References:
1. Swain S, Kim S, Cortes J, et al. Final overall survival (OS) analysis from the CLEOPATRA study of first-line (1L) pertuzumab (Ptz), trastuzumab (T), and docetaxel (D) in patients (pts) with HER2-positive metastatic breast cancer (MBC). European Society for Medical Oncology (ESMO) 2014 Congress. Abstract 350O.
2. Yao JC, Pavel M, Lombard-Bohas C, et al. (EVE) for the treatment of advanced pancreatic neuroendocrine tumors (pNET): Final overall survival (OS) results of a randomized, double-blind, placebo (PBO)-controlled, multicenter Phase III trial (RADIANT-3). European Society for Medical Oncology (ESMO) 2014 Congress. Abstract 1132O.
3. Weber JS, Minor D, D'Angelo S, et al. A phase 3 randomized, open-label study of nivolumab (anti-PD-1; BMS-936558; ONO-4538) versus investigator's choice chemotherapy (ICC) in patients with advanced melanoma after prior anti-CTLA-4 therapy. European Society for Medical Oncology (ESMO) 2014 Congress. Abstract LBA3.
4. Samuel N, Verma S. Cross-comparison of cancer drug approvals among international regulatory bodies. European Society for Medical Oncology (ESMO) 2014 Congress. Abstract 1036O.
5. Antonia S, Goldberg S, Balmanoukian A, et al. A Phase I open-label study to evaluate the safety and tolerability of MEDI4736, an anti-programmed cell death-ligand 1(PD-L1) antibody, in combination with tremelimumab in patients with advanced non-small cell lung cancer (NSCLC). European Society for Medical Oncology (ESMO) 2014 Congress. Abstract 1327P.
6. McArthur G, Ascierto P, Larkin J, et al. Phase 3, double-Blind, placebo-controlled study of vemurafenib versus vemurafenib + cobimetinib in previously untreated BRAFV600 mutation-positive patients with unresectable locally advanced or metastatic melanoma. European Society for Medical Oncology (ESMO) 2014 Congress. Abstract LBA5.
7. Shaw AT, Ou S, Bang Y, et al. Clinical activity of crizotinib in ROS1-rearranged non-small cell lung cancer. European Society for Medical Oncology (ESMO) 2014 Congress. Abstract 1299P.
8. Ryan C, Smith M, Fizazi K, et al. Final overall survival (OS) analysis of COU-AA-302, a randomized phase 3 study of abiraterone acetate (AA) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) without prior chemotherapy. European Society for Medical Oncology (ESMO) 2014 Congress. Abstract 753O.
Slide 1: Pertuzumab Adds Almost 16 Months of Survival in HER2-Positive Breast Cancer:
After a follow-up of 50 months, the final overall survival analysis of the pivotal CLEOPATRA trial, which randomized 808 previously untreated patients, demonstrated a 15.7 month overall survival advantage for HER2-positive metastatic breast cancer patients treated with trastuzumab, chemotherapy, and pertuzumab compared with trastuzumab and chemotherapy alone. Median overall survival was 40.8 months in the control arm compared with 56.5 months in the pertuzumab experimental arm (hazard ratio = 0.68).
Image source: Sandra Swain, MD, Washington Cancer Institute in Washington, DC.
[1]
Slide 2: Improvement in Overall Survival for Advanced Pancreatic Neuroendocrine Cancer:
Everolimus improved overall survival in patients with pancreatic neuroendocrine (pNET) tumors by 6.3 months compared with placebo in the phase III, randomized RADIANT-3 trial. Overall survival was more than 3.5 years (44 months) in the everolimus arm compared with 37.7 in the placebo group, which was not statistically significant (hazard ratio = 0.94;
P
= .03). A high crossover rate of 85% of patients from the placebo to the everolimus arm likely accounted for the relatively long overall survival in the placebo group. Using a model to correct for the large crossover effect, the survival rates with everolimus compared with placebo were 82.6% and 67.7% in the everolimus arm at 12 and 24 months compared with 74.9% and 55.6% in the placebo arm, respectively.
Image source: James C. Yao, University of Texas, MD Anderson Cancer Center, Houston, Texas.
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Slide 3: Longer Duration of Response With Nivolumab in Melanoma:
Metastatic melanoma patients treated with the anti-PD-1 immunotherapy nivolumab had a 32% response rate compared with an 11% rate in patients treated with chemotherapy. The phase III trial, called CheckMate 037, randomized 405 melanoma patients 2:1. All patients had previously been treated with at least one systemic therapy for their advanced disease. Median response time was 3.6 months in the chemotherapy arm and has not yet been reached in the nivolumab arm. Some patients in the nivolumab arm have been responding for 10 months or more and 36 of the 38 responsive patients are continuing to respond. These are the first phase III clinical trial results with nivolumab reported.
Image source: Jeffrey S. Weber, MD, PhD, Moffitt Cancer Center, Tampa, Florida.
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Slide 4: US Approves Cancer Drugs Faster Than Canada or Europe:
Canada and Europe are at times as much as year or more slower to approve new cancer drugs compared to the US Food and Drug Administration, according to a new study. According to the researchers, the results point to a need for better collaboration among clinicians and international health authorities so that, internationally, patients have access to the best treatments. The study compared the approval times of 41 cancer drugs finding that the average time to approval by the FDA was 6 months shorter compared with the timing of Europe’s European Medicines Agency (EMA) (
P
P Image source: Sunil Verma, Sunnybrook Odette Cancer Center, Toronto, Canada.[4]
Slide 5: Early Results of Anti-PD-1/Anti-CTLA-4 Combo for Lung Cancer:
The combination of two immunotherapies, MEDI4736, an anti-PD-1 antibody, and tremelimumab, an anti-CTLA-4 antibody, was shown to be relatively safe and had some activity in a small cohort of 12 patients with advanced non-small-cell lung cancer. Frequently reported adverse events included increased amylase, abdominal pain, arthralgia, colitis, diarrhea, epigastric discomfort, fatigue, and nausea. After 8 weeks, two patients have unconfirmed partial responses and three patients have tumor shrinkage but not enough to meet partial response criteria. Ten patients remain on study.
Image source: Scott Antonia, MD, PhD, medical oncologist, program leader of immunology program at the Moffitt Cancer Center, Tampa, Florida.
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Slide 6: BRAF + MEK Targeted Combo Improves PFS in BRAF-Mutated Melanoma:
The combination of the BRAF inhibitor vemurafenib plus the MEK inhibitor cobimetinib improved progression-free survival and response rates in patients with
BRAF
-mutated metastatic melanoma compared with vemurafenib alone. Vemurafenib is already approved by the US Food and Drug Administration for
BRAF
-mutated metastatic melanoma. Median progression-free survival was 9.9 months with the combination vs 6.2 months in control arm (
P
P Image source: European Society for Medical Oncology, 2014, Madrid, Spain.[6]
Slide 7: ROS1-Rearranged NSCLC Responds to Crizotinib:
Treatment with crizotinib of advanced non-small-cell lung cancer (NSCLC) patients whose tumors harbor a rearrangement in the
ROS1
gene resulted in tumor shrinkage in 36 of 50 patients-a 72% overall response-and tumor growth was suppressed in another 9 patients (18% stable disease). Crizotinib is already approved by the US Food and Drug Administration for NSCLC patients whose tumors harbor an
ALK
rearrangement. The median progression-free survival was 19.2 months.
Image source: Alice Shaw, MD, PhD, of the Massachusetts General Hospital (MGH) Cancer Center.
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Slide 8: Significant Improvement in Overall Survival With Abiraterone for Chemotherapy-Naive Prostate Cancer:
In a randomized trial of 1,088 participants, abiraterone acetate plus prednisone significantly extended overall survival compared with prednisone alone in patients with chemotherapy-naive metastatic castration-resistant prostate cancer. Men in the abiraterone arm had a 19% reduction in risk of death. These are the results of the final analysis of the COU-AA-302 phase III trial after a median follow-up of more than 4 years (49.4 months). Patients receiving the combination had a median overall survival of 34.7 months compared with 30.3 months in the control arm (hazard ratio = 0.80,
P
= .0027).
Image source: European Society for Medical Oncology, 2014, Madrid, Spain.
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