A randomized, double-blind, phase III, non-inferiority clinical trial comparing the efficacy and safety of TA4415V (a proposed Trastuzumab biosimilar) and Herceptin (Trastuzumab reference product) in HER2-positive early-stage breast Cancer patients.

BACKGROUND: This study compared efficacy and safety of TA4415V, a trastuzumab biosimilar, with reference trastuzumab in patients with human epidermal growth factor receptor 2-positive (HER2-positive) early-stage breast cancer treated in the neoadjuvant setting in Iran. METHODS: Patients were randomly assigned to receive neoadjuvant TA4415V or reference trastuzumab concurrently with docetaxel (TH phase) for 4 cycles after treatment with 4 cycles of doxorubicin and cyclophosphamide (AC phase). Chemotherapy was followed by surgery. The primary endpoint was the comparison of pathologic complete response (pCR) rate in the per-protocol population. Secondary endpoints included comparisons of overall response rate (ORR), breast-conserving surgery (BCS), safety, and immunogenicity. RESULTS: Ninety-two participants were analyzed in the per-protocol population (TA4415V, n = 48; reference trastuzumab, n = 44). The pCR rates were 37.50% and 34.09% with TA4415V and reference drug, respectively. The 95% CI of the estimated treatment outcome difference (- 0·03 [95% CI - 0.23 to 0.16]) was within the non-inferiority margin. No statistically significant difference was observed between the groups for other efficacy variables in the ITT population: ORR (89.13% vs. 83.33%; p = 0.72) and BCS (20.37% vs. 12.96%; p = 0.42) in the TA4415V and reference drug group, respectively. At least one grade 3 or 4 adverse events occurred in 27 (50%) patients in the TA4415V group versus 29 (53.70%) in the reference trastuzumab group (p = 0.70). The decrease in left ventricular ejection fraction (LVEF), as an adverse event of special interest (AESI) for trastuzumab, was compared between treatment groups in TH phase. Results demonstrated an LVEF decrease in 7 (12.96%) and 9 (16.67%) patients in TA4415V and reference trastuzumab groups, respectively (p = 0.59). Anti-drug antibodies (ADA) were not detected in any samples of groups. CONCLUSIONS: Non-inferiority for efficacy was demonstrated between TA4415V and Herceptin based on the ratio of pCR rates in HER2-positive early breast cancer patients. In addition, ORR and BCS, as secondary endpoints, were not significantly different. Safety profile and immunogenicity were also comparable between the two groups.

Efficacy and Safety of Proposed Bevacizumab Biosimilar BE1040V in Patients With Metastatic Colorectal Cancer: A Phase III, Randomized, Double-blind, Noninferiority Clinical Trial.

PURPOSE: The purpose of this study was to compare the efficacy and safety of a proposed bevacizumab biosimilar to those of the reference product in patients with metastatic colorectal cancer (mCRC). METHODS: This Phase III, multicenter, randomized, double-blind (patient- and assessor-blind), active-controlled, 2-armed, parallel-group, noninferiority trial was conducted in patients with histologically verified colorectal cancer with evidence of at least 1 metastasis. Patients with mCRC were randomized 2:1 to receive 5 mg/kg IV of either study drug plus FOLFIRI-3 (with repeated irinotecan 100 mg/m2 60-min infusion on day 3) or the reference drug plus FOLFIRI-3 every 2 weeks for 1 year. Progression-free survival (PFS) was the primary end point, and overall survival, objective response rate, and time to treatment failure as well as safety and immunogenicity were secondary end points. The population assessable for PFS was per protocol, and the intention-to-treat population was used for sensitivity analysis. Safety was assessed based on reports of adverse events, laboratory test results, and vital sign measurements. FINDINGS: A total of 126 patients were enrolled; PFS values in the biosimilar and reference arms were 232 days (7.7 months) and 210 days (7 months), respectively (P = 0.47). The hazard ratio of the biosimilar arm versus the reference arm was 0.79 in the per-protocol population (90% CI, 0.46-1.35; P = 0.47). The upper limit for the 2-sided 90% CI was lower than the margin of 1.44, indicating that the biosimilar drug was noninferior to the reference drug. The hazard ratio for overall survival in the intent-to-treat population was 0.99 (95% CI, 0.55-1.80; P = 0.99). The difference between other efficacy end points among the groups was not statistically significant. No significant difference was observed in the comparison of the two arms for safety. The antidrug antibody was positive in 1 patient in each arm. IMPLICATIONS: The proposed biosimilar BE1040V was noninferior to the reference product in terms of efficacy in the treatment of mCRC, and tolerability was comparable between the 2 drugs. ClinicalTrials.gov identifier: NCT03288987.

Concurrent Chemoradiation with Weekly Paclitaxel and Cisplatin for Locally Advanced Cervical Cancer.

Cervical cancer is one of the most common gynecological cancers in Iranian women. This study was initiated to assess whether the combination of paclitaxel and cisplatin with radiation might feasible for these patients. The aim was to assess tumor response and toxicity of weekly cisplatin and paclitaxel along with radiotherapy in the treatment of cervical cancer. Women with primary untreated squamous cell carcinoma of the cervix with FIGO stages IB2 to IIIB were treated with weekly injections of cisplatin 30 mg/m2 and paclitaxel 35 mg/m2 for 5-6 weeks along with radiotherapy. A total of 25 patients were enrolled in this study who completed the intended treatment. Disease was assessed prior to treatment by pelvic examination and contrast enhanced MRI of the abdomen and pelvis. Response was assessed 1 month after completion of treatment by physical examination and 3 months after also by MRI.Toxicity was assessed and was graded using RTOG grading. There was a complete response rate of 84% after 3 months. The major toxicity was grade 1 and 2 anemia (92%). The mean duration of treatment was 58 days. In conclusion, combination chemotherapy with cisplatin and paclitaxel along with radiotherapy in patients with locally advanced squamous cell carcinoma of cervixwas well tolerated, in contrast to other studies, but it seems that there was no increase in tumor response and progression free survival with this treatment regimen.

Breast Necrosis after Chemotherapy for Recurrent Ovarian Cancer: Report of a Case and Review of the Literature.

Breast necrosis is a rare event due to abundant blood supply of the breast. We present an unusual case of partial breast necrosis after chemotherapy for recurrent ovarian cancer. Necrotic tissue sloughed with conservative management and the wound was repaired surgically. We believe that this is the first case report of breast necrosis as a systemic complication of chemotherapy.

Gastrointestinal tumor board: an evolving experience in Tehran Cancer Institute.

Gastrointestinal (GI) cancers are a significant source of morbidity and mortality in Iran, with stomach adenocarcinoma as the most common cancer in men and the second common cancer in women. Also, some parts of Northern Iran have one of the highest incidences of esophageal cancer in the world. Multi-disciplinary organ-based joint clinics and tumor boards are a well-recognized necessity for modern treatment of cancer and are routinely utilized in developed countries, especially in major academic centres. But this concept is relatively new in developing countries, where cancer treatment centres are burdened by huge loads of patients and have to cope with a suboptimum availability of resources and facilities. Cancer Institute of Tehran University of Medical Sciences is the oldest and the only comprehensive cancer treatment centre in Iran, with a long tradition of a general tumor board for all cancers. But with the requirements of modern oncology, there has been a very welcome attention to sub-specialized organ-based tumor boards and joint clinics here in the past few years. Considering this, we started a multi-disciplinary tumor board for GI cancers in our institute in early 2010 as the first such endeavor here. We hereby review this 2-year evolving experience. The process of establishment of a GI tumor board, participations from different oncology disciplines and related specialties, the cancers presented and discussed in the 2 years of this tumor board, the general intents of treatment for the decisions made and the development of interest in this tumor board among the Tehran oncology community will be reviewed. The GI tumor board of Tehran Cancer Institute started its work in January 2010, with routine weekly sessions. A core group of 2 physicians from each surgical, radiation and medical oncology departments plus one gastroenterologist, GI pathologist and radiologist was formed, but participation from all interested physicians was encouraged. An electronic database was kept from the beginning. The number of patients presented in the tumor board increased from 4 in January 2010 to 16 in December 2011. Most patients were presented by radiation oncology department (38%) and then surgical (36%) and medical oncology (20%) departments. Physicians' participation also grew from an average of 8 each session to 12 in the same months, with a number of cancer specialists taking part from other university hospitals in Tehran. A total number of 225 patients were presented with a treatment decision made in this 2-year period. The majority of cases were colorectal (32%), stomach (23%), and esophageal (17%) cancers. The number of pancreatic (7%) and hepatobiliary (6%) cancers were much smaller. Most decisions were for a primary treatment (surgery or radiochemotherapy) and then a neoadjuvant approach.  Tehran Cancer Institute's GI tumor board is one of the first multi-disciplinary organ-based tumor boards in Iran, and as such has made a successful start, establishing itself as a recognized body for clinical decisions and consultations in GI oncology. This experience is growing and evolving, with newer presentation and discussion formats and adapted guidelines for treatment of GI cancers in Iran sought.