients with previously treated metastatic NSCLC. Patients were randomized to receive either ramucirumab (10 mg/kg every three weeks) in combination with docetaxel (75 mg/m2 every 3 weeks) on day 1 of a 21-day cycle (n=628) or matching placebo plus docetaxel (n=625).

A statistically significant prolongation of OS was demonstrated [HR 0.86; (95% CI: 0.75, 0.98); p=0.024]; median OS was 10.5 months in the ramucirumab plus docetaxel arm and 9.1 months in the placebo plus docetaxel arm. Progression-free survival was also significantly longer for patients receiving ramucirumab plus docetaxel [HR=0.76 (95% CI: 0.68, 0.86); p<0.001)].

For advanced gastric or gastroesophageal junction adenocarcinoma: the approval of ramucirumab in combination with paclitaxel was based on the demonstration of improved overall survival (OS) in a multicenter, double-blind, placebo-controlled study (I4T-IE-JVBE) that enrolled 665 patients with previously-treated advanced or metastatic gastric or GEJ adenocarcinoma. Patients were randomized to receive either ramucirumab (8 mg/kg every two weeks) in combination with paclitaxel (80 mg/m2 once a week for 3 weeks of every 28-day cycle) (n=330) or matching placebo plus paclitaxel (n=335).

A statistically significant prolongation of OS was demonstrated [HR 0.81; (95% CI: 0.68, 0.96); p=0.017]; median OS was 9.6 and 7.4 months in the ramucirumab plus paclitaxel arm and placebo plus paclitaxel arm, respectively. Progression-free survival was also significantly longer for patients receiving ramucirumab plus paclitaxel [HR=0.64 (95% CI: 0.54, 0.75); p<0.001)].

Side effects of Ramucirumab

For advanced gastric or gastroesophageal junction adenocarcinoma: safety data was evaluated in 656 patients who received at least one dose of study drug. The most frequently reported adverse reactions with ramucirumab plus paclitaxel (incidence greater than or equal to 30%) were fatigue/asthenia, neutropenia, diarrhea, and epistaxis. The most common serious adverse reactions with ramucirumab plus paclitaxel were neutropenia and febrile neutropenia (3.7% and 2.4%, respectively).

For platinum-resistant metastatic non-small cell lung cancer: safety data was evaluated in 1245 patients who received at least one dose of study drug. The most frequently reported adverse reactions with ramucirumab plus docetaxel (incidence greater than or equal to 30%) were neutropenia, fatigue/asthenia, and stomatitis/mucosal inflammation. The most common serious adverse reactions with ramucirumab plus docetaxel were febrile neutropenia (14%), pneumonia (6%), and neutropenia (5%).

For metastatic colorectal cancer: in general, the safety data was consistent with the known safety profile established in previously approved indications. However, thyroid dysfunction (hypothyroidism) was reported in 2.6% of patients based on thyroid monitoring in patients with mCRC.

Trastuzumab Targeted Therapy

Trastuzumab, developed by Genentech, Inc., a monoclonal antibody that interferes with the HER2/neu receptor. It is approved in combination with cisplatin and a fluoropyrimidine (capecitabine or 5-fluorouracil), for the treatment of patients with HER2 overexpressing metastatic gastric or gastroesophageal (GE) junction adenocarcinoma, who have not received prior treatment for metastatic disease.

Target information of Trastuzumab

The target of this drug is HER2/neu receptor. The HER receptors are proteins that are embedded in the cell membrane and communicate molecular signals from outside the cell (molecules called EGFs) to inside the cell, and turn genes on and off. The HER protein, Human Epidermal Growth Factor Receptor, binds to Human Epidermal Growth Factor, and stimulates cell proliferation. In some cancers, notably certain types of breast cancer, HER2 is over-expressed, and causes cancer cells to reproduce uncontrollably.

What disease does Trastuzumab treat

The approval is based on a significant improvement in median overall survival (OS) of 2.5 months with trastuzumab plus chemotherapy treatment compared to chemotherapy alone demonstrated in a single, international, multicenter, open-label, randomized clinical trial, BO18255 (ToGA trial). A total of 594 patients with locally advanced or metastatic HER2 overexpressing adenocarcinoma of the stomach or GE junction were randomized (1:1) to receive either trastuzumab plus chemotherapy or chemotherapy alone.

The trial was closed after the second interim analysis when 167 deaths had occurred on the trastuzumab arm and 184 deaths on the control arm. In the final OS analysis, the median OS was 13.5 months (95% CI: 11.7, 15.7) and 11.0 months (95% CI: 9.4, 12.5) in the trastuzumab and control arms, respectively. The hazard ratio (HR) was 0.73 [(95% CI: 0.60, 0.91); p-value, two sided = 0.0038 (nominal significance level of 0.0193)] in favor of the trastuzumab arm.

Efficacy of Trastuzumab

The approval is based on a significant improvement in median overall survival (OS) of 2.5 months with trastuzumab plus chemotherapy treatment compared to chemotherapy alone demonstrated in a single, international, multicenter, open-label, randomized clinical trial, BO18255 (ToGA trial). A total of 594 patients with locally advanced or metastatic HER2 overexpressing adenocarcinoma of the stomach or GE junction were randomized (1:1) to receive either trastuzumab plus chemotherapy or chemotherapy alone.

The trial was closed after the second interim analysis when 167 deaths had occurred on the trastuzumab arm and 184 deaths on the control arm. In the final OS analysis, the median OS was 13.5 months (95% CI: 11.7, 15.7) and 11.0 months (95% CI: 9.4, 12.5) in the trastuzumab and control arms, respectively. The hazard ratio (HR) was 0.73 [(95% CI: 0.60, 0.91); p-value, two sided = 0.0038 (nominal significance level of 0.0193)] in favor of the trastuzumab arm.

Side effects of Trastuzumab

The most common adverse reactions (< 10%) associated with trastuzumab were neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia. The most common grade 3 and 4 adverse reactions (>5%) related to trastuzumab were neutropenia (35%), anemia (12%), diarrhea (9%), nausea (8%), anorexia (7%), and vomiting (6%). About 37% of patients receiving trastuzumab plus chemotherapy had infusion-related reactions. No grade 4 infusion reactions or deaths related to infusion reactions were reported. Cardiac adverse reactions occurred at the same incidence on both study arms. The incidence of cardiac failure was < 1%. Over 90% of the deaths in both arms were due to disease progression or disease-related complications. The most common adverse reactions resulting in treatment discontinuation in the trastuzumab arm were infection, diarrhea, and febrile neutropenia.

Vemurafenib Targeted Therapy

Vemurafenib, developed by Hoffmann-La Roche Inc., a B-Raf enzyme inhibitor. It is approved for the treatment of patients with unresectable or metastatic melanoma with the BRAF V600E mutation as detected by an FDA-approved test.

Target information of Vemurafenib

The target of this drug is BRAF. BRAF belongs to a family of serine-threonine protein kinases that includes ARAF, BRAF, and CRAF (RAF1). RAF kinases are central mediators in the MAP kinase signaling cascade and exert their effect predominantly through phosphorylation and activation of MEK. This occurs following the dimerization (hetero- or homo-) of the RAF molecules. As part of the MAP kinase pathway, RAF is involved in many cellular processes, including cell proliferation, differentiation, and transcriptional regulation.

Efficacy of Vemurafenib

The approval was based primarily on an international, randomized, open-label trial in patients with previously untreated metastatic or unresectable melanoma with the BRAFV600E mutation. The trial enrolled 675 patients; 337 patients were assigned to vemurafenib, 960 mg orally twice daily, and 338 were assigned to dacarbazine, 1000 mg/m2 intravenously, every three weeks. Treatment continued until disease progression, unacceptable toxicity, and/or consent withdrawal. The median follow-up at the time of the overall survival analysis was 6.2 and 4.5 months for the vemurafenib and dacarbazine arms, respectively. Overall survival was significantly improved in patients receiving vemurafenib compared to those receiving dacarbazine (HR=0.44; 95% CI: 0.33, 0.59; p< 0.0001, log-rank test). The median survival of patients receiving vemurafenib had not been reached (95% CI: 9.6 months, not reached) and was 7.9 months (95% CI: 7.3, 9.6) for those receiving dacarbazine. Progression-free survival (PFS) was also significantly improved in patients receiving vemurafenib (HR=0.26; 95% CI: 0.20, 0.33; p<0.0001, log-rank test). The median PFS was 5.3 (95% CI: 4.9, 6.6) and 1.6 months (95% CI: 1.6, 1.7) in the vemurafenib and dacarbazine arms, respectively. Overall response rate (complete plus partial response rates) was 48.4% (95% CI: 41.6%, 55.2%) and 5.5% (95% CI: 2.8%, 9.3%) in the vemurafenib and dacarbazine arms, respectively.

Side effects of Vemurafenib

The most common adverse reactions (≥30%) in patients treated with vemurafenib were arthralgia, rash, alopecia, fatigue, photosensitivity reaction, and nausea. Cutaneous squamous cell carcinomas (cuSCC), including squamous cell carcinomas of the skin and keratoacanthomas, were detected in approximately 24% of patients treated with vemurafenib. CuSCCs were managed with excision in clinical trials, and patients were able to continue treatment without dose adjustment. Other adverse reactions, sometimes severe, reported in vemurafenib-treated patients included hypersensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, uveitis, QT prolongation, and liver enzyme laboratory abnormalities.

Crizotinib Targeted Therapy

Crizotinib, developed by Pfizer, Inc., a targted therapy drug for both ALK and ROS1. It is approved to treat patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are ROS1-positive in 2016. And in 2013 it is also indicated for patients with metastatic NSCLC whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test.

Target information of Crizotinib

The target of this drug is ROS1 and ALK. ROS1 is a receptor tyrosine kinase (RTK) of the insulin receptor family. ROS1 fusions contain an intact tyrosine kinase domain. To date, those tested biologically possess oncogenic activity. Signaling downstream of ROS1 fusions results in activation of cellular pathways known to be involved in cell growth and cell proliferation. ROS1 fusions are associated with sensitivity in vitro to tyrosine kinase inhibitors that inhibit ROS1. The anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that is aberrant in a variety of malignancies. The various N-terminal fusion partners promote dimerization and therefore constitutive kinase activity. Signaling downstream of ALK fusions results in activation of cellular pathways known to be involved in cell growth and cell proliferation.

Efficacy of Crizotinib

An open-label, active-controlled, multinational, randomized trial enrolled 347 patients with ALK-positive, metastatic NSCLC. Patients were required to have progressed following platinum-based chemotherapy and to have ALK expression in tumor specimens detected by fluorescence in situ hybridization on central laboratory testing. Patients were randomized to receive either crizotinib 250 mg orally twice daily (n=173) or chemotherapy (n=174). Patients randomized to chemotherapy received pemetrexed (58%) or docetaxel (42%) if they had received prior pemetrexed. Approximately 64% of patients on the chemotherapy arm subsequently received crizotinib.
The trial demonstrated significantly prolonged progression-free survival (PFS) for crizotinib treatment compared to chemotherapy [HR=0.49, (95% CI: 0.37, 0.64), p<0.0001]. Median PFS was 7.7 and 3.0 months on the crizotinib and chemotherapy arms, respectively. The ORR was significantly higher for the crizotinib arm (65% vs. 20%) with median response durations of 7.4 and 5.6 months in the crizotinib and chemotherapy arms, respectively. No difference in overall survival was noted between the two arms [HR= 1.02 (95% CI: 0.68, 1.54)] in a planned interim analysis.

Side effects of Crizotinib

Common adverse reactions in clinical trials with crizotinib, occurring at an incidence of 25% or higher, included visual disorders, nausea, diarrhea, vomiting, constipation, edema, elevated transaminases, and fatigue.

Safety data from this trial was evaluated in 172 crizotinib-treated patients. Serious adverse events were reported in 37% of crizotinib-treated patients. The most common serious adverse reactions of crizotinib were pneumonia, pulmonary embolism, dyspnea, and interstitial lung disease. Fatal adverse reactions occurred in 9 crizotinib-treated patients and included acute respiratory distress syndrome, arrhythmia, dyspnea, pneumonia, pneumonitis, pulmonary embolism, interstitial lung disease, respiratory failure, and sepsis.

References

1. Palumbo A, Sonneveld P, Palumbo A. Preclinical and Clinical Evaluation of Elotuzumab, a SLAMF7-targeted Humanized Monoclonal[J].
2. Pao W, Chmielecki J. Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer[J]. Nature Reviews Cancer, 2010, 10(11): 760-774.
3. De Weers M, Tai Y T, van der Veer M S, et al. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors[J]. The Journal of Immunology, 2011, 186(3): 1840-1848.
4. Clarke J et al. Targeted inhibition of VEGF Receptor-2: An update on Ramucirumab. Expert opinion on biological therapy. 2013;13(8):1187-1196. doi:10.1517/14712598.2013.810717.