MSKCC OncoNotes Conference Highlights

New Diagnostic Technologies: Evaluation and Integration into Clinical Care

Tiffany A. Traina MD — Sat, 10 Oct 2009 13:55:40 +0000

Post by: Tari King, MD; Tiffany A. Traina, MD; Conleth Murphy, MD
Post from: ASCO Breast Cancer Symposium

The potentials and pitfalls of new diagnostic technologies were stunningly reviewed in a lively panel discussion by Dr Alfred O. Berg from EGAPP (Evaluation of Genomic Applications in Practice and Prevention), Dr Robert L. Becker form the FDA, and Dr Daniel F. Hayes from the University of Michigan which provoked considerable audience interest. Discussion centered on the need for evidence-based implementation of emerging molecular tests, and the varied panel of speakers (representing federal, independent evaluation and clinical viewpoints) provided at times contrasting opinions on this topic. All speakers agreed that prospective studies are the ideal way to investigate emerging technologies although well-designed “retrospective-prospective” analyses of good quality trials may be an acceptable alternative.

Controversies in the Management of the Axilla

Tiffany A. Traina MD — Fri, 09 Oct 2009 13:54:18 +0000

Post by: Tari King, MD; Tiffany A. Traina, MD; Conleth Murphy, MD
Post from: ASCO Breast Cancer Symposium

Controversies in the management of the axilla were highlighted on Friday in General Session VI. The role of axillary ultrasound in the clinical assessment of patients with early stage breast cancer was discussed by Dr. Baruah (abstract # 22). In their series of 274 pts undergoing breast conservation therapy the routine use of axillary US followed by preop FNA in patients with sonographically suspicious lymph nodes, spared 17/57 (29.8%) node positive patients unnecessary sentinel node biopsy. Axillary US and FNA was highly accurate (84%) in patients with macrometastases yet was unable to detect micro-metastatic disease. The importance of “minimal lymph node disease” and whether or not there is a subgroup of patients with a positive SLN who can be spared a completion axillary dissection remains uncertain. Dr. Mamounas reviewed the recent results from the MIRROR study (JCO 2009) which demonstrated a significant increase in axillary recurrence for patients with micrometstatic disease in the SLN who do not undergo completion axillary node dissection or axillary radiotherapy. However, it is important to note that this result may be confounded by the lack of systemic adjuvant therapy used in this cohort. We await data from the IBCSG 23-01 and NSABP B32 trials to further address the role axillary dissection on outcome for patients that have limited disease in the SLN.

Maximizing Local Control

Tiffany A. Traina MD — Fri, 09 Oct 2009 13:51:05 +0000

Post by: Tari King, MD; Tiffany A. Traina, MD; Conleth Murphy, MD
Post from: ASCO Breast Cancer Symposium

With regards to local-regional therapy Chen et al. reported their single institution results comparing the efficacy of three forms of accelerated partial breast irradiation (APBI) at William Beaumont Hosptial (abst # 210). In their group of 373 patients selected for APBI based on age, histology, margin and lymph node status the 5-yr actuarial local recurrence rate was 1.7% with no difference between the 3 APBI modalities [1.6% interstitial HDR/LDR, 1.1% 3-D conformal external beam, 2.6% Mammosite]. The median follow up was 6.4 years with longer follow up among interstitial HDR/LDR patients (9.7yrs) as compared to the other two treatment modalities, 4.2yrs for 3-D CRT and 4.1 yrs for MS respectively. Continued follow-up among these groups, particularly for 3-D CRT and MS, will be needed to assess the long term equivalency of these 3 APBI modalities. In a nice review of the topic, Dr. Moran a Radiation Oncologist from Yale University highlighted the importance of adhering to the ASTRO guidelines when considering APBI in clinical practice.

Data supporting the importance of tumor intrinsic subtype in local regional therapy outcomes continues to emerge. Dominici et al (abstract #74) demonstrated that tumor subtype as measured by the IHC surrogates (ER,PR,Her2) was a prognostic factor for LRR after mastectomy with our without PMRT. In the absence of PMRT, nodal burden, luminal B (HR 4.26, CI 1.05-17.33, p =0.04) and basal phenotype (HR 13.87, CI 4.96-38.8, p=0.015) predicted for worse LRR-free survival whereas in the presence of PMRT, only basal subtype (HR 9.47, CI 1.85-48.36, p= 0.007) was associated with significantly worse LRR-free survival on MVA. Dr. Marc van de Vijver from the Netherlands group also reviewed their efforts to identify molecular markers predicting for local control. Finally, with respect to PFS and OS, Ellis et al (abstract #33) presented data suggesting that the PAM50 qRT-PCR gene expression classifier is highly prognostic among patients with estrogen receptor positive disease treated with tamoxifen and was superior to IHC classifiers and he Adjuvant! Online tool in this group.

Personalized Medicine

Tiffany A. Traina MD — Fri, 09 Oct 2009 13:49:47 +0000

Post by: Tari King, MD; Tiffany A. Traina, MD; Conleth Murphy, MD
Post from: ASCO Breast Cancer Symposium

Personalized medicine was a central topic of the featured oral abstracts at the Symposium. Abstract #128 described a specific germline mutation of CHEK2 which encodes a protein involved in the DNA damage response. This deletion (CHEK2*1100delC) has previously been shown to increase breast cancer risk and was now associated with decreased breast cancer specific survival and increased risk of developing second primary breast cancers. Abstract #1 described three common single nucleotide polymorphisms in 160 women with a strong family history but without a personal history of breast cancer. The authors concluded that information about these common polymorphisms could change the risk assignment of a significant proportion of patients. While neither of these findings have immediate clinical relevance, they reflect the increasing interest in identifying genetic markers (germline and somatic) of risk, prognosis and treatment response.

New Targets, New Drugs

Tiffany A. Traina MD — Fri, 09 Oct 2009 13:48:31 +0000

Post by: Tari King, MD; Tiffany A. Traina, MD, Conleth Murphy, MD
Post from: ASCO Breast Cancer Symposium

A highlight of the symposium was a session titled “New targets, New drugs”, which reviewed current state of the art targeted therapies and discussed potential future directions. Dr. Antoinette Tan reviewed the promising preclinical and clinical data for PARP inhibitors in patients with BRCA mutations and with triple negative breast cancer. MSKCC is participating in a large multicenter phase III study evaluating the efficacy of PARP inhibition in combination with gemcitabine and carboplatin for patients with triple negative disease. Dr. Shanu Modi from MSKCC discussed inhibitors of HSP90, a molecular chaperone that helps to protect HER2 from degradation within the cell. She described the encouraging data for this class of drugs in HER2-positive advanced breast cancer that has been refractory to trastuzumab-based therapies. In addition, the work of Dr Gabriela Chiosis of MSKCC was highlighted. She has developed a “next-generation” HSP90 inhibitor by modifying the chemical structure in order to improve efficacy and minimize toxicity, with compelling pre-clinical activity. Dr. Suzanne Fuqua described potential mechanisms of resistance to endocrine therapy, including activation of companion growth factor receptors and downstream signaling pathways such as that of the androgen receptor. Building on the preclinical work of the late Dr. William Gerald, Dr. Traina at MSKCC is leading a multicenter trial targeting the androgen receptor in patients with ER/PR-, AR+ breast cancer. Finally, Dr Hope Rugo described the many agents being evaluated as inhibitors of angiogenesis and discussed rational combinations of these agents with chemotherapy and/or other biologics.

Bone Health and Breast Cancer

Tiffany A. Traina MD — Thu, 08 Oct 2009 13:46:13 +0000

Post by: Tari King, MD; Tiffany A. Traina, MD; Conleth Murphy, MD
Post from: ASCO Breast Cancer Symposium

A General Session discussed issues of bone health in the context of breast cancer. ASCO Guidelines for assessment and maintenance of bone health were reviewed. Dr. Joseph Lane, an orthopedist from the Hospital for Special Surgery discussed surgical options for the management of skeletal complications related to bone metastases or osteoporosis. Denosumab (a fully-human, monoclonal antibody to RANK ligand) was superior to zoledronate in delaying or preventing skeletal related events in women with metastatic breast cancer in a recent phase III study presented at the ESMO meeting in September 2009. Similar rates of osteonecrosis of the jaw were seen with both agents. Bisphosphonates have been shown to reduce AI-associated bone loss, however, their potential role to reduce the risk of breast cancer recurrence remains under investigation. Results of several prospective adjuvant trials (ie, AZURE and NSABP B34) are eagerly awaited.

Challenges in Survivorship

Tiffany A. Traina MD — Thu, 08 Oct 2009 13:44:08 +0000

Post by: Tari King, MD; Tiffany A. Traina, MD; Conleth Murphy, MD
Post from: ASCO Breast Cancer Symposium

The survivorship needs of patients with a history of breast cancer were recognized as an important theme. Bardia et al described that the 10 year risk of a cardiovascular event is greater than or equal to the 10 year risk of breast cancer recurrence in 78% of postmenopausal patients with early stage breast cancer receiving adjuvant endocrine therapy (abstr #133). Investigators urged physicians to manage the cardiovascular risk factors affecting our patients, specifically hypertension, as cardiac deaths are the second leading cause of death for cancer survivors. Review of the WINS, WHEL and WHI trials examining dietary interventions concluded that data are inconsistent and there is no agreement about the optimal diet for breast cancer management. Observational and retrospective data support the benefit of exercise in improving quality of life and reducing risk of breast cancer recurrence, although prospective randomized trials with a survival advantage are lacking. Vitamin D deficiency is a recently recognized problem with regards to bone health; supplementation is easily achieved and of benefit in maintaining bone strength. However, the role of vitamin D is controversial with regards to the impact of low levels on breast cancer outcomes.

Poster Discussion Section: Systemic Management

Tiffany A. Traina MD — Thu, 08 Oct 2009 13:36:19 +0000

Post by: Tari King, MD; Tiffany A. Traina, MD, Conleth Murphy, MD
Post from: ASCO Breast Cancer Symposium

Prior to the Symposium there was very little data concerning the issue of whether or not women with small, lymph node negative, HER2-positive breast cancers derive benefit from adjuvant trastuzumab. McArthur and colleagues from MSKCC reported results of a retrospective study comparing the management and outcomes of HER2+, T1N0 tumors in the trastuzumab and pre-trastuzumab era (abstr #228). Of the 256 cases reviewed, more than one-third of patients had subcentimeter tumors. Baseline characteristics between cohorts were similar with the exception of chemotherapy use, which was greater in the trastuzumab-era patients. After 4 years of followup, patients with small, node-negative, HER2+ breast cancers had excellent outcomes following adjuvant chemotherapy with trastuzumab with 3 year DFS 100% and OS 99%. This strongly suggests a major impact of trastuzumab therapy in these patients.

Safety and efficacy after 6 years of followup were reported for the neoadjuvant, randomized trial comparing paclitaxel followed by FEC, with or without concurrent trastuzumab in patients with HER2+ breast cancer (abstr #221). No clinical cardiac toxicity events have occurred in patients receiving anthracycline and trastuzumab during this long-term followup period. The overall survival advantage to trastuzumab in the setting of anthracycline/taxane chemotherapy was maintained at 6 years (84% vs. 100%, p=0.035).

Welcome to MSKCC OncoNotes from the 2009 ASCO Breast Cancer Symposium

MSKCC Doctors — Thu, 08 Oct 2009 00:00:18 +0000

Tiffany A. Traina, MD, Tari King, MD, and Conleth G. Murphy, MD from the Memorial Sloan-Kettering Cancer Center Breast Cancer Medicine Service will blog from the 2009 Breast Cancer Symposium, providing coverage and analysis of key sessions along with implications for standards of care.

Lung Cancer: Poster Discussion Session and Oral Abstracts, Monday June 1st

M. Catherine Pietanza, MD — Tue, 02 Jun 2009 22:58:00 +0000

Post by M. Catherine Pietanza, MD:

Once again, a common theme in the treatment of NSCLC was that molecular characterization is necessary and will assist in directing the appropriate therapies toward our patients.

Multiple presentations showed the ability of using molecular markers to guide patient selection for trials, of which I will provide a few examples. The North-East Japan Gefitinib Study Group presented phase III data where 198 patients with newly diagnosed, advanced NSCLC and EGFR activating mutations were randomized to receive either gefitinib or carboplatin/paclitaxel (Abstract #8016). The results of this trial are impressive and show that the response rates and median progression free survival for patients randomized to gefitinib compared to those receiving chemotherapy were 75% and 10.6 months versus 29% and 5.5 months, respectively. This study validates the use of EGFR tyrosine kinase inhibitors in the first line setting for patients with activating mutations. Several other studies based patient eligibility upon the presence of activating EGFR mutations (Abstracts #8013, #8023, #8026). In a phase II study using salirasib, which inhibits RAS binding to plasma membrane and blocks RAS-dependent cell growth, Johnson et al. demonstrated that K-RAS selective trials are feasible (Abstract #8012). These data underscore the importance of genotyping NSCLC, as has become a standard at our institution.

Two abstracts showed that biopsying patients upon progression of disease was safe and feasible. The BATTLE study presented by Kim et al. at MD Anderson Cancer Center demonstrated that rebiopsy allowed for the identification of biomarkers prospectively, the results of which directed patient treatment in various available protocols (Abstract #8024). Similarly, Dr. Arcila and colleagues at Memorial Sloan-Kettering Cancer Center showed that patients can be rebiopsied when they no longer respond to EGFR tyrosine kinase inhibitors to determine the patterns of resistance and guide decision making for further targeted therapies (Abstract #8025).

A few important points were garnered during the oral presentations focusing on local-regional and adjuvant treatment for NSLC. Updated survival analysis of JBR.10, the randomized phase III study comparing cisplatin/vinorelbine to observation in patients with resected stage IB and II was presented (Abstract #7501). After a median follow-up of greater than nine years, survival analysis continues to show a benefit for adjuvant chemotherapy (HR 0.78 with p = 0.04), which is primarily in patients with stage II disease. Adjuvant chemotherapy for patients with stage IB remains controversial, although there is a trend toward improved outcomes for those with large tumors. Importantly, in early stage disease, biomarkers also may be able to predict benefit from adjuvant chemotherapy, as demonstrated in the study presented by Dr. Fouret (Abstract #CRA7502). Here, tissue samples of patients that had participated in the IALT trial were studied in a retrospective manner and MSH2 was identified as a predictive marker. Further studies are warranted to prospectively analyze biomarkers, which are underway.

A phase II study comparing pemetrexed, carboplatin, and concurrent thoracic radiation with or without cetuximab (CALGB 30407) showed that this regimen is safe and effective, with both arms meeting a predefined threshold of median survival of 20.9 months (Abstract #7505). However, the addition of cetuximab did not benefit outcomes. Further, there was a trend toward better outcomes observed with non-squamous NSCLC. The results of this work are being used to launch two large phase III studies, one of which will contain a pemetrexed arm in non-squamous NSCLC and another will address the use of cetuximab. The RTOG 0214 study attempted to evaluate prophylactic cranial irradiation (PCI) in patients that had completed treatment for locally advanced disease (Abstract # 7506). The study did not meet its target accrual and closed early, thus was not able to show benefits in outcomes. It demonstrated that PCI decreased the incidence of CNS metastases in this group of patients. Quality of life data will be presented later in the year.

In small cell lung cancer, treatment options continue to be limited. Several abstracts showed that the standard of care for first line treatment of extensive stage SCLC remains etoposide/platinum in the US and Europe, whereas in Japan it is irinotecan/platinum (Abstracts #8027 and #8029). In the second-line setting, amrubicin was compared to topotecan in a randomized phase II trial for patients with relapsed sensitive SCLC and found to have significantly improved response rate and a trend toward improved survival (Abstract #8028). Similarly, amrubicin shows response in those patients with refractory disease (Abstract #8103).

This marks the end of the lung cancer presentations at ASCO 2009. I hope you found these summaries helpful.