Patient Reported Outcomes, Genetics, and Social Media
Dr. Sarah Hawley
ASCO 2015 had some very interesting sessions covering patient-reported outcomes, decision-making and general health services use. A few highlights from sessions that I attended:
— A session called The Learning Health Care System: using big data to inform clinical decision making (5/30 Health Services Research – HSR track). Speakers talked about the use of the SEER registry and plans to link SEER data with patient information on genetics and genomic test results (Penberthy). Dr. Shilsky from ASCO discussed plans for launching ASCO Cancer LINQ. Dr. Ann Marie Meyer talked about big data initiatives at the University of N. Carolina. As a whole, the session informed the audience about future plans to be able to study and hopefully improve cancer care through various programs that will capture and analyze cancer data.
Several papers in the Health Services Research and Quality Care oral session focused on breast cancer care.
— A paper by Helzlsouer described the results of a small RCT of an intervention (the TENS study) to improve adherence to systemic therapy in low income women with breast cancer; the results suggest that a navigator plus computer program was effective for reducing refusals for chemotherapy or endocrine therapy. http://abstracts.asco.org/156/AbstView_156_145724.html
— Rocuque described a program in and around Alabama that provides navigation services to all cancer patients, including those with breast cancer. The authors showed that patients who were navigated (which involved assisting with appointment scheduling and self management) had lower use of emergency room and other services than those not navigated. http://abstracts.asco.org/156/AbstView_156_150989.html
— Lipitz Snyderman presented a study showing that habits of surgeons/providers may influence what testing patients receive. In this work, the authors found that patients were more likely to receive imaging when the patient before them received it, in the context of imaging in breast cancer. http://abstracts.asco.org/156/AbstView_156_151771.html
— Kurian presented data from the iCanCare study (a large population based survey of breast cancer patients in LA and Georgia) looking at use of second medical oncology opinions (SMO), and factors associated with SMOs. The authors found that use of SMOs was rather low, but that use of online communication and social media was associated with SMO use. http://abstracts.asco.org/156/AbstView_156_149234.html
There were a lot of presentations on genetic testing this year, given the increase in use of gene panel testing. May focused specifically on breast cancer. One interesting session was called Genetic Testing in 2015: Who Owns the Data, How Do You Return Results, and Other Clinical Dilemmas. This session talked about the impact of genetic panel testing, and a genetic counselor spoke about the importance of pre-test counseling to educate patients and especially to manage expectations about the results of testing (and what to do with indeterminate results). Dr. Mark Robson discussed that the ability to “act with clarity” on the results of genetic panel testing becomes very difficult, beyond BRCA1/2 results (that is, other than BRCA 1/2 results, it is not always clear what to recommend or tell patients). There were several other interesting discussions on genetic testing, focusing primarily on the use of genetic panel testing. Another great session that included 3 papers and 3 discussants on various issues related to genetic panel testing was a Clinical Science Symposium: A Tale of Two Genomes: Interpreting Somatic and Germ-Line Sequencing Results Together
These abstracts were all very interesting, and the session was worth attending because the discussant for each abstract did a wonderful job of adding to the discussion around genetic panel testing.
Another interesting discussion was held during the HSR poster session on the use of online communication, social medical and disease specific hash tags, and use of email communication by patients vs. physicians.
Global Cancer Control
This was an exiting ASCO Annual meeting for those of us passionate about reducing global disparities in cancer – most new cases and two thirds of all cancer deaths occur in low- and middle-income “developing” countries. ASCO has taken steps to encourage discussion and to raise the profile of this previously neglected area of global health. The following are highlights from global oncology activities at ASCO 2015:
Friday, May 29 –1-545 pm S100 Special Session (p38 of ASCO schedule): Global Oncology Symposium – Gabriel Hortobagyi co-chair, Yun Yen, Taipei Medical University co-Chair: Dr David Kerr, Oxford-based inaugural editor-in-chief of the new ASCO Journal of Global Oncology, gave an overview of the discussions which led to the creation of this unique journal. The Journal of Global Oncology will give researchers in developing countries a much needed opportunity to share their work, and for scientists in all world regions to showcase their research in areas often neglected by other cancer research journals, such as in a advocacy and implementation science.
The first half of the Global Oncology Symposium was focused on gastric cancer and “East/West differences” in the location of tumors, biology, and survival. The second half was more relevant to cancer control policy, and included an excellent overview of the cancer -and health systems aspects to cancer control by Dr Anil d’Cruz, from the Tata Memorial Cancer Centre, Mumbai, India. Dr d’Cruz presented national and state-led efforts to improve access to quality care including oral cancer screening within primary care, and described the “National Cancer Grid”. Another highlight of the Symposium was the superb talk by Dr Gilberto Lopes (@GlopesMd), a medical oncologist from Sao Paulo Brazil, and a faculty member at the Johns Hopkins University in Baltimore, Maryland. Dr. Lopes presented on the remarkable international effort led by the Union for International Cancer Control (UICC, Geneva) to advise the World Health Organization on updating the cancer medicines section of the WHO Essential Medicines List. A detailed account of this work and the revised list of medicines which was ultimately approved for inclusion in the WHO EML can be seen here http://www.uicc.org/advocacy/our-campaigns/essential-medicines and http://www.who.int/selection_medicines/committees/expert/20/en/ .
Saturday May 30 was the inaugural editors and editorial board meeting for the new ASCO Journal of Global Oncology.
Saturday evening was the side-event for AORTIC, the African Organization for Research and Training in Cancer. For updates on AORTIC including their next (biannual) meeting in Marakkesh, Morocco November 2015 please see http://www.aortic-africa.org.
Supportive Care and Patient Care
Dr. Matt Katz
Many women with metastatic breast cancer get a monthly dose zolendronate, or Zometa, for bone metastasis to keep bone healthy and strong. A randomized trial from Alliance, CALGB 70604, will change that. The study randomized 1822 patients with breast, prostate cancers or multiple myeloma to zolendronate monthly vs. every three months for two years. Patients getting zolendronate every three months did just as well overall. There was a slightly higher risk of needing bone surgery but no difference in skeletal events, need for radiation and a trend toward less zolendronate-caused jaw injury. The discussant, Dr. Jamie von Roenn, commented that as the 3rd trial with these results, CALGB 70604 confirms that every three months is enough.
We’ve discussed a lot on #bcsm about the cognitive effects of chemotherapy. Dr. Michelle Janelsins presented data from NCORP multicenter study looking at 366 breast cancer patients and possible biologic markers of ‘chemobrain’, more formally called chemotherapy-related cognitive impairment (CRCI). They were compared to controls (people without cancer).Patients did worse with all measures after chemotherapy compared the control group: word association, word recall, verbal memory and backward counting. Decreases in executive function were associated with increases inflammatory markers/cytokines IL-1β, MCP-1 (both p < 0.05). The author tried to suggest an association between neurotransmitter signaling and CRCI, but it didn’t make the statistical cut of p-value <0.05. Overall it suggests that inflammation may play a role in development of CRCI, less clear on neurotransmitter signaling. Both areas for possible targeting drugs to avoid chemobrain, but that will require more work.
Lastly, a very interesting study presented by Dr. Karen Mustian demonstrated that exercise really may help lessen cognitive impairment. A phase 3 trial randomized people with non-metastatic cancer [84% breast cancer patients] to either standard care or an individualized exercise low-moderate intensity program called EXCAP done daily for 6 weeks. The abstract says 479 people but she presented it as 619 evaluable patients. All patients (100%) in the EXCAP exercise group were able to walk daily. Patients who exercised had less cognitive impairment, less decline in quality of life. Biologic markers showed that pro-inflammatory markers decreased, IL-6 and IL-10 increased for exercisers strongly suggesting exercise decreases inflammation. The analysis fell just shy of showing a link between the inflammatory changes and cognitive impairment, but the take-home is regardless of the means, the end result is less side effects from chemotherapy by exercising even at low-moderate intensity.
Metastatic Breast Cancer
Dr. Don Dizon
For women with metastatic breast cancer, progress has been made by emphasizing the concerted efforts to evaluate treatments in subgroups rather than designing trials for “all-comers”.
For women with hormone receptor-positive breast cancer, a new standard of care is available for those who have progressed after one prior line of endocrine therapy. The PALOMA3 trial population consisted of over 500 women (79% postmenopausal) with advanced breast cancer (almost 60% with visceral disease) who were randomly assigned to treatment with the CDK4/6 inhibitor palbociclib plus fulvestrant (PF) or placebo plus fulvestrant (PlF). As reported in the New England Journal of Medicine, PF resulted in a significant improvement in PFS (9 versus 3.8m, respectively, HR 0.42; 95% CI .32-.56). Importantly as well, there was no increased safety signals noted and global quality of life was maintained with PF, but the investigators reported deterioration during the study period among women treated with PlF.
An additional trial, CALGB 40503, evaluated whether the addition of bevacizumab to letrozole provided additional benefit. While a significant PFS advantage was noted (20 vs 16m, HR 0.75, p=.016), there was no advantage in overall survival.
For women with HER2-positive breast cancer, the most important news was the negative study results of the MARIANNE clinical trial (Ellis, Abstr 507). In this trial, 1095 women with HER2+ metastatic breast cancer, previously untreated in the metastatic setting (31% of whom had prior neoadjuvant or adjuvant HER2 treatment) were randomly assigned to T-DM1 (T) or T-DM1 plus pertuzumab (TPz) or to the standard arm of trastuzumab plus paclitaxel (TrP). With a median of 35 months, there was no difference in the arms in PFS (median, 14, 15, versus 14 months, respectively) or the overall response rate (60, 64, and 67%).
For women with triple-negative breast cancer, (TNBC) there was some encouraging news though none of them will change practice immediately. Tiffany Traina from Memorial Sloan-Kettering Cancer Center presented data using the androgen receptor inhibitor, enzalutamide, for women with metastatic TNBC, 40% of whom are AR positive (Traina, Abstr 1071). Although the overall response rate to daily oral dose enzalutamide was only 8%, sustained clinical benefit at 16 weeks was 35% with almost 30% continuing to derive treatment benefit at 24 weeks. The Median PFS was over 4 months. In addition, a separate poster looked at the predictive ability of an AR gene expression signature (Parker, Abstr 1083) and suggested that it could be used to identify patients most likely to benefit from treatment. Those with this AR signature also were found to have an almost doubled PFS (median 16 versus 8 weeks).
A second trial looked at a novel immunoconjugate, IMMU-132, which is a conjugate of humanized anti-Trop2 monoclonal antibody with the cytotoxic agent, SN-38 (Bardia, abstr 1016). In this phase I/II trial, 48 patients with pretreated TNBC (median of 4 prior lines of theray) were treated on a two-week on/one week off schedule. The primary toxicity was febrile neutropenia in 30% of patients, but otherwise, less than 5% of patients experienced serious toxicities. The overall response rate was 21% with almost 40% experiencing a clinical benefit at six months.
Finally, some data were presented on the role of PARP inhibitors in breast cancer. While olaparib is FDA approved, it should be noted that the label is restricted to recurrent ovarian cancer and does not include the indication for breast cancer. Hence, further work is needed in women with breast cancer. In one interesting trial, a phase I study was conducted of the PARP inhibitor, veliparib, with weekly carboplatin and weekly paclitaxel (Pahuja, Abstr 1015) in 30 patients (22 of whom had TNBC). Among women with TNBC, the response rate to this 3 drug combination was 52% and interestingly, the response rates did not differ significantly among women with or without a BRCA mutation (ORR was 60 and 67% in BRCA positive and negative patients, respectively).
Other important data apart from therapeutics included the following important findings:
— Treatment with zoledronic acid for bone metastases is fine using an every 12-week rather than an every 4 week regimen (Himelstein, Abst 9501)
— A scalp cooling system can effectively prevent hair loss among women on chemotherapy. (Rugo, Abstr 9518)
— Copper deficiency using tetrathiomyolybdate (TM) may have a role in preventing metastases, which may have implications for women with more advanced disease (Nackos, Abstr 11008).
As far as immunotherapy, there was no significant data presented related to breast cancer. However this is an area of active interest and ongoing clinical trials may help define how to use these drugs, such as checkpoint inhibitors. As an example, Emens, et al. presented a study at the AACR 2015 meeting looking at the PD-L1 inhibitor, MPDL3280A in women with TNBC. Among 21 evaluable patients, the ORR was 19% with 2 CR reported. These early data require further study but hopefully, will point the way forward for us in the use of the immune system for women with metastatic disease.
Dr. Anees Chagpar
There was a lot of talk about breast cancer surgery at ASCO this year – and many tremendous studies were presented.
Sagara et al used SEER to evaluate whether surgery was necessary for low grade DCIS. Surgery was associated with improved overall and disease specific survival for DCIS – except in the low grade subset. Monica Morrow in her discussion noted that this was based on 63 patients at 10 years of follow up, and that for over 20% of patients with DCIS, there is concomitant invasive cancer. Furthermore, in the EBCTG Overview, patients with low grade DCIS treated with excision alone had a 30% in-breast recurrence rate at 10 years, half of whom were invasive. Perhaps the “final answer” about the acceptability of observation alone for low grade DCIS will come from the LORIS trial.
Mehra Golshan presented work from the CALGB 40603 and 40601 for women with triple negative and her2 positive cancers treated with neoadjuvant therapy. While the study showed that, in those in whom breast conserving surgery was attempted, surgeons were successful at achieving negative margins in 88%. However, the main question that came out of this study was “why are so few patients getting breast conserving surgery following neoadjuvant chemotherapy?”. There were a few issues – to begin with, as Morrow pointed out, imaging and physical exam do not reliably distinguish viable and non-viable tumor such that 28% of patients with a pathologic complete response were felt not to be good candidates for breast conserving surgery. And then of course, there is patient choice – 28% of patients eligible for breast conserving surgery chose to have mastectomy.
Patient choice was a big factor in another study by Jagsi et al, who looked at patients’ decision-making regarding contralateral prophylactic mastectomy (CPM). Nearly half of the 1949 patients with unilateral breast cancer who responded to the iCanCare survey considered CPM; but only 37% of these women knew it did not improve survival, and 23% felt that it did. Roughly 20% of women at average risk opted for CPM, and the vast majority of these did so for peace of mind. One of the things that came out loud and clear in this study was the importance of physicians having clear discussions about the pros and cons of CPM.
And then, there was (what for me at least) was the highlight of ASCO. I had the good fortune to be able to present the initial findings of the SHAVE trial – a prospective randomized controlled trial of routine cavity shave margins vs. standard partial mastectomy with or without selective margin excision. We found that, with the simple technique of taking cavity shave margins at the time of the initial surgery, we could reduce positive margins and re-excision rates by 50%, without compromising patient reported cosmetic outcomes, nor increasing complication rates. Our findings were published in the New England Journal of Medicine, and released open-access online the morning of our presentation.
It was an ASCO I will never forget….
Neoadjuvant and Adjuvant Therapy
Dr. Julie Gralow
Abstract # LBA500 (RG Margolese et al) – Endocrine agents in DCIS
Ductal carcinoma in situ (DCIS), also known as non-invasive or stage 0 breast cancer, is generally identified by screening mammography. Because it is not-invasive, the chance of a distant recurrence and death from DCIS is almost zero. Some DCIS may ultimately progress to invasive cancer and therefore it is the current standard of care to remove DCIS with mastectomy or lumpectomy. A prior study, NSABP B-24, showed that tamoxifen could reduce the chance of a breast cancer recurrence in DCIS patients following lumpectomy and radiation. In early stage invasive breast cancer, the aromatase inhibitors have been shown to be superior to tamoxifen in reducing breast cancer recurrences and second breast cancers in postmenopausal women. The NSABP B-35 trial compared tamoxifen with an aromatase inhibitor in DCIS patients undergoing lumpectomy. B-35 enrolled 3,104 postmenopausal patients with estrogen receptor (ER)-positive DCIS who had undergone lumpectomy. Patients were expected to receive breast radiation, and were randomized to 5 years of either tamoxifen or the aromatase inhibitor anastrozole (Arimidex). The primary endpoint of the B-35 trial was the “breast cancer free interval” (any subsequent breast cancer event, including local, regional or distant recurrence or a second DCIS or invasive breast cancer in either breast). At 10 years, 93.5% of patients receiving anastrozole had not had a breast cancer event, and 89.2% receiving tamoxifen had not had an event. The difference between the 2 anti-estrogen drugs seemed to be most significant in women < age 60, with no statistical difference seen in those > 60 years of age. Almost identical numbers were seen for breast cancer events occurring in the same breast as the original DCIS (ipsilateral recurrence) as compared to the opposite breast (contralateral recurrence), suggesting that these drugs were working mainly as “chemoprevention” to reduce the chance of developing a second breast cancer. There were more uterine cancers and blood clots in the tamoxifen arm, and more fractures and joint aches in the anastrozole arm. There was no difference in deaths between the two drugs. The conclusion was that anastrozole was more effective than tamoxifen, had an acceptable safety profile, and is a preferable option for treating postmenopausal women (presumably those < 60) with ER+ DCIS. Since endocrine agents do not reduce deaths in DCIS patients (there are virtually no breast cancer deaths due to DCIS), because the majority of women will not have a second breast cancer event, and because these drugs cause side effects, a careful evaluation of the expected benefits and risks should be undertaken when considering taking these drugs for DCIS. Endocrine agents should be considered an OPTION to reduce risk of a subsequent breast cancer after a diagnosis of DCIS.
Abstract 503 (J Gralow et al) – Comparison of adjuvant bisphosphonates to reduce bone metastasis
Bone is the most common site of distant recurrence in breast cancer. Previous studies suggest that bisphosphonates, drugs that decrease bone breakdown commonly used to treat both osteoporosis and bone metastases, can reduce bone recurrences and deaths in early stage, postmenopausal breast cancer patients. The SWOG S0307 study compared 3 different bisphosphonates given for 3 years, intravenous zoledronic acid (Reclast, Zometa), oral ibandronate (Boniva) , and oral clodronate (Bonefos), to determine if the more potent, newer generation drugs would have a bigger effect on preventing breast cancer recurrences. Patients with stage I-III breast cancer who were receiving chemotherapy and/or endocrine therapy were eligible for the study. No difference was seen between the 3 drugs – disease-free survival (being alive without a recurrence) at 5 years was 88% in all 3 arms and 5-year overall survival (being alive) was 93% in all 3 arms. Overall toxicity grade was low and differed little across the 3 arms, although the oral drugs clodronate and ibandronate caused more gastrointestinal symptoms, and higher pain was reported for zoledronic acid and ibandronate. Osteonecrosis of the jaw (non-healing, exposed bone), a rare complication of this class of drugs, was highest with zoledronic acid (1.27%) and lowest with clodronate (0.31%). Women undergoing treatment for breast cancer are at increased risk of osteoporosis, and these agents have previously been proven to decrease bone loss and fracture. In S0307, fractures were equal in all 3 arms. About 5% of patients had a fracture at 5 years, about half of what would be expected in a similar population of breast cancer patients not receiving bisphosphonates. Patients were asked whether they would prefer an oral or an intravenous drug if all 3 proved to be equal in efficacy. About 75% said they would prefer an oral drug. Unfortunately, only the intravenous drug zoledronic acid is available in the U.S. Oral clodonate is approved in many other parts of the world to treat bone metastases, but not in the U.S. Ibandronate is available as a monthly oral osteoporosis drug in the U.S., but not at the daily dose studied in S0307 that is used to treat bone metastasis in many countries. Efforts to get these oral agents approved in the U.S to provide patients with more choices should be considered. While S0307 did not show a difference between the 3 bone-targeted agents, the combined analysis of prior studies comparing bisphosphonates to placebo/control in early stage breast cancer support the conclusion that bisphosphonates can reduce breast cancer recurrences and death in postmenopausal women. S0307 shows that there is no superior agent. Expect more discussion about the role of bisphosphonates in early stage breast cancer following the full publication of the meta-analysis paper in the journal Lancet in the near future.
Abstract 504 (M Gnant et al) – Denosumab (Xgeva) to reduce fractures for women taking aromatase inhibitors
In addition to the bisphosphonates, RANK ligand inhibitors are a second class of bone-targeted agents. Denosumab (Xgeva) is a RANK ligand inhibitor approved for treatment of osteoporosis and bone metastasis. The ABCSG-18 study evaluated the impact on the bone of every 6 month subcutaneous injections of densosumab versus placebo in postmenopausal breast cancer patients receiving the aromatase inhibitors anastrozole (Arimidex) or letrozole (Femara) for early stage breast cancer. Because aromatase inhibitors are known to accelerate bone breakdown and increase fractures, the hypothesis was that the addition of denosumab would reduce fractures in this population. Time to first fracture was the primary endpoint. At 6 years, there were 172 fractures in the placebo arm (10.3% of patients), and 92 in the denosumab arm (5.4% of patients). Denosumab therefore reduced fractures by 50%. Bone mineral density was also increased in the group receiving denosumab. Interestingly, the same benefit was seen for women who had had normal bone density at the time they enrolled in the study as for women who already had decreased bone mineral density, meaning that it is important to monitor bone loss for all patients treated with aromatase inhibitors. There was very little difference in toxicity between the denosumab and placebo arms, with no cases of osteonecrosis of the jaw. The conclusion of this study is that fractures are common in postemenopausal breast cancer patients on aromatase inhibitor therapy, and that we have interventions with low toxicity that can reduce fracture risk. Could denosumab also reduce breast cancer recurrences like the bisphosphonates (as discussed above)? We have no data yet. ABCSG18 will eventually evaluate this when enough breast cancer events have occurred, althoiugh it will not likely have the statistical power to make definitive conclusions. The ongoing D-CARE trial is large Phase III trial in early stage breast cancer evaluating denosumab versus placebo in reducing breast cancer recurrences.
Abstract 505 (L Gianni et al) – Preoperative HER2-targeted therapy with pertuzumab (Perjeta)
Pertuzumab (Perjeta) was first approved in treating HER2+ metastatic breast cancer, and results previously reported from the NeoSphere clinical trial resulted in the recent FDA approval of pertuzumab in the preoperative (neoadjuvant) setting. The phase II NeoSphere trial evaluated preoperative drug combinations in HER2+ breast cancer. It previously showed that patients who received 2 HER2-targeted antibodies, trastuzumab (Herceptin) and pertuzumab (Perjeta), in combination with the chemotherapy agent docetaxel (Taxotere) before surgery had a higher rate of complete elimination of all invasive cancer in the breast and lymph nodes at the time of surgery (pathologic complete response, also called a pCR), when compared to docetaxel given with either HER2 antibody alone, or the 2 HER2 antibodies given together but without chemotherapy. But higher pCR rates do not necessarily mean that there will ultimately be less recurrences or deaths, which are the most important outcomes for patients. The current ASCO presentation of NeoSphere showed 5 year follow-up of this trial, with a focus on breast cancer recurrences. All patients received identical FEC chemotherapy (5-flurouracil, epirubicin, and cyclophosphamide) and a full year of trastuzumab following surgery. Since this was a trial focused on the surgery results as the primary endpoint, it was not well powered to evaluate recurrences. The recurrence data shown at ASCO suggested superior long-term outcomes for the group that received both of the HER2 antibodies along with chemotherapy before surgery. The improvement was greater for tumors that were estrogen receptor (ER) negative. Cardiac events were higher when all 3 drugs were given together, although serious heart effects were low, and all but one of the declines in cardiac function have recovered. The conclusion was that the recurrence results are in line with the results of the primary endpoint, pCR, and suggest a benefit of adding pertuzumab to trastuzumab and docetaxel in the neoadjuvant setting. The NeoSphere trial findings are not strong enough to support adding pertuzumab in all early stage HER2+ breast cancer patients. The APHINITY trial is an ongoing phase III trial in early stage breast cancer patients evaluating the benefit of adding pertuzumab to chemotherapy plus trastuzumab following surgery (the current standard). This is the definitive trial that we will need to see to determine whether the addition of pertuzumab results in improved outcomes in HER2+, early stage breast cancer. We hope to see the results of the APHINITY trial within a year.
Abstract 506 (N Harbeck et al) – Preoperative HER2-targeted therapy with ado-trastuzumab emtansine (T-DM1, Kadcyla)
T-DM1 (Kadcycla) is an interesting drug that links the HER-2 antibody trastuzumab (Herceptin) with a toxic chemotherapy drug, delivering the chemo directly inside HER2+ breast cancer cells instead of exposing the whole body to the toxic effects of chemotherapy. It is already approved in treating metastatic HER2+ breast cancer. The ADAPT trial is a preoperative trial, with different drug combinations tested based on the tumor subtype. Results from the HER2+/ER+ breast cancer subset were presented at ASCO. In this group of patients, the study evaluated the antibody-drug conjugate T-DM1 (with or without simultaneous endocrine therapy) versus trastuzumab plus endocrine therapy, all given for 12 weeks prior to surgery. None of the patients received chemotherapy before surgery. The endpoint was pathologic complete response (no invasive disease in the breast or lymph nodes at the time of surgery, pCR). The combined T-DM1/endocrine therapy arm had a 46% pCR rate, the T-DM1 alone arm had a pCR rate of 41%, and the trastuzumab/endocrine arm had a pCR rate of only 7%. The patient numbers are too small to say that endocrine therapy should be added to TDM-1, but clearly the response rate for T-DM1 was impressive and far superior to trastuzumab alone. Adding endocrine therapy to T-DM1 seemed to have more possible benefit in premenopausal patients, although the number of patients in each category was small and this should be viewed as a preliminary finding. More patients in the T-DM1 arms had elevations in their liver tests, decreases in their platelet counts, and infections, although these were rarely serious and all patients recovered. Take home point: The high pCR rate for T-DM1 in this study, with little toxicity compared to what we would expect from combined chemotherapy and trastuzumab, is very promising and needs to be tested in larger, more definitive trials. These studies are already ongoing. It’s possible that we will be able to define a chemotherapy-free regimen for early stage HER-2+ breast cancer patients that will prove to be at least as effective and less toxic than our current regimens.
Abstract 508 (A Chan et al)
Neratinib is another HER2-targeted drug that is not yet approved in any setting. It is taken by mouth, and is a tyrosine kinase inhibitor of not just HER2, but also other members of the HER family including HER1 and HER4. The Phase III ExteNET study enrolled 2,821 patients with HER2+ early stage breast cancer who had already received chemotherapy and a full year of trastuzumab to receive an additional year of neratinib versus placebo. The purpose of the study was to investigate whether neratinib can further reduce recurrences following standard chemotherapy and trastuzumab. Of note, the HERA study failed to demonstrate any benefit from extending adjuvant therapy with trastuzumab from one to two years. The primary endpoint of ExteNET was invasive disease free survival (being alive without an invasive breast cancer recurrence, iDFS). With two years of follow-up, the iDFS was 94% for the neratinib arm versus 92% for the placebo arm, and the difference was statistically significant. There was a possible greater benefit in the ER+ subset. A major and common toxicity of neratinib is diarrhea, with 40% of patients receiving neratinib experiencing serious (grade 3) diarrhea, and requiring loperamide (imodium). In the discussion and question and answer sessions, the two-year follow-up time was felt to be too short for conclusions about the utility of adding this agent following standard adjuvant HER2 therapy. Additionally the significant diarrhea was felt to be a major limitation of this drug, especially for such a small difference in recurrences. Nonetheless, there are plans to submit this drug to the FDA in the near future. Neratinib continues to be explored for other indications within HER2-positive breast cancer.
Feeling confused by trial terminology? PFS = progression free survival; OS = overall survival; RR = response rate; ORR = overall RR. #ASCO15
— Merry J Markham, MD (@DrMarkham) June 1, 2015
Dr. Matt Katz presented on disease specific hashtags for online communication about cancer care – view the poster here: http://www.slideshare.net/subatomicdoc/disease-specific-hashtags-for-communication-about-cancer-care-48866106
There are a tremendous amount of resources from the meeting that ASCO has made available. All of the Abstracts can be found by searching here: http://abstracts.asco.org/156/IndexView_156.html
A comprehensive Educational Book, edited by Dr. Don Dizon can be found here: https://am.asco.org/sites/am.asco.org/files/Ed_Book_2015.PDF includes an interesting section on individualizing the approach to the older woman with breast cancer (begins on page 47).
View Dr. Ginsburg’s video on Global Cancer Control Updates from ASCO
A highlight for many of us attending national meetings is the opportunity to catch up with colleagues scattered across the country (and in some cases, across the world) that we only see once a year. ASCO hosted a tweetup – click the pics to see the associated tweets:
— Julie Gralow (@jrgralow) May 30, 2015
— Dr. Deanna Attai (@DrAttai) May 30, 2015
Finally, it wouldn’t be a #BCSM post without ending with, you guessed it…
— Dr. Deanna Attai (@DrAttai) June 2, 2015
I couldn’t resist!