Saturday, June 11, 2016

The Days of ASCO 16: Ovarian Cancer Research

This post will concentrate on information I learned during the gynecologic cancer sessions which focused on ovarian cancer. A future blog post will discuss research presented on other gynecologic cancers.

Intraperitoneal Chemotherapy for Ovarian Cancer: Trials and Tribulations
Presenters: Drs. Walker, Gourley, Mackay 
A discussion of GOG252 ( phase III trial) that compared IP and IV chemotherapy. All arms received Bevacizumab.
  • Arm 1: intravenous carboplatin AUC (area under the curve) 6/intravenous weekly paclitaxel at 80 mg/m2
  • Arm 2: intraperitoneal carboplatin AUC 6/intravenous weekly paclitaxel at 80 mg/m2
  • Arm 3: intravenous paclitaxel at 135 mg/m2 on day 1/intraperitoneal cisplatin at 75 mg/m2 on day 2/intraperitoneal paclitaxel at 60 mg/m2 on day 8. (Control)
This ASCO POST article  on this session also discusses the trial.

Progession Free Survival (PFS) for all arms was similar
IP cisplatin arm had increased blood pressure with Bevacizumab
16% of the IP patients moved into the IV arm which may have influenced results
Neurotoxicity side effect in all arms were equal. All are lower than in GOG 172.
Questions asked regarding the  GOG 252 results:
    Did the dose dense paclitaxel in control make the control arm better than the control arms in the  other studies? 
    Did the addition of Bevacizumab negate the previous positive IP results? 
    Did the surveillance with CT every 6 months decrease PFS results?

Other studies ( GOG 104,114,172) showed longer PFS using IP compared to  IV 
The subgroup of BRCA1/2 patients could benefit from IP

"There are still unresolved issues" regarding the use of IP chem
No evidence for combining IP/IV with Bevacizumab
No data so therefore no role of HIPEC ( hyperthermic interperitoneal chemotherapy) to treat ovarian cancer outside of clinical trial. 
Need to understand the microenvironment and biology of  OC
Would use of IP chemotherapy benefit subgroups of patients based on histologic or molecular profiles or platinum sensitivity? 

Divide and Conquer: Epithelial OC Beyond BRCA
Kristeleit, Kohn , Goodfellow 

This session discussed genes and pathways that influence the development of ovarian cancer. In addition to germline BRCA 1/2  mutations you can also find somatic BRCA 1/2 mutations, BRCA1 methylation, EMSY amplification, TP53, mutation, tumour suppressors RB1, NF1, RAD51B and PTEN ( which can lead to chemo resistance) and overexpression of MDR1.

Some clinical trials are also looking at Wee1 inhibition ( phase II), Hypoxia, combining parp inhibitors and immunotherapy, and PD1, PDL1 immunotherapy. 

Symptom Management for Patients with Gynecologic Cancers 
Le, McCormack , Mayer  
Dr Le spoke about the impact of menopause symptoms ( hot flashes, genitourinary ) after surgery. She recommended asking patients about what menopausal symptoms they were experiencing, assess the risk of hormone therapy and refer to  gynecologist/PCP for hormonal or non-hormonal treatment. 

Survivorship Care Plans
Dr Mayer presented background information about the quality of life issues of women diagnosed with ovarian cancer. This slide shows the informational needs of ovarian cancer survivors ( Papadakos, 2012). Younger women had greater needs than older women. 

She concluded that women with gynecologic cancers can experience a number of long terms and late side effects, they have unmet needs especially fear of recurrence ,  patient reported outcomes can help identify the issues and survivorship care plans can help address those needs. 

Oral Abstracts- Ovarian Cancer

5501- Overall survival (OS) in patients (pts) with platinum-sensitive relapsed serous ovarian cancer (PSR SOC) receiving olaparib maintenance monotherapy
Patients receiving maintenance olaparib after responding to platinum therapy had an overall survival advantage. Patients with a BRCA mutation and platinum sensitive relapsed serous ovarian cancer showed a significant progression free survival benefit. Germline and somatic BRCA mutation gave the same results. 


5502 Hormonal maintenance therapy for women with low grade serous carcinoma of the ovary or peritoneum Low grade ovarian cancer is more platinum resistant than high grade ovarian cancer. Women with stage II-IV low grade ovarian cancer who received hormonal maintenance chemotherapy following primary treatment had a statistically significant improvement in progression free survival compared with women who were under surveillance . 


LBA5503 OV21/PETROC: A randomized Gynecologic Cancer Intergroup (GCIG) phase II study of intraperitoneal (IP) versus intravenous (IV) chemotherapy following neoadjuvant chemotherapy and optimal debulking surgery in epithelial ovarian cancer (EOC)After 3-4 courses of IV platinum chemotherapy followed by optimal debulking surgery women were optimized to 1) IV carbo/taxol , 2) IP cisplatin / IV taxol or 3) IV taxol/ IP carboplatinum.  The IP carboplatin based regimen, post neoadjuvant chemotherapy and debulking surgery, was tolerated and a lower number of women showed progression at 9 months compared to IV therapy. 


5504 Multicenter phase II study of intraperitoneal carboplatin plus intravenous dose-dense paclitaxel in patients with suboptimally debulked epithelial ovarian or primary peritoneal carcinoma Prospective study of stage II-IV OC. Chemotherapy with dose dense Placitaxel / Cisplatin  is safe and effective for suboptimal residual ovarian patients.


5505 The MITO8 phase III international multicenter randomized study testing the effect on survival of prolonging platinum-free interval (PFI) in patients with ovarian cancer (OC) recurring between 6 and 12 months after previous platinum-based chemotherapy: A collaboration of MITO, MANGO, AGO, BGOG, ENGOT, and GCIG  This study showed that  prolonging the platinum-free interval by using a non platinum based chemotherapy  does not improve and even worsens efficacy outcomes in patients with partially platinum sensitive recurrent ovarian cancer . 


5507 Performance characteristics and stage distribution of invasive epithelial ovarian/tubal/peritoneal cancers in UKCTOCS This study was first discussed at ASCO 2015 and this abstract presented a further analysis. Patients were randomized to either the Multi modal (MM) Risk of Ovarian Cancer Algorithm (ROCA) arm or ultrasound (USS)  for screening. Sensitivity of the MM was 86% with 4 operations per invasive cancer detected. Sensitivity of the USS was 63 % with 17 operations per invasive cancer detected.


 5508 Baseline quality of life (QOL) as a predictor of stopping chemotherapy early, and of overall survival, in platinum-resistant/refractory ovarian cancer (PRROC): The GCIG symptom benefit study (SBS) This Symptom Benefit study showed that Global Health status, Physical function,  Role Function and Abdominal/ GI symptoms were independent predictors for overall survival were significantly associated with stopping chemotherapy early. The worse symptoms the shorter survival. Assessment could help identify patients who may not benefit from palliative chemotherapy. 

Clinical Sciences Session: Leveraging the Immuno-molecular Landscape of Gynecologic Cancers - OVARIAN CANCER

5510 Kurian This study included over 95,000 women with ovarian cancer were tested using the Myriad 25 gene hereditary panel test . Personal histories were also taken. 

Most of the women had BRCA1/2 mutations.  ATM ( a mutation associated with breast cancer)  was seen for the first time . 

5511 Tanyi Mesothelin is a tumor associated antigen in ovarian cancer. This immunotherapy study was Phase 1 and included 6 women with recurrence ovarian cancer . Each women received an intravenous infusion of autologous T cells transduced to express a chimeric antigen receptor directed against mesothelin (CART-meso). The infusion was found to be safe. 


Education Session : Neoadjuvant Chemotherapy : Location , Location Location                    Leary and Chi  

There is a risk of progression while on neoadjuvant chemotherapy (NACT). There may also be a risk of driving chemo resistance on NACT. Previous studies showed improved survival but there was no quality control of the surgical aspect of the trials. How much disease remained after surgery? Ultimately it is the clinicians decision whether or not to use neoadjuvant chemotherapy. 

Here is an SGO video on ovarian cancer research at #ASCO16 on ovarian cancer. Presenter is Dr Shannon Westin, MD Anderson.

Every Day is a Blessing! 

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