Author: RR

Late Breaking Abstract – ESMO 2018 First Line BAVENCIO® plus INLYTA® Highly Effective in Advanced Renal Cell Carcinoma

RR

SUMMARY: The American Cancer Society estimates that 73,820 new cases of kidney and renal pelvis cancers will be diagnosed in the United States in 2019 and about 14,770 people will die from the disease. Renal Cell Carcinoma (RCC) is by far the most common type of kidney cancer and is about twice as common in men as in women. Modifiable risk factors include smoking, obesity, workplace exposure to certain substances and high blood pressure. The five year survival of patients with advanced RCC is less than 10% and there is significant unmet need for improved therapies for this disease. SUTENT® (Sunitinib) is a MultiKinase Inhibitor (MKI) which simultaneously targets the tumor cell wall, vascular endothelial cell wall as well as the pericyte/fibroblast/vascular/ smooth vessel cell wall and is capable of specifically binding to tyrosine kinases, inhibiting the earlier signaling events and thereby inhibits phosphorylation of VEGF receptor, PDGF receptor, FLT-3 and c-KIT. SUTENT® is the standard first-line intervention for treatment naïve patients with advanced RCC. In a large, multi-center, randomized, phase III study, the median Progression Free Survival (PFS) with SUTENT® was 9.5 months, the Objective Response Rate (ORR) was 25%, and the median Overall Survival was 29.3 months, when compared with Interferon Alfa, in patients with treatment-naïve Renal Cell Carcinoma. This was however associated with a high rate of hematological toxicities.International-Metastatic-RCC-Database-Consortium-(IMDC)

BAVENCIO® (Avelumab) is a human, immunoglobulin G1 lambda, PD-L1 targeted monoclonal antibody that binds to PD-L1 and blocks the interaction between PD-L1 and its receptors PD-1. This in turn negates the inhibitory effects of PD-L1 on the immune response by unleashing the immune system and restoring antitumor immune responses. In addition, BAVENCIO® induces Antibody Dependent Cell-mediated Cytotoxicity (ADCC). INLYTA® (Axitinib) is a kinase inhibitor and inhibits receptor tyrosine kinases including Vascular Endothelial Growth Factor Receptors (VEGFR)-1, VEGFR-2, and VEGFR-3. These receptors have been implicated in pathologic angiogenesis, tumor growth, and cancer progression. INLYTA® is approved by the FDA for the treatment of advanced Renal Cell Carcinoma (RCC) after failure of one prior systemic therapy. The rationale behind combining these two agents was that BAVENCIO® stimulates the immune system while INLYTA® inhibits tumor neoangiogenesis by preventing VEGF activity. Preclinical data suggested that combining these two agents is effective, as their mechanisms of action complement each other. A combination of BAVENCIO® and INLYTA® also showed encouraging antitumor activity among patients with advanced RCC in a phase 1b trial.Unleashing-T-Cell-Function-with-PD-1-and-PD-L1-Antibodies

JAVELIN Renal 101 is a global, randomized phase III trial in which 886 patients with clear cell advanced Renal Cell Carcinoma who had no prior systemic therapy, were randomly assigned in a 1:1 to receive BAVENCIO® 10 mg/kg IV every 2 weeks along with INLYTA® 5 mg orally twice daily, in 6 week cycles (N=442) or SUTENT® 50 mg orally daily, 4 weeks on followed by 2 weeks off (N=444). This study included all MSKCC (Memorial Sloan Kettering Cancer Center) prognostic subgroups (good, intermediate, and poor risk). According to the IMDC (International Metastatic RCC Database Consortium), 21% were in the favorable risk group, 62% were in the Intermediate risk group and 16% were in the poor risk group. Among the enrolled patients, 63.2% (N=560) patients were PD-L1positive (1% or more positive immune cells) of whom 270 patients received the BAVENCIO® and INLYTA® combination whereas 290 patients received SUTENT®. The Primary endpoints were Progression Free Survival (PFS) and Overall Survival (OS) in the PD-L1 positive group and Secondary endpoints included PFS and OS irrespective of PD-L1 expression, Objective Response Rate (ORR) and Safety.

It was noted that in the patient group with PD-L1 positive tumors, the median PFS was 13.8 months in the combination group compared to 7.2 months in the single agent SUTENT® group (HR=0.61; P<0.0001). The median PFS in patients irrespective of PD-L1 expression was 13.8 months with the combination treatment compared to 8.4 months with SUTENT® (HR=0.69; P=0.0001). The confirmed Objective Response Rate (ORR) among those with PD-L1 positive tumors was 55.2% in the combination group and 25.5% in the SUTENT® group. The benefit with combination treatment was noted in all prognostic risk groups. The OS data were immature at the time of data cutoff. Grade 3 or more treatment related adverse events were similar in both treatment groups and led to discontinuation of drug in 22.8% of patients in the combination group versus 13.4% in the SUTENT® group.

It was concluded that a combination of BAVENCIO® given along with INLYTA® significantly improved Progression Free Survival as well as Objective Response Rate, irrespective of PD-L1 expression, and across all prognostic risk groups. The authors added that these results support this combination as a potential new first line standard of care for patients with advanced Renal Cell Carcinoma. JAVELIN Renal 101: a randomized, phase III study of avelumab + axitinib vs sunitinib as first-line treatment of advanced renal cell carcinoma (aRCC). Motzer RJ, Penkov K, Hannen JBAG, et al. Proceedings from the 2018 ESMO Congress; October 19-23, 2018; Munich, Germany. Abstract LBA6_PR.

STIVARGA® Dose Optimization Improves Outcomes in Patients with Metastatic Colorectal Cancer

RR

SUMMARY: ColoRectal Cancer (CRC) is the third most common cancer diagnosed in both men and women in the United States. The American Cancer Society estimates that approximately 140,250 new cases of CRC will be diagnosed in the United States in 2018 and about 50,630 patients are expected to die of the disease. The lifetime risk of developing CRC is about 1 in 21 (4.7%). Even though colon cancer localized to the bowel is potentially curable with surgery and adjuvant chemotherapy, advanced colon cancer is often incurable. STIVARGA® (Regorafenib), is an oral multi-kinase inhibitor and inhibits multiple kinases including VEGF1, VEGF2, VEGF3, PDGFR, FGFR involved in tumor angiogenesis and KIT, RET, RAF-1, BRAF involved in oncogenesis. STIVARGA® is approved by the FDA for the treatment of patients with metastatic CRC, who have progressed on 5FU, ELOXATIN® (Oxaliplatin), CAMPTOSAR® (Irinotecan), anti-VEGF and anti-EGFR therapies, at a dose of 160 mg orally, once daily for the first 21 days of each 28-day cycle. The approval was based on a phase III trial in which patients receiving STIVARGA® had a statistically significant improvement in the Overall Survival (OS) and Progression Free Survival (PFS), compared to placebo.

The starting dose of STIVARGA® has been an obstacle and toxicities such as Palmar-Plantar Erythrodysesthesia Syndrome (PPES) commonly occurring during the first 2 weeks, as well as fatigue and hypertension have limited its use. Various dosing schedules have been implemented into clinical practice, despite the absence of reliable supportive data. There is therefore a need to optimize the dose of STIVARGA® in patients with refractory mCRC to maintain efficacy, while improving the tolerability profile. CORRELATE study looked at the data from the real-world setting of refractory mCRC regarding the dosing of STIVARGA® and safety, whereas the ReDos study evaluated a dose-escalation strategy, starting with a lower dose of STIVARGA®.

CORRELATE is a prospective, international observational study conducted in 13 countries to evaluate the use STIVARGA® in a real-world setting, based on safety and efficacy. The primary objective of this study was to assess safety. This final analysis describes the real-world dosing of STIVARGA® in mCRC.

Of the 1037 patients included in this study, 57% started treatment at 160 mg, 30% at 120 mg, and 13% at 80 mg or less. The mean dose administered was 75% of the approved dose. The median patient age was 65 years and majority of the patients had an ECOG performance status (PS) of 0-1 (87%). Dose reductions were more frequent in the 160 versus 120 mg group and treatment modifications were most commonly due to treatment related adverse events (66%). Most treatment discontinuations (49%) were due to radiologic disease progression, whereas 19% were due to STIVARGA® related adverse events. Treatment related adverse events of any grade occurred in 95% of patients, and 80% were attributed to STIVARGA®. Median overall survival (OS) was 7.6 months and the estimated 1-year OS was 34%.

It was concluded from this real-world, observational study that the starting dose of STIVARGA® for nearly half of patients was less than 160 mg/day and the common treatment related adverse events were generally consistent with the known safety profile of STIVARGA® in mCRC. Despite the dose modifications of STIVARGA®, there was no significant impact on its efficacy in terms of the median OS and median PFS.

ReDOS is a randomized phase II study in which STIVARGA® dose-escalation strategy beginning at a lower starting dose of 80 mg daily and ending at 160 mg daily was compared with the standard dose, in patients with refractory mCRC. In this dose escalation study, patients in Arm A (N=54) received STIVARGA® 80 mg daily, with weekly dose escalation up to 160 mg daily, if no significant drug-related toxicities were experienced, where as in Arm B (N=62), patients received the standard dose of STIVARGA® 160 mg daily, for 21 days of a 28-day cycle. The median age was 61 years and both treatment groups were well balanced. The Primary endpoint was the proportion of patients who completed 2 cycles of treatment and initiated the 3rd cycle if there was no progression.

The study met its primary endpoint with 43% of patients on Arm A initiating the 3rd cycle versus only 25% of patients on Arm B (P=0.028). The median Overall Survival (OS) was improved in Arm A versus Arm B (9 months versus 5.9 months ; P=0.094). The median Progression Free Survival (PFS) was 2.5 months for Arm A and 2 months for Arm B (P=0.55). Overall grade 3 and 4 toxicities were lower on Arm A versus Arm B and multiple Quality Of Life parameters were improved in Arm A versus Arm B, at week 2 of the first cycle.

It was concluded that weekly dose escalation of STIVARGA® from 80 mg to 160 mg daily was superior to a starting dose of 160 mg daily. Based on this study, the NCCN has updated its ColoRectal Cancer (CRC) guidelines, recommending a weekly STIVARGA® dose-escalation strategy beginning at 80 mg and ending at 160 mg, for previously treated patients with metastatic ColoRectal Cancer.

Real-world dosing of regorafenib (REG) in metastatic colorectal cancer (mCRC): final results from the prospective, observational CORRELATE study. O'Connor JM, Ducreux M, Petersen LN, et al. Ann Oncol. 2018;29 (suppl_8): viii150-viii204. 10.1093/annonc/mdy281

Regorafenib dose optimization study (ReDOS): Randomized phase II trial to evaluate dosing strategies for regorafenib in refractory metastatic colorectal cancer (mCRC)-an ACCRU Network study. Bekaii-Saab TS, Ou FS, Anderson DM, et al. J Clin Oncol. 2018;36(suppl 4S; abstr 611)

Late Breaking Abstract – ASH 2018 IMBRUVICA® and RITUXAN® Combination Superior to FCR in Younger Patients with CLL

RR

SUMMARY: The American Cancer Society estimates that for 2018, about 20,940 new cases of Chronic Lymphocytic Leukemia (CLL) will be diagnosed in the US and 4,510 patients will die of the disease. CLL accounts for about 25% of the new cases of leukemia and the average age at the time of diagnosis is around 71 years. B-cell CLL is the most common type of leukemia in adults, accounting for about 11% of all hematologic malignancies. Chemoimmunotherapy with Fludarabine, Cyclophosphamide, and Rituximab (FCR) has long been the gold standard and the most commonly used treatment regimen for younger, fit, treatment naïve patients with chronic lymphocytic leukemia. This is based on phase III trial data showing improvement in both Progression Free Survival (PFS) and Overall Survival (OS) compared with chemotherapy alone. FCR regimen however is associated with significant toxicities and cannot be tolerated by all CLL patients. IMBRUVICA® (Ibrutinib) is an oral, irreversible inhibitor of BTK and inhibits cell proliferation and promotes programmed cell death (Apoptosis) by blocking B-cell activation and signaling. IMBRUVICA® in phase III trials showed improved PFS and OS when compared to Chlorambucil in previously untreated, elderly patients with CLL. Nonetheless, the efficacy of IMBRUVICA® as a first-line treatment for younger CLL patients (70 years or younger), compared to the most efficacious regimen such as FCR, is unknown.BCR-Signal-Pathways

E1912, led by the ECOG-ACRIN Research Group (ECOG-ACRIN), is a randomized phase III study in which IMBRUVICA® (Ibrutinib) plus RITUXAN® (Rituximab) was compared to Fludarabine, Cyclophosphamide, and RITUXAN® (FCR) chemotherapy regimen, in previously untreated patients aged 70 years or younger with Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL). In this trial, 529 patients were randomly assigned in a 2:1 ratio to receive IMBRUVICA® 420 mg orally daily until disease progression along with RITUXAN® 50 mg/m2 on day 1 of cycle 2, 325 mg/m2 on day 2 of cycle 2, 500 mg/m2 on day 1 of cycles 3-7 (N=354) or six courses of Fludarabine 25 mg/m2 IV along with Cyclophosphamide 250 mg/m2 IV days 1-3 and RITUXAN® 50 mg/m2 IV on day 1 of cycle 1, 325 mg/m2 on day 2 of cycle 1, 500 mg/m2 on day 1 of cycles 2-6, given every 28 days (N=175). The median age was 58 years and 40% of the patients were 60 years of age or older. The Primary endpoint was Progression Free Survival (PFS) and the Secondary endpoint was Overall Survival (OS).

With a median follow up of 33.4 months, at the first interim analysis, IMBRUVICA® plus RITUXAN® significantly improved PFS compared to FCR (HR=0.35; P<0.0001), with a 65% reduction in the risk of progression or death with IMBRUVICA® plus RITUXAN® compared with FCR. The combination of IMBRUVICA® plus RITUXAN® also demonstrated improved OS (HR=0.17; P=0.0003) and this suggested that IMBRUVICA® plus RITUXAN® combination reduced the risk of death by 83% compared with FCR. In a subgroup analysis, the PFS benefit with IMBRUVICA® plus RITUXAN® was seen independent of age, sex, Performance Status (0-2), disease stage, as well as presence or absence of cytogenetic abnormality, deletion 11q23. At the time of this analysis, IMBRUVICA® plus RITUXAN® was also superior to FCR among IGHV unmutated patients (HR=0.26; P<0.0001), suggesting a 74% reduction in the risk of progression or death with IMBRUVICA® plus RITUXAN®, compared to FCR. A statistically significant benefit however was not observed among those with IGHV mutations, although there was a positive trend noted (HR=0.44; P=0.07). Treatment-related Grade 3 and 4 toxicities were significantly lower with IMBRUVICA® compared with FCR (58% versus 72%, respectively; P=0.004). FCR was more frequently associated with Grade 3 and 4 neutropenia (44% versus 23%) as well as infectious complications (18% versus 7%).

It was concluded that a combination of IMBRUVICA® and RITUXAN®, significantly improved PFS and OS, when compared to FCR, with fewer toxicities, among patients 70 years of age or under, with previously untreated CLL. The authors noted that these findings have immediate practice changing implications and establish IMBRUVICA® – based therapy as the most effective first-line therapy for untreated patients with CLL. Randomized Phase III Study of Ibrutinib (PCI-32765)-Based Therapy Vs. Standard Fludarabine, Cyclophosphamide, and Rituximab (FCR) Chemoimmunotherapy in Untreated Younger Patients with Chronic Lymphocytic Leukemia (CLL): A Trial of the ECOG-ACRIN Cancer Research Group (E1912. Shanafelt TD, Wang V, Kay NE, et al. Presented at the 2018 ASH Annual Meeting. December 1-4, 2018; San Diego. Abstract LBA-4.

Baseline Corticosteroid Use at Start of PD-1/PD-L1 Inhibitor Therapy Negatively Affects Outcomes in NSCLC

RR

SUMMARY: Lung cancer is the second most common cancer in both men and women and accounts for about 14% of all new cancers and 27% of all cancer deaths. The American Cancer Society estimates that for 2018 about 234,030 new cases of lung cancer will be diagnosed and over 154,050 patients will die of the disease. Lung cancer is the leading cause of cancer-related mortality in the United States. Non Small Cell Lung Cancer (NSCLC) accounts for approximately 85% of all lung cancers. Immunotherapy with PD-1 (Programmed cell Death 1) and PD-L1 (Programmed cell Death Ligand 1) inhibitors have demonstrated a clear survival benefit both as a single agent or in combination, compared with standard chemotherapy, in both treatment-naive and previously treated patients for advanced Non Small Cell Lung Cancer (NSCLC). It is now standard therapy for patients with lung cancer. Immuno-Oncology therapies unleash the T cells by blocking the Immune checkpoint proteins, thereby resulting in T cell proliferation, activation and a therapeutic response.

Patients with NSCLC often are treated with corticosteroids for a variety of reasons including fatigue, dyspnea, decreased appetite, and symptomatic brain metastases. Corticosteroids by virtue of their immunosuppressive properties can potentially effect on T-cell function and for this reason, use of these agents before the start of therapy with PD-(L)1 blockade has been a uniform exclusion criterion in clinical trials of Immune Checkpoint Blockade therapies. It is however becoming increasing clear that corticosteroids use for the management of immune-related adverse events do not seem to negatively impact outcomes. Nonetheless, there are presently no data regarding the impact of corticosteroid use at baseline, on the efficacy of Immune Checkpoint Inhibitors. In this publication, the authors evaluated the potential impact of systemic corticosteroids at the start of Immune Checkpoint Blockade, on the efficacy of PD-(L)1 inhibitors.

The authors in this study identified patients with advanced NSCLC who were treated with single-agent PD-(L)1 inhibitor (Pembrolizumab, Nivolumab, Atezolizumab, or Durvalumab) from two institutions – Memorial Sloan Kettering Cancer Center (N=455) and Gustave Roussy Cancer Center (N=185), between April 2011 to September 2017. Clinical and pharmacy records were reviewed to identify corticosteroid use at the time of beginning anti-PD-(L)1 therapy. Information on the use of corticosteroids within 30 days of the start of PD-(L)1 blockade, type of corticosteroid used, indication and route of administration were collected for the MSKCC cohort. Patient characteristics, including age, gender, histology, ECOG Performance Status, and smoking history were collected for all patients. Efficacy outcomes following treatment with PD-(L)1 inhibitors blockade was determined by local radiologists and all patients were followed up until death or data lock.

It was noted that 14% (N=90) of the 640 patients treated with single-agent PD-(L)1 inhibitor received 10 mg or more of prednisone daily at the start of the treatment with a PD-(L)1 inhibitor. The most common indications for treatment with corticosteroids were dyspnea or other respiratory symptoms (33%), fatigue (21%), and brain metastases (19%). Patient characteristics were well balanced between those who did or did not receive corticosteroids, with two exceptions – patients with poor performance status and history of brain metastases were more common in those who received corticosteroids.

In the pooled cohort of patients from both participating institutions, patients receiving baseline corticosteroids compared with patients not receiving corticosteroids experienced a lower Objective Response Rate (7% versus 18%) and worse Progression Free Survival and Overall Survival (P<0.001). The authors performed a multivariable analysis in the pooled cohort (N = 640), incorporating smoking history, performance status, history of brain metastases, and corticosteroid use (Prednisone 10 mg or more versus less than 10 mg), at the start of PD-(L)1 blockade. Prednisone use 10 mg or more was associated with worse Progression Free Survival (P=0.03) and Overall Survival (P<0.001). In the Memorial Sloan Kettering Center cohort of patients, (data unavailable for the Gustave Roussy Cancer Center cohort), patients who discontinued corticosteroids 1-30 days before starting PD-(L)1 blockade had intermediate Progression Free Survival and Overall Survival compared to those who received corticosteroids on the day of PD-(L)1 blockade initiation and those who received no corticosteroids within 30 days of the start of therapy.

The authors concluded that among patients with Non Small Cell Lung Cancer treated with PD-(L)1 blockade, baseline corticosteroid use of 10 mg or more of prednisone equivalent was associated with inferior outcomes. Clinicians should exercise caution and minimize the use, duration, and dose of corticosteroids if immunotherapy with PD-(L)1 blockade is a future consideration. Impact of Baseline Steroids on Efficacy of Programmed Cell Death-1 and Programmed Death-Ligand 1 Blockade in Patients With Non-Small-Cell Lung Cancer. Arbour KC, Mezquita L, Long N, et al. J Clin Oncol. 2018;36:2872-2878

Radiotherapy plus ERBITUX® Inferior to Radiotherapy plus Cisplatin in HPV-Positive Oropharyngeal Squamous Cell Carcinoma

RR

SUMMARY: The Centers for Disease Control and Prevention estimates that in the US, there are more than 16,000 cases of Human PapillomaVirus (HPV)-positive OroPharyngeal Squamous Cell Carcinoma (OPSCC) per year and there has been a significant increase in incidence during the past several decades, due to changes in sexual practices. They represent approximately 70% of all OPSCC in the United States and Canada. HPV-positive oropharyngeal squamous cell carcinoma is an entirely distinct disease entity from HPV-negative oropharyngeal squamous cell carcinoma. Patients with HPV-positive OPSCC tend to be younger males, who are former smokers or nonsmokers, with risk factors for exposure to High Risk HPV (HR-HPV). The HPV-positive primary Squamous Cell Carcinoma tend to be smaller in size, with early nodal metastases, and these patients have a better prognosis compared with patients with HPV-negative Head and Neck Squamous Cell Carcinoma (HNSCC), when treated similarly. Expression of tumor suppressor protein, known as p16, is highly correlated with infection with HPV in HNSCC. Accurate HPV assessment in head and neck cancers is becoming important as it significantly impacts clinical management. HPV status is considered the most important prognostic indicator in patients with head and neck cancer and p16 status is now included in the American Joint Committee on Cancer (AJCC) Staging System.Parts-of-the-Oropharynx

HPV-positive Oropharyngeal Squamous Cell Carcinoma is more sensitive to chemotherapy and radiotherapy than is HPV-negative Oropharyngeal Squamous Cell Carcinoma, which translates to a much better prognosis and survival, when treated with a combination of Cisplatin chemotherapy and radiotherapy. This treatment however can be associated with substantial morbidity and lifelong toxicities such as dry mouth, difficulty swallowing, and loss of taste. Patients deemed unable to tolerate Cisplatin chemotherapy such as the elderly, and those with poor kidney function, receive ERBITUX® (Cetuximab), an Epidermal Growth Factor Receptor (EGFR) inhibitor with radiotherapy.

ERBITUX® is an EGFR targeted monoclonal antibody and the goal of this present study was to find an alternative to Cisplatin, and this study was designed to see if ERBITUX® with radiation would be less toxic than Cisplatin with radiation, without compromising survival among HPV-positive OPSCC patient population. RTOG 1016 is a randomized, multicentre, non-inferiority, phase III trial which included patients with Human PapillomaVirus (HPV)-positive Oropharyngeal Squamous Cell Carcinoma. This study enrolled 987 patients (N=987) at 182 centers in the US and Canada and enrollees had histologically confirmed HPV-positive Oropharyngeal carcinoma and clinical categories included T1-T2, N2a-N3 M0 or T3-T4, N0-N3 M0 groups. Patients were randomly assigned in a 1:1 ratio to receive either radiotherapy plus ERBITUX®, or radiotherapy plus Cisplatin. Treatment groups were well balanced and were stratified by T (T1–T2 vs T3–T4), N category (N0-N2a vs N2b-N3), and smoking history (10 pack-years or less vs more than 10 pack-years). Patients were randomized to receive either ERBITUX® at a loading dose of 400 mg/m2 IV 5-7 days before radiotherapy initiation, followed by ERBITUX® 250 mg/m2 IV weekly for seven doses (N=425) or Cisplatin 100 mg/m 2 on days 1 and 22 of radiotherapy (N=424). All patients received accelerated Intensity-Modulated RadioTherapy (IMRT) delivered at 70 Gy in 35 fractions over 6 weeks at six fractions per week (with two fractions given on one day, at least 6 hours apart). The Primary endpoint was Overall Survival.

The third and final interim analysis was done after a median follow-up of 4.5 years. Radiotherapy plus ERBITUX® did not meet the non-inferiority criteria for Overall Survival and the estimated 5-year Overall Survival was 77.9% in the ERBITUX® group versus 84.6% in the Cisplatin group, suggesting that the Overall Survival on the ERBITUX® arm was significantly inferior to the Cisplatin arm. Progression Free Survival (PFS) was also significantly lower in the ERBITUX® group compared with the Cisplatin group, with a 5-year PFS of 67.3% versus 78.4%, respectively. Five year locoregional failure rates were significantly higher in the ERBITUX® group compared with the Cisplatin group (17.3% versus 9.9%, respectively. Serious (grade 3-5) adverse events were similar for patients in both treatment groups and as expected, toxicities were different, with adverse events of renal toxicity, hearing loss, and bone marrow suppression more common in patients in the Cisplatin group, where as body rash was more common in the ERBITUX® group. All patients in this study were able to complete therapy at the time of this analysis.

It was concluded that this trial is the first randomized clinical trial specifically designed for patients with HPV-positive Oropharyngeal cancer, and among this patient group, radiotherapy plus ERBITUX® showed inferior Overall Survival and Progression Free Survival compared with radiotherapy plus Cisplatin. Radiotherapy plus Cisplatin should therefore be the standard of care for eligible patients with HPV-positive Oropharyngeal carcinoma. Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. Gillison ML, Trotti AM, Harris J, et al. Published:November 15, 2018. DOI:https://doi.org/10.1016/S0140-6736(18)32779-X

ELZONRIS® (Tagraxofusp-erzs)

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The FDA on December 21, 2018 approved ELZONRIS®, a CD123-directed cytotoxin, for Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) in adults and in pediatric patients 2 years and older. ELZONRIS® is a product of Stemline Therapeutics.

ASPARLAS® (Calaspargase pegol-mknl)

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The FDA on December 20, 2018 approved ASPARLAS®, an asparagine specific enzyme, as a component of a multi-agent chemotherapeutic regimen for Acute Lymphoblastic Leukemia (ALL) in pediatric and young adult patients age 1 month to 21 years. This new product provides for a longer interval between doses compared to other available pegaspargase products. ASPARLAS® is a product of Servier Pharmaceuticals LLC.

LYNPARZA® (Olaparib)

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The FDA on December 19, 2018 approved LYNPARZA® for the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube or primary peritoneal cancer, who are in Complete or Partial Response to first-line platinum-based chemotherapy. LYNPARZA® is a product of AstraZeneca Pharmaceuticals LP.