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    Posted: 20 Sep 2009 at 11:50am
Dear all,

DW has decided to participate in clinical trial ECOG 5103 (AC-->T +/- B). We will be meeting the oncologist tomorrow for the second time. We are hopeful that the MUGA, Bloodwork, Port Placement, Chemo Schedule etc. will all be ironed out tomorrow and Chemo will start in a week or so.

Regards, Unkle
Wife Dx: Jul/09. Age: 37. Grade: High. Size: 3cm. BRCA: -ve. Lumpectomy: Aug/09. Micromet 1/9 node. Chemo Start: Sep/09. Kicked off E5103 (Taxol reaction). Now dd ACB->dd Abraxane. Zometa (S0307).
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Post Options Post Options   Thanks (0) Thanks(0)   Quote mainsailset Quote  Post ReplyReply Direct Link To This Post Posted: 20 Sep 2009 at 11:53am

question, what is the -B that you refer to?

dx 7/08 TN 14x6.5x5.5 cm tumor

3 Lymph nodes involved, Taxol/Sunitab+AC, 5/09 dbl masectomy, path 2mm tumor removed, lymphs all clear, RAD 32 finished 9/11/09. 9/28 CT clear 10/18/10 CT clear
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Post Options Post Options   Thanks (0) Thanks(0)   Quote dmwolf Quote  Post ReplyReply Direct Link To This Post Posted: 20 Sep 2009 at 12:13pm
Congrats on deciding, and best of luck to both of you.
Love,
Denise W
DX 2/08@43 stg II IDC; gr2,0 nodes. Neoadj chemo, first ACx2 (fail) then CarboTaxotereX6(better). Lump, Rads done 11/08; Clodronate. False alarm queen: PetCT lung & TM marker. NED. PBM w/recon 9/10.
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Post Options Post Options   Thanks (0) Thanks(0)   Quote unklez Quote  Post ReplyReply Direct Link To This Post Posted: 20 Sep 2009 at 2:02pm
Originally posted by mainsailset mainsailset wrote:

question, what is the -B that you refer to?



+/- B means with or without Bevacuzimab. That is the chemical name for Avastin. Three different medical oncologists unrelated to each other and who specialize in breast cancer, including 1 from MSKCC who is not able to offer the trial at this time, recommended this trial to DW.

We know there are some reports that taking Avastin by itself in metastatic breast cancer does not improve overall survival. If we get the arm in which Avastin is given for 10 doses by itself (there is a 40% chance of that) after the end of standard chemo, we can decide to opt out at that time.

Wife Dx: Jul/09. Age: 37. Grade: High. Size: 3cm. BRCA: -ve. Lumpectomy: Aug/09. Micromet 1/9 node. Chemo Start: Sep/09. Kicked off E5103 (Taxol reaction). Now dd ACB->dd Abraxane. Zometa (S0307).
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Post Options Post Options   Thanks (0) Thanks(0)   Quote mainsailset Quote  Post ReplyReply Direct Link To This Post Posted: 20 Sep 2009 at 2:12pm
So she'll be taking AC then Taxol with or without an Avastin booster? And what is MSKCC?
Interesting the order they're giving this.
dx 7/08 TN 14x6.5x5.5 cm tumor

3 Lymph nodes involved, Taxol/Sunitab+AC, 5/09 dbl masectomy, path 2mm tumor removed, lymphs all clear, RAD 32 finished 9/11/09. 9/28 CT clear 10/18/10 CT clear
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Post Options Post Options   Thanks (0) Thanks(0)   Quote unklez Quote  Post ReplyReply Direct Link To This Post Posted: 20 Sep 2009 at 2:20pm
The order in which the drugs will be given is as follows:

4 Biweekly cycles of AC with B (Avastin) or Placebo
followed by
12 Weekly T with 4 Triweekly B (Avastin) or Placebo
followed by unblinding
followed by
B (Avastin) if patient is in that arm

MSKCC is Memorial Sloan Kettering Cancer Center

Wife Dx: Jul/09. Age: 37. Grade: High. Size: 3cm. BRCA: -ve. Lumpectomy: Aug/09. Micromet 1/9 node. Chemo Start: Sep/09. Kicked off E5103 (Taxol reaction). Now dd ACB->dd Abraxane. Zometa (S0307).
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Post Options Post Options   Thanks (0) Thanks(0)   Quote mainsailset Quote  Post ReplyReply Direct Link To This Post Posted: 20 Sep 2009 at 2:53pm
Interesting, I wonder why the Taxol in 2nd place.
dx 7/08 TN 14x6.5x5.5 cm tumor

3 Lymph nodes involved, Taxol/Sunitab+AC, 5/09 dbl masectomy, path 2mm tumor removed, lymphs all clear, RAD 32 finished 9/11/09. 9/28 CT clear 10/18/10 CT clear
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Post Options Post Options   Thanks (0) Thanks(0)   Quote mainsailset Quote  Post ReplyReply Direct Link To This Post Posted: 20 Sep 2009 at 2:57pm
Did you by any chance see this discussion from back in '08?
dx 7/08 TN 14x6.5x5.5 cm tumor

3 Lymph nodes involved, Taxol/Sunitab+AC, 5/09 dbl masectomy, path 2mm tumor removed, lymphs all clear, RAD 32 finished 9/11/09. 9/28 CT clear 10/18/10 CT clear
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Post Options Post Options   Thanks (0) Thanks(0)   Quote unklez Quote  Post ReplyReply Direct Link To This Post Posted: 20 Sep 2009 at 3:20pm
Originally posted by mainsailset mainsailset wrote:

Did you by any chance see this discussion from back in '08?


I had not seen it before. But is there anything in that discussion that you want us to know about?

Wife Dx: Jul/09. Age: 37. Grade: High. Size: 3cm. BRCA: -ve. Lumpectomy: Aug/09. Micromet 1/9 node. Chemo Start: Sep/09. Kicked off E5103 (Taxol reaction). Now dd ACB->dd Abraxane. Zometa (S0307).
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Post Options Post Options   Thanks (0) Thanks(0)   Quote unklez Quote  Post ReplyReply Direct Link To This Post Posted: 20 Sep 2009 at 3:21pm
Originally posted by mainsailset mainsailset wrote:

Interesting, I wonder why the Taxol in 2nd place.


Not sure I understand the question. Can you please explain?

Wife Dx: Jul/09. Age: 37. Grade: High. Size: 3cm. BRCA: -ve. Lumpectomy: Aug/09. Micromet 1/9 node. Chemo Start: Sep/09. Kicked off E5103 (Taxol reaction). Now dd ACB->dd Abraxane. Zometa (S0307).
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Post Options Post Options   Thanks (0) Thanks(0)   Quote mainsailset Quote  Post ReplyReply Direct Link To This Post Posted: 21 Sep 2009 at 5:32am
I was wondering if you had pm'd any of the people already on the trial to see how they had fared. I know from my trial that the BP issue can be very real and wasn't sure if you had already been aware of that side effect.
On my trial the Taxol came first together with the Sutent, then followed by AC. Different order. Wondering why your trial will have a different and what the thought process was. With mine they were trying to cut off the source of 'nutrition' to the tumor as quickly as possible, reduce the size then follow with the killer hammer of AC.
 
I also saw that the poster had 2nd posted over in the Recurrence thread but didn't check that one out. Could be interesting. I know that one of the members who was posting has since passed away, I miss her in particular as she always had such insight.
dx 7/08 TN 14x6.5x5.5 cm tumor

3 Lymph nodes involved, Taxol/Sunitab+AC, 5/09 dbl masectomy, path 2mm tumor removed, lymphs all clear, RAD 32 finished 9/11/09. 9/28 CT clear 10/18/10 CT clear
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Post Options Post Options   Thanks (0) Thanks(0)   Quote cg--- Quote  Post ReplyReply Direct Link To This Post Posted: 21 Sep 2009 at 4:22pm

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FROM THE LITERATURE

Bevacizumab Plus Erlotinib: Another Targeted Treatment Option for Hepatocellular Carcinoma?

Hepatocellular carcinoma (HCC) is one of the most common and devastating malignant diseases worldwide, with a median overall survival (OS) of much less than one year in patients with advanced disease. A majority of patients with advanced HCC are not amenable to curative surgery or liver-directed therapy and are typically refractory to chemotherapy. The oral multikinase inhibitor of the vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor β and Raf, sorafenib (Nexavar®), has demonstrated survival advantages in advanced HCC in 2 multicenter phase III clinical trials (Llovet et al. N Engl J Med. 2008; Cheng et al. Lancet Oncology. 2009) and has recently become the standard of care for this patient population. These promising findings have paved the way for the investigation of other targeted agents and their combinations that may improve the prognosis of patients with advanced HCC. In a considerable number of patients, these highly vascular tumors not only showed an increased expression of vascular endothelial growth factor (VEGF) and VEGFR but also a membranous epidermal growth factor receptor (EGFR) overexpression, which was the rationale for the study of bevacizumab and erlotinib described herein.

A phase II single-arm, safety/efficacy trial of bevacizumab (Avastin®; 10 mg/kg q14d) and erlotinib (Tarceva®; 150 mg PO daily) given continuously for 28-day cycles was conducted in patients with advanced HCC refractory to surgical or regional therapies. A total of 40 patients were treated and evaluated for efficacy/safety. Combination therapy resulted in a 16-week progression-free survival (PFS) of 62.5% (primary endpoint). Results of the secondary efficacy outcomes included a confirmed response rate of 25%, median PFS of 9.0 months, and median OS of 15.7 months. The combination of bevacizumab plus erlotinib seems safe and manageable in patients with advanced HCC. Adverse events were consistent with the known safety profiles of bevacizumab and erlotinib.

Overall, patients with advanced HCC derived significant clinical benefit from treatment with bevacizumab plus erlotinib. This study is the first to report a clinically meaningful advantage in this patient population using a combination of growth factor signaling modifiers. As a result, bevacizumab combined with erlotinib warrants comparison with the current standard of care in randomized controlled trials of patients with advanced-stage HCC.

Thomas MB, et al. J Clin Oncol. 2009 Jan 12. [Epub ahead of print]

Single-Agent Bevacizumab Shows Significant Clinical Activity in Recurrent Glioblastoma

Glioblastoma is one of the most aggressive primary brain tumors, with an unfavorable prognosis mainly due to its high propensity for tumor recurrence. Typically, patients with recurrent glioblastoma have a median survival of 3 to 6 months, with very few treatment options beyond radiation therapy and chemotherapy; therefore, it is an area of continuous medical need for improved treatment strategies. Bevacizumab is a humanized monoclonal antibody directed against the VEGF, a pro-angiogenic cytokine. Bevacizumab binds to VEGF and inhibits VEGFR binding, thereby preventing the growth of tumor blood vessels. Gliomas are highly vascular tumors and it was shown in preclinical models that VEGF is expressed abundantly in glioblastoma. Previously, bevacizumab combined with irinotecan has shown significant antitumor activity in this patient population; however, irinotecan’s contribution to this combination was questioned (Chamberlain. J Clin Oncol. 2008). In 2 large multicentric trials of single-agent irinotecan reported radiographic response rates were low with no prolongation of PFS benefit. As a result, the phase II study reviewed herein was conducted to assess single-agent bevacizumab (10 mg/kg every 2 weeks) in recurrent glioblastoma. In this study, patients who progressed while on bevacizumab were immediately also given irinotecan (340 mg/m2 or 125 mg/m2 every 2 weeks depending on use of enzyme-inducing antiepileptic drugs). The primary endpoint was PFS at 6 months (PFS6), and the secondary endpoint was radiographic response rate.

A total of 48 patients were treated and evaluated for efficacy/safety. Single-agent bevacizumab resulted in a PFS6 of 29%, radiographic response rate of 71% and 35% by Levin and MacDonald criteria, respectively, median PFS of 16 weeks, 6-month OS of 57%, and median OS of 31 weeks. Furthermore, treatment with single-agent bevacizumab demonstrated clinical benefit as evidenced by decreased cerebral edema in 50% of patients and reduced corticosteroid use (59% average decrease in dose) in 58% of patients who were receiving corticosteroids at the start of treatment. No objective responses were observed in any of the patients (n = 19) treated with bevacizumab plus irinotecan at progression. The most common drug-related toxicities reported in this study included thromboembolic events (12.5%), hypertension (12.5%) that was well controlled with antihypertensive medication, hypophosphatemia (6%), and thrombocytopenia (6%).

Overall, bevacizumab monotherapy was well tolerated and provided significant clinical benefit in heavily-pretreated patients with recurrent glioblastoma. The authors noted that although bevacizumab seems to have contributed most of the activity in treating this patient population, the contribution by irinotecan if both agents are used together as initial therapy cannot be excluded. Therefore, a randomized phase III trial is warranted to determine if irinotecan adds any benefit to treatment with bevacizumab.

Freisl TN, et al. J Clin Oncol. 2008 Dec 29. [Epub ahead of print]


Controversies and Challenges of Adjuvant Dosing of Trastuzumab

Trastuzumab (Herceptin®), a humanized monoclonal HER2/neu-targeted antibody, has demonstrated a significant reduction in recurrence rate (39% to 52%) and mortality (30%) in patients with aggressive HER2-positive breast cancer in 5 adjuvant clinical trials (HERA, NSABP-B31, NCCTG-N9831, BCIRG006, and FinHer). However, controversies relating to the use of trastuzumab (such as optimal timing and duration; its use with taxanes and radiotherapy; its role in small node-negative tumors; and cost-effectiveness) have emerged worldwide due to the practice-changing results of these trials and have been discussed in a recent evidence-based review.

The following are key findings from the review:

  • The optimum timing of trastuzumab initiation is still unknown because of large variations in the 5 trials. However, delayed therapy (HERA approach) does not appear to compromise efficacy and combined therapy (with taxanes with or without radiotherapy) seems to be no more toxic. The authors also emphasized that trastuzumab should not be administered concurrently with anthracyclines outside of the clinical trial setting due to an increased risk of cardiotoxicity.
  • No conclusion could be drawn from the 5 trials as far as the optimum duration of therapy. Although there is evidence from the FinHer trial for a shorter duration of treatment, which is economically attractive and could potentially be less toxic, 12 months of trastuzumab therapy will continue to be the empirical standard.
  • The controversy over how to sequence or combine trastuzumab with taxanes remains unclear. Results from the NCCTG-N9831 trial show that concurrent administration with taxanes may be more efficacious, but also more cardiotoxic. Until the results from the NCCTG-N9831 study are updated, the scheduling of taxanes and trastuzumab will be determined based on the preference and experience of the physician.
  • Whether trastuzumab will provide the same clinical benefit to patients with small, node-negative HER2-positive tumors remains unanswered. The 5 trials lacked the data from which to draw any conclusions in this regard; however, an expert panel at 2007 St Gallen meeting concluded that trastuzumab should not be regarded as standard therapy for women with smaller-than-1-cm, node-negative tumors, especially those with endocrine-responsive tumors.
  • Optimum chemotherapy regimens have not been defined; but, early evidence for non-anthracycline regimens is promising. However until longer follow up or other clinical trial data become available, anthracyclines will continue to be included in chemotherapy regimens for most HER2-positive patients.
  • Trastuzumab is cost-effective but still not affordable for many countries outside of the clinical trial setting.

Dinh P, et al. Nat Clin Pract Oncol. 2008;5(11):645-654.


Proteomic Profiling in Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a heterogeneous disease with numerous genetic aberrations. Currently, AML is classified using the French-American-British (FAB) system (based on lineage differentiation and maturation), as well as flow cytometric analysis of surface marker expression, cytogenetics, and assessment of recurrent molecular abnormalities. However, despite the prognostic relevance of these classification schemes, they typically do not affect therapeutic recommendations. Protein function regulates the phenotypic characteristics of cancer including leukemia; thus, a functional proteomic classification system could provide important prognostic information and could potentially guide the selection of targeted therapies. In previous studies, gene expression profiling has shown promise in providing a new classification schema and to define prognostic subgroups in AML.

Recently, a study was conducted to develop a proteomics-based classification in AML. Reverse-phase protein arrays (RPPA) were used to generate proteomic profiling of the level of expression and activation of apoptosis, signal transduction pathways (STP), and cell-cycle regulating proteins in AML. With this technique proteins and their corresponding phosphoproteins can be assessed, reflecting the activation state and functionality of a given protein (signaling pathway). In the study, a total of 320 samples from 256 newly diagnosed patients with AML (including 97 cases with same-day bone marrow and peripheral blood/pheresis sample) were assayed for 51 total and phosphoprotein epitopes involved in STP, apoptosis, and cell-cycle regulatory pathways.

The following key findings/conclusions are presented:

  • In the subset of patients with same-day blood/pheresis and marrow samples, no biologically relevant differences were observed in protein levels of AML cells between blood and marrow for most proteins (44 of 51), suggesting that either blood or marrow can be used for the protein-expression profiling of AML.
  • Protein expression patterns were independent of clinical characteristics.
  • A subset of 24 proteins showed significant differences in expression levels across the FAB classifications and the patterns of expression easily distinguish purely myeloid subtypes M0, M1, and M2 from M4 and M5 subtypes with monocytic components, and all of these were distinct from erythroleukemia and megakaryocytic leukemia. These data could be helpful in suggesting treatment targets and guide selection of targeted therapies in different FAB subtypes.
  • Expression patterns for AML with cytogenetic abnormalities involving -5 or -7, alone, together, or in combination with -8, were comparable, indicating that different cytogenetic changes have similar effects on protein expression and activation within AML cells.
  • In light of a hypothesis that proteins would form “constellations” (ie, proteins that correlate most closely with each other and suggest certain phenotypes for cells) in which the components provided predictive information, 7 protein signature groups were defined with prognostic information distinct from cytogenetics that correlated with remission attainment, relapse, and OS. Additionally, expression patterns in these groups could be used to suggest combinations of targeted therapies that should be evaluated in combination with conventional treatment.
  • Overall, results from this study show a correlation between protein expression patterns in AML and morphologic features, cytogenetics, and outcome. The advantage of proteonomic profiling over other approaches of classifying AML is that it can provide therapeutic guidance at the same time. The authors noted that a validation study is being conducted with more AML samples that will be assayed with a larger number of antibodies to confirm the findings from this study.

Kornblau SM, et al. Blood. 2009;113(1):154-164.


Long-Term Overall Survival Benefit of Adjuvant Chemotherapy for Colon Cancer: Little Value of Follow Up After 5 Years?

Colon cancer is the third most common type of cancer in both men and women in the US, and it is the second most common cause of cancer-related death. Adjuvant chemotherapy with fluorouracil (FU) and leucovorin has demonstrated improved survival outcomes in patients with colon cancer who are diagnosed at a stage when surgical resection is still possible. Although adjuvant chemotherapy is typically given for only a short period of time (~6 months), it appears to result in long-term benefits (measured based on 3-year and 5-year OS and disease-free survival [DFS] rates).

The Adjuvant Colon Cancer Endpoints (ACCENT) Group analyzed data from 20,898 patients with colon cancer (stage II/III) randomized in 18 phase III trials of FU-based adjuvant therapy to determine the time course of treatment failure and long-term recurrence rates. The endpoints were OS, DFS, and time to recurrence (TTR).

Overall, adjuvant therapy resulted in a 7% improvement in 8-year OS rate (5% in stage II and 10% in stage III patients). In the 8-year follow-up period, hazard rates of OS, DFS and TTR in patients treated with adjuvant chemotherapy never exceeded that of untreated patients, indicating that adjuvant therapy cures some patients rather than delaying recurrence. During the first 2 years post surgery, there is a substantial benefit of adjuvant therapy in reducing the risk of DFS or a recurrence event (HR = 0.61) that diminishes over time and becomes nonsignificant after 4 years, indicating that DFS and recurrence rates are statistically similar after 4 years in patients treated with adjuvant chemotherapy and patients treated with surgery alone. Recurrence rates were <1.5% per year after 5 years and <0.5% per year after 8 years post surgery. Furthermore, patterns of treatment failure over time are quite different for stage II and III patients; patients with stage III disease seem to benefit more from treatment and for a longer period of time.

Observations from this pooled analysis showed a significant DFS benefit with adjuvant chemotherapy, mainly by reducing the recurrence rate within the first 2 years post surgery with some benefit in years 3 to 4, reflecting the curative role of adjuvant chemotherapy. The authors concluded that recurrence rates in patients treated in clinical trials are low after 5 years and minimal after 8 years, suggesting that the value of long-term follow up for recurrence is insignificant.

Sargent D, et al. J Clin Oncol. 2009 Jan 5. [Epub ahead of print]


Modified Response Evaluation Criteria in Solid Tumors

Response Evaluation Criteria in Solid Tumors (RECIST) is the international standard for tumor response evaluation by various means, and is based on measureable disease (ie, the presence of at least 1 measurable lesion). The original RECIST (version 1.0) was published in 2000 by an International Working Group and provided definitions of minimum size of measurable lesions, definitions of targeted/nontargeted lesions, instructions on how many lesions to follow, specified methods of assessment, and provided guidelines for the use of unidimensional instead of bidimensional measurements for overall evaluation of tumor burden. However, a number of questions and concerns have come up that led to the development of modified RECIST (version 1.1). The changes made to RECIST 1.0 are supported by findings from the assessment of a large data warehouse (>6500 patients), simulation studies, and literature reviews.

The following are key changes from RECIST 1.0 to RECIST 1.1:

  • Evaluation of pathologic lymph nodes is included in RECIST 1.1 since lymph nodes are normal anatomic structures, which may be visible by imaging even if not involved by the tumor. Based on the length of the short axis (ie, the diameter typically used to judge if a node is involved by solid tumor) and CT scan as method of assessment, nodes ≥15 mm are considered measurable as target lesions, nontarget lesions (≥10 to <15 mm), or nonpathologic (normal) lesions (<10 mm). The short axis measurement should be included in the sum of lesions in calculation of tumor response.
  • Based on findings from a data warehouse analysis, the number of lesions required to determine overall tumor burden has been reduced from a maximum of 10 to 5 (and from a maximum of 5 to 2 per organ).
  • RECIST 1.1 provides clarification of what is considered progressive disease (PD). In RECIST 1.0, PD was defined as a 20% increase in targeted disease. However, the modified guidelines also require a 5-mm absolute increase to guard against over calling PD when the total sum is very small and PD is within measurement error. Moreover, there is guidance offered on what constitutes ‘unequivocal progression’ of nonmeasurable/nontarget disease, a source of confusion in RECIST 1.0 where PD was considered if there was an increase in any nontarget lesion even when target disease is stable or responding.
  • A section is included to provide guidance on detection of new lesions, including the interpretation of FDG-PET scan assessment.
  • Confirmation of response to ensure responses identified are not the result of measurement error is required only for nonrandomized trials where there is no concurrent comparative control and where response rate is the primary endpoint.
  • Due to the increasing use of PFS as endpoint in phase III trials, more specific guidance is provided on the determination of PD in patients with nonmeasurable disease.
  • A new imaging appendix is included with updated guidance on the use of MRI and PET/CT for optimal anatomic assessment of lesions.

An important question that will be addressed by the RECIST Working Group in the future is whether the anatomic unidimensional assessment of tumor burden can be replaced by either a volumetric anatomic assessment or functional assessment by PET or MRI. This issue was not addressed in RECIST 1.1 since there is presently not enough evidence to recommend adoption of these alternative assessment methods, with the only exception being the use of FDG-PET imaging as an adjunct to the determination of progression.

Eisenhauer EA, et al. Eur J Cancer. 2009;45(2):228-247.


Should an Angiogenesis Inhibitor be Part of Triple-Negative Breast Cancer Therapy?

This clinical update is based on information presented during a satellite symposium organized by PRIME Oncology during the 31st Annual San Antonio Breast Cancer Symposium in December 2008. The pros and cons of including an angiogenesis inhibitor as an adjunct to the treatment of triple-negative disease were discussed by George Sledge, MD, of the Melvin and Bren Simon Indiana University Cancer Center in Bloomington, Indiana, and Jose Baselga, MD, of Vall d’Hebron Institute of Oncology in Barcelona, Spain, respectively.

Triple-negative breast tumors (ER, PR, and HER2 negative) exhibit an aggressive clinical phenotype with a poor prognosis. Proven treatment options are limited, thus, there is a continued need for improved treatment strategies. The microvascular proliferation of triple-negative tumors may serve as a target for angiogenesis inhibitors such as bevacizumab, which targets the VEGF angiogenesis pathway.

Results from 2 large, randomized, proof-of-concept clinical trials (E2100 and AVADO) provided the basis of discussion for this debate. The primary endpoint of both trials was PFS. In the 2-arm E2100 study conducted in the US, patients randomized to paclitaxel plus bevacizumab showed a significantly prolonged median PFS compared with those receiving paclitaxel alone (11.8 months vs 5.9 months, P<.001); however, no significant difference was observed in median overall survival (26.7 months vs 25.3 months, respectively, P = .16) (Miller et al. N Engl J Med. 2007). In the 3-arm, placebo-controlled AVADO study conducted in Europe, the median PFS in the docetaxel plus placebo arm was statistically significant shorter compared with the docetaxel plus bevacizumab 7.5 mg/kg arm (8 months vs 8.7 months, P = .031) and docetaxel plus bevacizumab 15 mg/kg arm (8 months vs 8.8 months, P = .0099) (Miles et al. J Clin Oncol (ASCO Proceedings). 2008).

Key takeaways from this debate are presented:

  • According to Dr Sledge, the significant 6-month improvement in PFS demonstrated with the addition of bevacizumab to paclitaxel in the E2100 trial is “the largest single improvement in PFS that we have seen in a trial in the last generation.” He noted that significant improvements in PFS were also shown in the AVADO study. Furthermore, he explained that the reason for the poor survival outcome in the E2100 study could be attributed to the fact that this study was poorly powered to determine OS and it could only determine a 7-month improvement in OS with P<.05. Bevacizumab-induced toxicities are well known, and manageable hypertension is the most common toxicity associated with this agent. Therefore, Dr Sledge called bevacizumab “an exceptionally well-tolerated addition to a taxane” that induces modest toxicity in the “average patient.” He concluded that adjunct bevacizumab represents a reasonable treatment option for patients with advanced triple-negative breast cancer.
  • Based on Dr Baselga’s interpretation of the E2100 and AVADO results, bevacizumab combined with taxanes have demonstrated positive results in the first-line setting; however, the benefits appear to be marginal in the only placebo-controlled (AVADO) study (although statistically significant, bevacizumab added <1 year PFS versus placebo). Dr Baselga called the outcome of the E2100 study (6-month improvement in PFS without a survival benefit) a “biological effect.” Moreover, he noted that a study conducted with another angiogenesis inhibitor, axintinib, also showed only a 1-month improvement in time to progression (Rugo et al. J Clin Oncol (ASCO Proceedings). 2007), suggesting a consistency between the trials regarding poor outcome. Dr Baselga mentioned that antiangiogenic agents are expensive, and the benefits of these agents are unclear and appear to be minimal in patients with triple-negative disease. He concluded that although he cannot promote the use of antiangiogenic agents outside of the clinical trial setting based on results from these trials, there is a need to continue investigating these agents in breast cancer.
  • Overall, this debate revealed that although angiogenesis inhibitors may be part of the treatment solution, more data are needed to truly understand the benefit of these agents in managing patients with triple-negative breast tumors. Currently, the benefits of adding bevacizumab to standard adjuvant chemotherapy are being investigated in the E5103 trial in breast cancer patients with high risk of recurrence and in the BEATRICE trial in patients with triple-negative breast cancer
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Post Options Post Options   Thanks (0) Thanks(0)   Quote cg--- Quote  Post ReplyReply Direct Link To This Post Posted: 21 Sep 2009 at 4:26pm

I give up cutting and pasting....

 
I was intrigued by Mainy's question regarding the Avastin and Taxol...so I started looking and found this discussion by Dr. George Sledge. (the last article)
 
Connie
 
 
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Post Options Post Options   Thanks (0) Thanks(0)   Quote mainsailset Quote  Post ReplyReply Direct Link To This Post Posted: 21 Sep 2009 at 5:09pm
Connie, very interesting. I was looking too as I've kind of back burner wondered about the sequencing for some time. ps I wrote a long pm to you, black hole of the internets ate it up. Somewhere there is a a bad internet dog with heartburn.
dx 7/08 TN 14x6.5x5.5 cm tumor

3 Lymph nodes involved, Taxol/Sunitab+AC, 5/09 dbl masectomy, path 2mm tumor removed, lymphs all clear, RAD 32 finished 9/11/09. 9/28 CT clear 10/18/10 CT clear
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Post Options Post Options   Thanks (0) Thanks(0)   Quote unklez Quote  Post ReplyReply Direct Link To This Post Posted: 21 Sep 2009 at 5:46pm
Wow so much info to review today. Thank you so much folks.

We definitely think the jury is still out on Avastin and that is the whole reason for the trial.

Will this trial help DW? We don't know. Will it harm her? Maybe but we don't believe the risk is too high given her age and general health and heart health.

As to why T after AC, they are following the standard of care and adding only 1 variable, ie Avastin. That is the key feature of a well designed experiment. Too many variables lead to more conjecture and inconclusive results.

We shall read tonight and comment. Thanks again for sharing all this info.

Unkle

Wife Dx: Jul/09. Age: 37. Grade: High. Size: 3cm. BRCA: -ve. Lumpectomy: Aug/09. Micromet 1/9 node. Chemo Start: Sep/09. Kicked off E5103 (Taxol reaction). Now dd ACB->dd Abraxane. Zometa (S0307).
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Post Options Post Options   Thanks (0) Thanks(0)   Quote unklez Quote  Post ReplyReply Direct Link To This Post Posted: 21 Sep 2009 at 8:38pm
Originally posted by mainsailset mainsailset wrote:

I was wondering if you had pm'd any of the people already on the trial to see how they had fared.....
 
No, we have not. Should we? I am sure that would help but we are not sure how......
 
Originally posted by mainsailset mainsailset wrote:

.....I know from my trial that the BP issue can be very real and wasn't sure if you had already been aware of that side effect......
 
Yes and thanks for the heads-up. The oncologist mentioned that she would monitor the heart closely. The trial sponsor requires the oncologists to monitor the heart (MUGA scan, EKG etc.) much more frequently than they normally would.
 
Originally posted by mainsailset mainsailset wrote:

.....On my trial the Taxol came first together with the Sutent, then followed by AC. Different order. Wondering why your trial will have a different and what the thought process was. With mine they were trying to cut off the source of 'nutrition' to the tumor as quickly as possible, reduce the size then follow with the killer hammer of AC.......
 
This trial is comparing how the addition of Avastin to the standard chemo (AC-->T) works. If they change the order and give T before AC, there will be 1 more variable to think about and that is not a good thing. I am sure they had some good reasons to do it the other way in the trial you went thru'.
 
Originally posted by mainsailset mainsailset wrote:

.....I also saw that the poster had 2nd posted over in the Recurrence thread but didn't check that one out. Could be interesting. I know that one of the members who was posting has since passed away, I miss her in particular as she always had such insight.
 
Not sure what you mean. Could you please explain?
 
 
Wife Dx: Jul/09. Age: 37. Grade: High. Size: 3cm. BRCA: -ve. Lumpectomy: Aug/09. Micromet 1/9 node. Chemo Start: Sep/09. Kicked off E5103 (Taxol reaction). Now dd ACB->dd Abraxane. Zometa (S0307).
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Post Options Post Options   Thanks (0) Thanks(0)   Quote mainsailset Quote  Post ReplyReply Direct Link To This Post Posted: 22 Sep 2009 at 5:28am
Rats, everytime I write a reply it goes into the black hole.
 
You'll see even here that standard of care shows both the protocol of using Taxol before AC or the Taxol after AC. My question is why the switch? We have 2 clinical trials and there is variation between the 2 of them.
 
You can pm any of the posters on the thread I linked to. The Personal Message is just at the top of the menu of page. Also, you could go tothe recurrence menu and search for the thread on the discussion of your trial.
 
It's important to understand, and this is first hand info here, that you need to understand clearly the protocol regarding side effects. Ask onc.
When I had the spike in the BP, I was already monitoring my own BP, I called the doc after hours, relayed the spike that had gone on for 2 days. When I went into the doc's office for weekly visit they were able to change med on that basis. If I hadn't monitored my own, called it in then the protocol called out that they would have to wait another 3 days before making a change. With dangerously high BP that would have been a poor reaction. So monitor yourself all side effects, call them in, and the reported history will give the doctors a better record to respond. Seriously, this is dangerous and having a healthy body to start with is nearly irrelevant when it comes to these drugs, they are powerful.
dx 7/08 TN 14x6.5x5.5 cm tumor

3 Lymph nodes involved, Taxol/Sunitab+AC, 5/09 dbl masectomy, path 2mm tumor removed, lymphs all clear, RAD 32 finished 9/11/09. 9/28 CT clear 10/18/10 CT clear
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Post Options Post Options   Thanks (0) Thanks(0)   Quote unklez Quote  Post ReplyReply Direct Link To This Post Posted: 22 Sep 2009 at 12:13pm
Thanks Manny. Yes we will continue to monitor for the effect on the heart ourselves as well as with the oncologist who was very upfront about the impact to heart. Periodically the oncologist will order MUGA Scan, EKG and BP. Based on your recommendation, we will invest in a personal BP monitor and use it at home daily. If there is any concern, we will be the first to raise hell!

As far as order of giving T vs. AC, all the oncologists we visited recommended the AC-->T when talking about the standard of care option for DW. Your mileage may vary.
Wife Dx: Jul/09. Age: 37. Grade: High. Size: 3cm. BRCA: -ve. Lumpectomy: Aug/09. Micromet 1/9 node. Chemo Start: Sep/09. Kicked off E5103 (Taxol reaction). Now dd ACB->dd Abraxane. Zometa (S0307).
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Post Options Post Options   Thanks (0) Thanks(0)   Quote mainsailset Quote  Post ReplyReply Direct Link To This Post Posted: 22 Sep 2009 at 12:28pm
Sounds good to me, and BTW I also monitored temp at home. I found that once on the course there was just so much to deal with and then chemo brain set in...was just hard to track everything. I ended up carrying a daily diary with me so I could know for sure if I took my meds...know what my temp was doing because I simply could not remember everything.
 
I also ended up using Google Calendar. I have a Google account and discovered they had a calendar you could set up, one that could be shared with family or friends if you so choose, and I put all kinds of info in there. Google also has a med page where you can list the meds you're on, and organize things. It helps when you've got this sack of meds to sort through. Oh, and a life saver, I taped on top of each pill bottle what the med was for cause Lord knows after awhile there were too many and I couldn't take the chance of mixing them up.
 
So happy that you were able to get into the study and hoping that you'll be one of the non placebo participants!
dx 7/08 TN 14x6.5x5.5 cm tumor

3 Lymph nodes involved, Taxol/Sunitab+AC, 5/09 dbl masectomy, path 2mm tumor removed, lymphs all clear, RAD 32 finished 9/11/09. 9/28 CT clear 10/18/10 CT clear
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Post Options Post Options   Thanks (0) Thanks(0)   Quote unklez Quote  Post ReplyReply Direct Link To This Post Posted: 12 Oct 2009 at 5:40pm
DW got her second AC+B today. Uneventful except sinus pressure from C.
Wife Dx: Jul/09. Age: 37. Grade: High. Size: 3cm. BRCA: -ve. Lumpectomy: Aug/09. Micromet 1/9 node. Chemo Start: Sep/09. Kicked off E5103 (Taxol reaction). Now dd ACB->dd Abraxane. Zometa (S0307).
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