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new immunotherapy

The oncology world appears to be on the verge of revolution, not simply evolution. The notion of immunotherapy as a means of cancer therapy has been one of the oncological “holy grails” for years. Major developments have been seen in melanoma first with ipilimumab which targets CTLA-4 and augments the immune attack on cancer. The inhibitors against PD1 and PDl1 have a different mechanism blocking immune tolerance to cancer, or as I like to think of it, removing the cancer camouflage, exposing it to attack. The Austin and other institutions are now in the throes of Phase I-III studies testing these new agents. This was as a result of data such as http://www.nejm.org/doi/full/10.1056/NEJMoa1200690 where an efficacy signal was seen for the first time.

clinical trials

For those who are interested we have a whole host of studies in lung cancer at the Austin hospital testing agents targeting EGFR, ALK and PD1/PDL1. The breast cancer portfolio was a wee bit quiet  for a year but this is expanding including studies in triple negative breast cancer. Phase I studies run by A/P Hui Gan include a novel PARP inhibitor (attractive in breast and ovarian cancer  partic in the BRCA +ve patients).

We are very collaborative in Melbourne and I work closely with colleagues at Peter Mac , Royal Melbourne Hospital (only to name a few centres) to give patients the option to participate in studies that suit their particular circumstances better. This is often under the auspices of Cancer Trials Australia (see introduction).  We strongly encourage patients to consider trials. Ultimately as their clinician, I want them to personally  benefit from such participation. It is  true that altruism is maybe  an important part of developing  new and better treatments and improved outcomes in cancer medicine, and in health in general. SW Aug 2014

SOFT/TEXT ASCO presentation/publication in NEJM

This was a combination of 2  trials (SOFT/TEXT) for a total of  4690 premenopausal  pts with hormone drive early breast ca (ER+)

All were treated  with ovarian suppression (injections or ovarian surgery /radiation)  for 5 yrs and either tamoxifen or exemestane. Exemestane is an aromatase inhibitor  (AI)(like anastrozole and letrozole) which is superior to tamoxifen in the ppost menopausal setting. Thus, the SOFT/TEXT study aimed to emulate these results in premenopausal patients.

Overall 5yr DFS (prim endpt) was 91.1% for exe vs 87.3% tam. So there was a 4% improvement in freedom from breast cancer recurrence (helping an extra 1/25 patients). Some criticisms or concerns would include the lack of long  term followup and assessment of implications for bone  thinning (osteoporosis) and cardiovascular disease. The AIs can be challenging with higher rates of joint aches, mood disturbance and libido issues.

My sense is that this may suit the right premenopausal patient with higher risk disease who wants to maximise theie therapeutic gain and has maybe through chemotherapy not found the hormonal disruption troubling in the leadup to this discussion and consideration. A quirk of the PBS is that exemestane can only be used after prior TAM for 2-3 years but I don’ t regard its action as  having a therapeutic advantage over the other AIs which are PBS listed ‘up front’. http://www.nejm.org/doi/full/10.1056/NEJMoa1404037

ZOOM 1 study 2013

At EBCC , the ZOOM data was highlighted http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70297-3/fulltext.  For years clinicians have remained concerned that we are overusing anti-resorptive agents in advanced breast cancer with bone metastases. This data showed no detriment in outcome with a reduction in the use of zoledronic acid (ZA) to 12 weekly in year 2 of treatment. At the least, this new approach will improve patient convenience , and may impact somewhat on the incidence of  osteonecrosis of the jaw (BONJ).

It is speculative as to how to apply this new data to  denosumab, which  was not assessed in this study. Nevertheless, it is intriguing and not unreasonable to think that a similar result would be seen with denosumab, particularly as it is slightly more effective than ZA in the first instance.

EBCC Glasgow 2014 Bisphosphonate debate

one of the  highlights was the debate between Robert Coleman (Sheffield UK) who has led this area and Gabriel Hortobagyi (MD Anderson, Tx,US). Robert reiterated data presented at SABCS 2013 , a metaanalysis of 36 studies and > 18000 patients showing an  reduction in the development of bone metastases and a 3% improvement in overall mortality for post menopausal women with ER+ve breast cancers.

Hortobagyi’s concerns were statistical, but relevant. There was tremendous heterogeneity amongst the studies, none of the studies met their individual primary endpoint (let alone the metaanalysis), the study outcome  was inversely proportional to size, and there was no interaction between schedule type of agent.

Certainly on the basis of no real data Coleman was recommending a 6 monthly schedule of zoledronic acid as per the Austrian study 12 and also the later part of the schedule of ZA in Coleman’s own AZURE study.

(SW) This is contentious and no bisphosphonate is TGA approved for this indication, nor funded on the PBS. Its use would  need to be case by case and i think logically, related to the absolute  risk of relapse of the individual patient. The toxicities of osteonecrosis of the jaw (albeit low 1-2%) need to be considered also.

carboplatin increases responses in NAC in women with triple negative breast cancer

it seems clear through multiple studies that carboplatin improves the pCR (pathological complete response rate) in women having NAC (neoadjuvant or preoperative chemotherapy) in the setting of triple negative breast cancer.

It clearly adds toxicity through low white cells, and it remains unclear whether the benefit increases the chance of cure. The jury is still out but certainly could be considered in circumstances where the cancer is not initally responding well to standard therapy.

Bisphosphonates as adjuvant therapy

evidence from San Antonio Breast  Cancer Symposium supporting a small but real advantage for bisphosphonates in  improving outcome for post menopausal women with hormone-driven breast cancer. This probably is through reduction in the development of bone metastases.

It is unclear whether potent intermittent intravenous zoledronic acid is to be preferred over potentially weaker oral agents commonly used in osteoporosis such as risedronate and alendronate.

BCNA forum december

BCNA will be hosting a community forum for women, their family members and friends in Melbourne on 5 December 2013. We hope you can promote this free event to women in your care through your regular communications or by printing and displaying the promotional poster<http://cl.exct.net/?qs=2423273aea03ec5a05f7e77c79b6f20eee9c199569bb553f246d30cd6a6d1929>. Health professionals are also welcome to attend.

 

The forum features presentations by breast cancer clinicians on clinical and psychosocial topics, including:

 

*   Dr Richard de Boer on the latest in treatment and care

*   Jane Fletcher on ways to improve emotional and physical wellbeing

*   Raelene Boyle, Olympian and breast cancer survivor.

 

Women, partners, family members and friends will benefit from meeting others living with breast cancer and hearing about local breast cancer services and supports available.

 

Forum details:

 

Living well beyond breast cancer

 

Thursday 5 December, 10.00 am – 3.00 pm

 

Lunch: Refreshments and a light lunch will be served.

 

Venue: The Event Centre at Flemington Racecourse, Skyline Room (Level 3), 448 Epsom Rd, Flemington, Vic.

 

Cost: This event is free. Participants are welcome to bring along a partner, family member or friend.

 

Registration: Register online at www.bcna.org.au/events/forums<http://cl.exct.net/?qs=2423273aea03ec5ae214d904aa486b7caff67615c171c163eac44d5021280f63> or phone 1800 500 258.

Day 1 – world lung

  • EGFR inhibitors can have modest efficacy in uncommon eEGFR mutations but not in T790m de novo mutations and exon 20 insertions (analysis of LUX studied with afatinib
  • 4% risk of dangerous interstitial lung disease with EGFR TKIs in Japanese populations with a mortality of 1.5% . Note this risk incidence does not apply to Caucasian population

LUX 4 afatinib post progression in EGFR mutated disease

the study

http://jco.ascopubs.org/cgi/content/short/31/27/3335?rss=1  showed  a small number of partial responses (good tumour shrinkage) and an average disease control time (PFS ) of over four months. Not startling..the overall survival was good (19 months average) but this reflects (more likely ) the better biology of EGFR m+ adenocarcinoma of  the lung