Tag: General Medical Oncology & Hematology

Tumor genomic profiling enables the identification of specific genomic alterations and thereby can provide personalized treatment options with targeted therapies that are specific for those molecular targets. Next-Generation Sequencing (NGS) platforms or second-generation sequencing perform massively parallel sequencing, which allows sequencing of millions of fragments of DNA from a single sample. Recently reported genomic profiling studies performed in patients with advanced cancer suggest that actionable mutations are found in 20-40% of patients’ tumors.
Larotrectinib is a potent and highly selective small molecule inhibitor of three TRK proteins, Tropomyosin Receptor Kinase genes NTRK1, NTRK2, and NTRK3. In a phase I-II study involving children, adolescents and adults with 17 unique cancer diagnoses, the Overall Response Rate was 75% and at 1 year, 71% of the responses were ongoing and 55% of the patients remained progression-free. It was concluded from this study that TRK fusions defined a unique molecular subgroup of advanced solid tumors in children and adults and Larotrectinib had marked and durable antitumor activity in patients with TRK fusion-positive cancer, regardless of the age of the patient or tumor type.

SUMMARY: Tumor genomic profiling enables the identification of specific genomic alterations and thereby can provide personalized treatment options with targeted therapies that are specific for those molecular targets. The FDA in May 2017, granted accelerated approval to KEYTRUDA® (Pembrolizumab), for adult and pediatric patients with unresectable or metastatic, MicroSatellite Instability-High (MSI-H) or MisMatch Repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options. This is the first FDA approval of a systemic cancer treatment, based on a specific genetic biomarker, independent of tumor origin (first tissue/site-agnostic approval).

A genomic test can be performed on a tumor specimen or on cell-free DNA in plasma (“liquid biopsy”) or an ImmunoHistoChemistry (IHC) test can be performed on tumor tissue for protein expression that demonstrates a genomic variant known to be a drug target, or to predict sensitivity to a chemotherapeutic drug. Next-generation sequencing (NGS) platforms or second-generation sequencing unlike the first-generation sequencing, known as Sanger sequencing, perform massively parallel sequencing, which allows sequencing of millions of fragments of DNA from a single sample. With this high-throughput sequencing, the entire genome can be sequenced in less than 24 hours. Recently reported genomic profiling studies performed in patients with advanced cancer suggest that actionable mutations are found in 20-40% of patients’ tumors.

The molecules of interest are Neurotrophic Tropomyosin Receptor Kinase (NTRK) gene rearrangements. The three TRK family of Tropomyosin Receptor Kinase (TRK) transmembrane proteins TRKA, TRKB, and TRKC are encoded by Neurotrophic Tropomyosin Receptor Kinase genes NTRK1, NTRK2, and NTRK3, respectively. These receptor tyrosine kinases are expressed in human neuronal tissue and are involved in a variety of signaling events such as cell differentiation, cell survival and apoptosis of peripheral and central neurons. They therefore play an essential role in the physiology of development and function of the nervous system. Chromosomal fusion involving NTRK genes represent the main molecular alterations with known oncogenic and transforming potential and have been identified in a variety of cancers both in children and adults. Gene fusions involving NTRK genes lead to transcription of chimeric TRK proteins which can confer oncogenic potential by increasing cell proliferation and survival. These genetic abnormalities have generated a lot of interest and have emerged as targets for cancer therapy. NGS has allowed the discovery of these gene fusions. Early clinical evidence suggests that these gene fusions lead to oncogene addiction regardless of tissue of origin. (Oncogene addiction is the dependency of some cancers on one or a few genes for the maintenance of the malignant phenotype).

Larotrectinib is a potent and highly selective small molecule inhibitor of all three TRK proteins. The authors in this development program included patients of any age and with any tumor type who had chromosomal fusion involving NTRK genes (Age and Tumor agnostic therapy). This program enrolled 55 patients, ranging in age from 4 months to 76 years, with consecutively and prospectively identified TRK fusion-positive cancers, detected by molecular profiling. They were assigned to three clinical studies – a phase I study involving adults, a phase I-II study involving children and a phase II study involving adolescents and adults.

This population of patients encompassed 17 unique cancer diagnoses and enrolled patients had locally advanced or metastatic solid tumors, and had received prior standard therapy (if available). The Primary end point for the combined analysis was the Overall Response Rate according to Independent review. Secondary end points included Duration of Response, Progression Free Survival, and safety. The researchers in this publication reported the safety and efficacy analysis of the first 55 consecutively enrolled patients, identified with TRK fusion-positive cancers, treated across these studies.

The Overall Response Rate was 75%. A total of 13% of the patients had a Complete Response, 62% had a Partial Response and 13% had stable disease. The median Duration of Response and Progression Free Survival had not been reached. At a median follow-up of 9.4 months, 86% of the patients with a response continued treatment or had undergone curative surgery. At 1 year, 71% of the responses were ongoing and 55% of the patients remained progression-free. The most common adverse events of any grade were fatigue, vomiting and abnormal liver function studies. None of the patients on Larotrectinib discontinued therapy due to a drug-related adverse event.

It was concluded that TRK fusions defined a unique molecular subgroup of advanced solid tumors in children and adults and Larotrectinib had marked and durable antitumor activity in patients with TRK fusion-positive cancer, regardless of the age of the patient or tumor type. Efficacy of Larotrectinib in TRK Fusion–Positive Cancers in Adults and Children. Drilon A, Laetsch TW, Kummar S, et al. N Engl J Med 2018; 378:731-739

SUMMARY: The ASCO convened an Expert Panel and updated evidence-based guidance on the use of platelet transfusion in patients with cancer. This guideline updates is based on a systematic review of the medical literature published from September 1, 2014, through October 26, 2016 and this review builds on two 2015 systematic reviews that were conducted by the AABB and the International Collaboration for Transfusion Medicine Guidelines. This ASCO guideline replaces the previous ASCO platelet transfusion guideline published initially in 2001. The updated ASCO review included 24 more recent publications which included 3 clinical practice guidelines, 8 systematic reviews, and 13 observational studies.

Target Population: Adults and children (4 months of age or older) with hematologic malignancies, solid tumors, or hypoproliferative thrombocytopenia.

Target Audience: Clinician’s administering intensive therapies to patients with cancer.

Clinical Questions and Recommendations:

(1) How should platelets for transfusion be prepared?

Platelets can be prepared either by separation of units of platelet concentrates from whole blood using either the buffy coat or the platelet-rich plasma method, which can then be pooled before administration, or by apheresis from single donors. Studies have shown that the post-transfusion increments, hemostatic benefit, and adverse effects are similar with any of these platelet products and they can be used interchangeably. However, single-donor platelets from selected donors are necessary when histocompatible platelet transfusions are needed.

(2) In what circumstances should providers take steps to prevent Rh alloimmunization resulting from platelet transfusion?

Prevention of RhD alloimmunization resulting from platelet transfusions to RhD-negative recipients can be achieved either through the exclusive use of platelet products collected from RhD-negative donors or via anti-D immunoprophylaxis. These approaches may be used for female children and female adults of child-bearing potential being treated with curative intent. However, because of the low rate of RhD alloimmunization in patients with cancer, these approaches need not be applied universally.

(3) In what circumstances should providers use leukoreduced blood products to prevent alloimmunization?

Providing leukoreduced blood products to patients with Acute Myeloid Leukemia from the time of diagnosis is appropriate, as the incidence of alloantibody-mediated refractoriness to platelet transfusion can be decreased in patients receiving induction chemotherapy, when both platelet and RBC products are leukoreduced before transfusion. It is likely that alloimmunization can also be decreased in patients with other types of leukemia and in other patients with cancer who are receiving chemotherapy. The same holds true for patients with Aplastic Anemia, and Myelodysplasia not receiving chemotherapy, in the same time periods that the transfusions are being administered. In the United States and in several other countries, majority of blood products are leukoreduced at the time of blood collection and component preparation. Prestorage leukoreduction can result in a substantial reduction in transfusion reactions and in transmission of cytomegalovirus (CMV) infection

(4) Should platelet transfusions be given prophylactically or therapeutically?

Prophylactic platelet transfusion should be administered to patients with thrombocytopenia resulting from impaired bone marrow function to reduce the risk of hemorrhage, when the platelet count falls below a predefined threshold level. This threshold level for transfusion varies according to the patient’s diagnosis, clinical condition, and treatment modality.

(5) What is the appropriate threshold for prophylactic platelet transfusion in patients with hematologic malignancies?

The Panel recommends a threshold of less than 10×10⁹/L for prophylactic platelet transfusion in patients receiving therapy for hematologic malignancies. Transfusion at higher levels may be advisable in patients with signs of hemorrhage, high fever, hyperleukocytosis, rapid fall of platelet count, or coagulation abnormalities (eg, acute promyelocytic leukemia) and in those undergoing invasive procedures or in circumstances in which platelet transfusions may not be readily available in case of emergencies, as might be the case for outpatients who live at a distance from the treatment center.

(6) What is the appropriate threshold for prophylactic platelet transfusion in the setting of Hematopoietic Stem Cell Transplantation (HSCT)?

The Panel recommends a threshold of less than 10×10⁹/L for prophylactic platelet transfusion in adult and pediatric patients undergoing allogeneic HSCT. Prophylactic platelet transfusion may be administered at higher counts based on clinician judgment. In adult recipients of autologous HSCT, randomized trials have demonstrated similar rates of bleeding with decreased platelet usage when patients are transfused at the first sign of bleeding rather than prophylactically, and this approach may be used in experienced centers. This recommendation is not generalizable to pediatric patients.

(7) Is there a role for prophylactic platelet transfusion in patients with chronic, stable, severe thrombocytopenia who are not receiving active treatment?

Patients with chronic, stable, severe thrombocytopenia, such as individuals with Myelodysplasia or Aplastic Anemia, who are not receiving active treatment may be observed without prophylactic transfusion, reserving platelet transfusions for episodes of hemorrhage or during times of active treatment.

(8) What is the appropriate threshold for prophylactic platelet transfusion in patients with solid tumors?

The risk of bleeding in patients with solid tumors during chemotherapy-induced thrombocytopenia is related to the depth and duration of the platelet nadir, although other factors contribute as well. The Panel recommends a threshold of less than 10×10⁹/L for prophylactic platelet transfusion. Platelet transfusion at higher levels is appropriate in patients with active localized bleeding, which can sometimes be seen in patients with necrotic tumors.

(9) At what platelet count can surgical or invasive procedures be performed?

The Panel recommends a threshold of 40×10⁹/L to 50×10⁹/L for performing major invasive procedures in the absence of associated coagulation abnormalities. Certain procedures, such as bone marrow aspirations and biopsies, and insertion or removal of central venous catheters, can be performed safely at counts 20×10⁹/L or more. If platelet transfusions are administered before a procedure, it is critical that a post-transfusion platelet count be obtained to prove that the desired platelet count level has been reached. Platelet transfusions should also be available on short notice, in case intraoperative or postoperative bleeding occurs. For alloimmunized patients, histocompatible platelets must be available in these circumstances.

(10) When and how should patients be monitored for refractoriness to platelet transfusion?

The Panel recommends that when refractoriness is suspected, platelet counts should be performed 10-60 minutes after transfusion. Because patients may have a poor increment to a single transfusion and yet have excellent platelet increments with subsequent transfusions, a diagnosis of refractoriness to platelet transfusion should only be made when at least two transfusions of ABO-compatible units, stored for less than 72 hours, result in poor increments (less than 5000/microliter).

(11) How should refractoriness to platelet transfusion be managed?

Alloimmunization is usually due to antibody against HLA antigens and only rarely to platelet-specific antigens. Patients with alloimmune-refractory thrombocytopenia, as defined previously, are best managed with platelet transfusions from histocompatible donors matched for HLA-A and HLA-B antigens. For patients( 1) whose HLA type cannot be determined, (2) who have uncommon HLA types for whom suitable donors cannot be identified, or (3) who do not respond to HLA-matched platelets, histocompatible platelet donors can often be identified using platelet cross-matching techniques. In many patients, these two techniques are complementary.

Platelet Transfusion for Patients With Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. Schiffer CA, Bohlke K, Delaney M, et al. J Clin Oncol. 2017 Nov 28:JCO2017761734. doi: 10.1200/JCO.2017.76.1734. [Epub ahead of print]

SUMMARY: The FDA on November 30, 2017, granted marketing approval to FoundationOne CDx (F1CDx), a Next Generation Sequencing (NGS) based, in vitro diagnostic (IVD) assay, to detect genetic mutations in 324 genes and two genomic signatures, in any solid tumor type. The test can also identify which patients with Non Small Cell Lung Cancer (NSCLC), Melanoma, Breast cancer, ColoRectal cancer, or Ovarian cancer may benefit from 15 different FDA-approved targeted treatment options.

The basic premise of cancer genomics is that cancer is caused by somatically acquired mutations, and is therefore a disease of the genome. Tumor genomic profiling enables the identification of specific genomic alterations and thereby can provide personalized treatment options with targeted therapies that are specific for those molecular targets. A genomic test can be performed on a tumor specimen or on cell-free DNA in plasma (“liquid biopsy”) or an ImmunoHistoChemistry (IHC) test can be performed on tumor tissue for protein expression that demonstrates a genomic variant known to be a drug target, or to predict sensitivity to a chemotherapeutic drug.

Next-Generation Sequencing (NGS) platforms or second-generation sequencing, unlike the first-generation sequencing, known as Sanger sequencing, perform massively parallel sequencing, which allows sequencing of millions of fragments of DNA from a single sample. With this high-throughput sequencing, the entire genome can be sequenced in less than 24 hours. This is in contrast to Sanger sequencing technology which has required over a decade to decipher the human genome. There are a number of different NGS platforms using different sequencing technologies and NGS can be used to sequence and systematically study the cancer genomes in their entirety or specific areas of interest in the genome or small numbers of individual genes. Recently reported genomic profiling studies, performed in patients with advanced cancer suggest that actionable mutations are found in 20-40% of patients’ tumors.

The application for F1CDx , was reviewed by the FDA using a coordinated, cross-agency approach and clinical performance of the test was established by comparing F1CDx to previously FDA-approved companion diagnostic tests, that are currently used to determine patient eligibility for certain treatments. It was noted that F1CDx assay’s ability to detect select mutation types (substitutions and short insertions and deletions) representative of the entire 324 gene panel was accurate approximately 94.6% of the time. This 324 gene panel included EGFR, KRAS, BRAF, BRCA1/2, ALK, and several other genes with emerging therapies, such as NTRK1/2/3. This assay can additionally detect MicroSatellite Instability (MSI) and Tumor Mutational Burden, which can predict response to immunotherapy.

The FDA noted that this is the first device with the FDA’s “Breakthrough Device” designation to complete the PreMarket Approval (PMA) process, and it is the second IVD authorized under the FDA and Centers for Medicare & Medicaid Services’ (CMS) Parallel Review program. Under this program, the CMS issued a proposed national coverage determination of the F1CDx for Medicare beneficiaries with recurrent, metastatic, or advanced Stage IV cancer, who have not been previously tested using NGS technology, and who continue to remain candidates for further therapy. https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm587387.htm

Alcohol consumption is an established risk factor for several malignancies, and is a potentially modifiable risk factor for cancer. The International Agency for Research on Cancer (IARC), a branch of WHO, classified alcohol as a group 1 carcinogen. The American Heart Association, American Cancer Society, and US Department of Health and Human Services all recommend that men limit intake to one to two drinks per day and women to one drink per day. People who do not currently drink alcohol should not start for any reason. There is a clear association between alcohol and upper aerodigestive tract cancers (larynx, esophagus, and oral cavity/pharynx). A recent meta-analysis of cohort studies among 209,597 cancer survivors showed an 8% increase in overall mortality and a 17% increased risk for recurrence in the highest versus lowest alcohol consumers. The benefit of alcohol consumption on cardiovascular health likely has been overstated and the net effect of alcohol is harmful. Alcohol consumption should therefore not be recommended to prevent cardiovascular disease or all-cause mortality.

SUMMARY: It has been estimated that in the United States, 3-4% of all cancer deaths are attributable to drinking alcohol. According to the Centers for Disease Control and Prevention, approximately 88,000 deaths were attributed to excessive alcohol use in the United States between 2006 and 2010. Alcohol consumption is an established risk factor for several malignancies, and is a potentially modifiable risk factor for cancer. The International Agency for Research on Cancer (IARC), a branch of WHO, classified alcohol as a group 1 carcinogen. The Cancer Prevention Committee of the American Society of Clinical Oncology has now provided an overview of the evidence of the links between alcohol drinking and cancer risk and cancer outcomes.

DRINKING GUIDELINES AND DEFINITIONS

The American Heart Association, American Cancer Society, and US Department of Health and Human Services all recommend that men limit intake to one to two drinks per day and women to one drink per day. People who do not currently drink alcohol should not start for any reason. A standard drink is defined as one that contains roughly 14 g of pure alcohol, which is the equivalent of 1.5 ounces of distilled spirits, 5 ounces of wine or 12 ounces of regular beer. Moderate drinking is defined at up to one drink per day for women and up to 2 drinks per day for men whereas heavy drinking is defined as 8 or more drinks per week or 3 or more drinks per day for women, and as many as 15 or more drinks per week or 4 or more drinks per day for men. Hispanics and blacks have a higher risk than whites, for developing alcohol-related liver disease. Use of alcohol during childhood and adolescence is a predictor of increased risk of alcohol related disorders later in life.

ROLE OF ALCOHOL IN CARCINOGENESIS

Alcohol is predominantly metabolized in the liver to acetaldehyde, which is a carcinogen and is responsible for many “hangover” symptoms. Acetaldehyde is then converted into harmless acetic acid radicals also known as acetyl radicals, and eliminated from the body. There is strong evidence to suggest that acetaldehyde damages DNA. Acetaldehyde generated during alcohol metabolism in the human body is eliminated by Aldehyde Dehydrogenase-2 (ALDH2). However, a genetic variant of ALDH2, which is an inactive form, exists and individuals with the inactive form of ALDH2 who consume alcohol, accumulate excessive amounts of acetaldehyde, which in turn can lead to greater susceptibility to alcohol-induced cancer. It has been noted that this high-risk genotype in prevalent in about 50% of North East Asian population and in 5–10% of blond-haired blue-eyed people of Northern European descent. Alcohol consumption in this group is more strongly associated with cancers of the upper aerodigestive tract. Breast tissue is also more susceptible to alcohol than other sites. Even moderate alcohol intake has been associated with increased levels of circulating sex hormones, which in turn can activate cellular proliferation. Alcohol consumption is associated with lower serum folate concentrations and this may play a role in the etiology of colon cancer.

ALCOHOL AND CANCER

There is a clear association between alcohol and upper aerodigestive tract cancers (larynx, esophagus, and oral cavity/pharynx), as a result of direct contact of ingested alcohol with the involved tissues.

Continued alcohol use among survivors of upper aerodigestive tract cancers is associated with a 3 fold increase in the risk of a second primary tumor in the upper aerodigestive tract. Additionally, there is a synergistic interaction between alcohol consumption and cigarette smoking. Smoking and alcohol use during and after radiation therapy have been associated with an increased risk of osteoradionecrosis of the jaw, in patients with oral and oropharyngeal cancers.

Among women with Estrogen Receptor-positive breast cancer, those consuming 7 or more drinks per week have a 90% increased risk of asynchronous contralateral breast cancer, versus those who do not consume alcohol. It is estimated that there is a 5% increase in premenopausal breast cancer per 10 grams of ethanol consumed per day and the risk is even greater at 9%, for postmenopausal breast cancer.

A recent meta-analysis of cohort studies among 209,597 cancer survivors showed an 8% increase in overall mortality and a 17% increased risk for recurrence in the highest versus lowest alcohol consumers and these numbers were statistically significant.

The benefit of alcohol consumption on cardiovascular health likely has been overstated and nondrinkers have lower rates of coronary heart disease and stroke than even light drinkers. Given the increase in the risk of cancer even with low levels of alcohol consumption, the net effect of alcohol is harmful. Alcohol consumption should therefore not be recommended to prevent cardiovascular disease or all-cause mortality.

In conclusion, alcohol is a well-established risk factor for the development of certain cancers and further research is needed to understand the effects of alcohol exposure on the efficacy of chemotherapy, immunotherapy and radiation treatment. Alcohol and Cancer: A Statement of the American Society of Clinical Oncology. LoConte NK, Brewster AM, Kaur JS, et al. DOI: 10.1200/JCO.2017.76.1155 Journal of Clinical Oncology – published online before print November 7, 2017

SUMMARY: The FDA on Sept. 14, 2017 approved MVASI® (Bevacizumab-awwb) as a Biosimilar to AVASTIN® (Bevacizumab). Bevacizumab is a recombinant immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds to Vascular Endothelial Growth Factor (VEGF) and inhibits the interaction of VEGF with its receptors, VEGF receptor-1 and VEGF receptor-2. This in turn inhibits establishment of new blood vessels that are essential for the maintenance and growth of solid tumors. MVASI® is the first Biosimilar approved in the U.S. for the treatment of cancer. A Biosimilar product is a biological product that is approved based on its high similarity to an already approved biological product (also known as reference product). Biological products are made from living organisms including humans, animals and microorganisms such as bacteria or yeast, and are manufactured through biotechnology, derived from natural sources or produced synthetically. Biological products have larger molecules with a complex structure, than conventional drugs (also known as small molecule drugs).

Unlike biological products, conventional drugs are made of pure chemical substances and their structures can be identified. A generic drug is a copy of brand name drug and has the same active ingredient and is the same as brand name drug in dosage form, safety and strength, route of administration, quality, performance characteristics and intended use. Therefore, brand name and the generic drugs are bioequivalent. The Affordable Care Act in 2010 created an abbreviated licensure pathway for biological products that are demonstrated to be “Biosimilar” to, or “interchangeable” with an FDA approved biological product (reference product). The Biosimilar must show that it has no clinically meaningful differences in terms of safety and effectiveness from the reference product. A Biosimilar product can only be approved by the FDA if it has the same mechanism of action, route of administration, dosage form and strength as the reference product, and only for the indications and conditions of use that have been approved for the reference product. Biosimilars are not as easy to manufacture as generics (copies of brand name drugs), because of the complexity of the structure of the biologic product and the process used to make a biologic product. The facilities where Biosimilars are manufactured must also meet the FDA standards.

MVASI® is approved for the treatment of patients with the following cancers:

• Metastatic Colorectal cancer, in combination with intravenous 5-Fluorouracil-based chemotherapy for first or second line treatment. MVASI® is not indicated for the adjuvant treatment of surgically resected Colorectal cancer.

• Metastatic Colorectal cancer, in combination with Fluoropyrimidine-Irinotecan or Fluoropyrmidine-Oxaliplatin-based chemotherapy for the second line treatment of patients who have progressed on a first-line Bevacizumab containing regimen.

• Non-squamous Non Small Cell Lung Cancer, in combination with Carboplatin and Paclitaxel for first line treatment of unresectable, locally advanced, recurrent or metastatic disease.

• Glioblastoma with progressive disease following prior therapy, based on improvement in Objective Response Rate. No data is available demonstrating improvement in disease-related symptoms or survival with Bevacizumab.

• Metastatic Renal cell carcinoma, in combination with Interferon alfa.

• Cervical cancer that is persistent, recurrent, or metastatic disease, in combination with Paclitaxel and Cisplatin or Paclitaxel and Topotecan.

The approval of MVASI® was based on two studies. In the first study, PharmacoKinetics (PK) of biosimilar MVASI® was compared with Bevacizumab, following a single infusion of 3 mg/kg. It was concluded that the PK data was similar between the Biosimilar, MVASI® and Bevacizumab. The second study is a randomized, double-blind, phase III trial, that evaluated the efficacy and safety of MVASI®, compared with Bevacizumab, in patients with non-squamous Non Small Cell Lung Cancer (NSCLC). Patients with non-squamous NSCLC, on first line chemotherapy with Carboplatin and TAXOL® (Paclitaxel), were randomized in a 1:1 ratio to receive either MVASI® (N=328) or Bevacizumab 15 mg/kg (N=314), as an IV infusion, every 3 weeks, for 6 cycles. The Objective Response Rate (ORR) was similar between the two treatment groups (39.0% for MVASI® and 41.7% for Bevacizumab) and these results were not statistically different. The Duration of Response was similar. Adverse events were comparable in the two treatment groups. This study demonstrated that MVASI® was clinically similar to Bevacizumab.

The FDA concluded that the approval of MVASI® was based on comparisons of extensive structural and functional product characterization, animal data, human PharmacoKinetic and pharmacodynamic data, clinical immunogenicity, between MVASI® and AVASTIN® (Bevacizumab), and it was noted that MVASI® is highly similar to AVASTIN® and that there are no clinically meaningful differences between the two products. Randomized, double-blind, phase 3 study evaluating efficacy and safety of ABP 215 compared with bevacizumab in patients with non-squamous NSCLC. Thatcher N, Thomas M, Paz-Ares L, et al. DOI: 10.1200/JCO.2016.34.15_suppl.9095 Journal of Clinical Oncology 34, no. 15_suppl (May 2016) 9095-9095.