Some Thoughts on Quality of Life , Patient Reported Outcomes and Clinical Trials

A few days ago @DrYukselUrun shared on X the ORR ( objective response Rate) and CRR (Complete Response Rate and OS (overall survival) for the  Phase 3 CLEAR trial ( combo of Lenvatinib and Pembrolizumab in advanced renal cell carcinoma).  

 In response,  @StrijbosMichiel posted "Most impressive results from the CLEAR trial: the percentage of patients that have to endure grade 3-4 toxicities....82.3% in the 2021 NEJM publication. Yes you live longer....but at a very very hefty price. "  

Deb Maskens (@DebMaskens) a kidney cancer patient advocate posted: "Please do not post Efficacy numbers without posting what is equally important to patients: Quality of Life! Not just how long we live, but HOW we live. TY" (my emphasis)

What followed was an interesting discussion about QOL when testing new treatments and how they are measured and reported.  What is tolerable for one patient may not be tolerable for another. The fatigue one patient experiences may mean they feel tired for another it may mean they are unable to move out of bed or stand to take a shower.  Trials will report the AE's (Adverse Effects) as recorded by the clinicians and investigators or another person involved in the study. Occasionally patient reported outcomes (PROs) are included as part of the trial.  At oncology meetings there is usually a slide reporting the % of patients enrolled in the trial who experienced AE's from grades 1-4, but the focus when presenting the data is usually on the ORR, PFS or OS.  

It is important that patient reported outcomes become a standard part of the clinical trial process in oncology. The FDA issues a Draft Guidance on Core Patient-Reported Outcomes (PRO) in Cancer Clinical Trials in June 2021.  The guidance includes various tools that can be used to measure patient reported outcomes in the areas of disease related symptoms, systemic adverse events, overall side effect measures , physical function and role functions. It also shows the frequency at which those measures shoe be recorded. The FDA considers PRO's( Clinical Outcome Assessments)  as part of the COA's of a trial (https://www.fda.gov/science-research/focus-areas-regulatory-science-report/focus-area-patient-reported-outcomes-and-other-clinical-outcome-assessments). 

I've been thinking about the tools to measure PROs. There is a specific one for ovarian cancer called FACT-O (Functional Assessment of Cancer Therapy – Ovarian (FACT-O). The Assessment covers physical well-being, social/family well-being, emotional well-Being, functional well-being. Patients are asked to respond to statements that have been found to be important by others diagnosed with cancer with one of 5 responses from "not at all" to "very much". What about those issues not listed in the items others found important. There are vision issues with some anti-body drug conjugates now used to treat ovarian cancer but vision is not listed. Others including myself have had dental/ mouth issues during treatment which affect QOL and may fall under other categories but dental issues are not specifically mentioned. There is no space on the questionnaire to enter concerns that are not listed.  I understand it is difficult to capture all of the patient experience in a single questionnaire. 

At the recent ASCO 24 Annual Meeting there were multiple sessions and a keynote speech about artificial intelligence (AI). Can we use AI to read text from patients for example in a treatment diary or in an open ended question on a QOL form? Could those open ended responses be read by the study team in real time - not just for study analysis- so they can be responded to quickly?  How difficult would it be to implement that analysis in all clinical trials in ovarian cancer and other cancers going forward? I don't have the an answer for these questions but I am sure their are other experts who could provide some information. I also would like to see the conclusion slide of each presentation at oncology meetings include those QOL measurements and not a simple statement that there are " no new safety signals" . What were the old signals? 

We have work ahead but patient advocates, the FDA, Pharmaceutical companies and clinicians can work together to insure the patient experience and voice is recorded and used when considering approving treatments.

I'd love to hear from those in AI about the feasibility of implementing AI analyzed textual PROs or those with other ideas on how we can advocate for a greater use of PROs.

Dee

Every Day is a Blessing !

Ovarian Cancer Research at the Cancer Survivorship Research Conference- Part 4

The focus of this conference was survivorship but I did find two posters that dealt with ovarian cancer survivorship in particular.

Impact of Chemotherapy-Induced Neuropathy on Quality of Life Among Ovarian Cancer Survivors: Results from the Population-Based Profiles Registry

This study was done in the Netherlands.  I had the opportunity to speak directly to Lonneke van de Poll-Franse, PhD one of the researchers . She told me that the number of women diagnosed with ovarian cancer in the Netherlands was 800 just slightly more than the number diagnosed each year in New Jersey. I thanked her for doing research on a subject so important to ovarian cancer survivors. The conclusion of the study as reported on the poster was that “Neuropathy symptoms were experienced by 51% of women with ovarian cancer who receive chemotherapy even up to 12 years after the end of treatment and seriously affect their health related quality of life.”

The second study, done in the United States is an ongoing GOG study. The GOG group is now part of NRG Oncology.

Baseline Characteristics of Ovarian Cancer Survivors Enrolled in a Lifestyle Intervention Trial: Lives Study

The LIVES study  is recruiting women with stage II –IV ovarian cancer from 230 GOG clinics. The study has recruited 20% of its goal . Women were randomized to the lifestyle intervention group or the control group.  In the lifestyle group the womenwill receive information about healthy lifestyle and nutrition and is delivered via the internet using a special interactive platform. More information can be found at http://ovarianlives.org/

Dee

Every Day is a Blessing!

ASCO from a Distance Part II

I continue to work my way through the ASCO Annual meeting abstracts and news reports. These might be of interest to my readers.

A randomized multicenter phase III study comparing weekly versus every 3 weeks carboplatin (C) plus paclitaxel (P) in patients with advanced ovarian cancer (AOC): Multicenter Italian Trials in Ovarian Cancer (MITO-7) -- European Network of Gynaecological Oncological Trial Groups (ENGOT-ov-10) and Gynecologic Cancer Intergroup (GCIG) trial"
The standard chemotherapy for ovarian cancer is carboplatin(C) and paclitaxel(P) every three weeks. This study compared that standard treatment plan with weekly C & P at lower doses. There were 822 women in the study. The study concluded " Compared to standard CP every 3 weeks, weekly CP did not demonstrate a significant benefit in PFS, but was associated with better QoL and toxicity. " (QoL - quality of life PFS Progression free survival)
I had the standard 3 week C&P when I was first diagnosed. If the weekly treatment were to be offered to me today I think I would choose the extra infusion visits for the better quality of life, less fatigue, neutropenia, low platelets etc.

Phase II study of trabectedin in pretreated patients with recurrent epithelial ovarian cancer (REOC). 
This non-randomized study of 16 women examined the use of single agent Trabectedin in women with recurrent ovarian cancer. Trabectedin is also known as Yondelis and is an agent derived from the sea squirt. It works by cleaving DNA of the tumor cells and cause them to die. It is approved in Europe for soft tissue tumors in platinum sensitive women. Women were given dexamethasone prior to the Trabectedin to reduce toxicity. Although there were no complete responses there were partial responses and stable disease reported. The conclusion was:  "Trabectedin 1.1mg/m2 given as a 3-hour i.v. infusion every 3 weeks was well tolerated and has confirmed a very interesting antitumor activity in this heavily pretreated population and it seems also to be a very tolerable regimen. The co-treatment with dexamethasone improves the safety of Trabectedin by reducing drug-induced myelosuppression and hepatotoxicity. Trabectedin has a manageable toxicity profile, and can be safely administered thanks to its secure action profile also in patients with no other viable therapeutic options.  " Trabectedin was tested with Doxil but was rejected by the FDA due to liver toxicity. I wonder if other drugs combined with Trabectedin or the use of dexamethosone would help move this agent down the  path to approval for recurrent ovarian cancer. 

Here is some interesting research on the psychosocial issues facinc adult vs childhood survivors. 

Psychosocial health in survivors of adult versus childhood cancer. 
This study compared depression, anxiety, post traumatic stress disorder etc in adult and child cancer survivors. They concluded "Survivors of adult onset cancer face a significantly higher amount of psychologic distress, particularly depressive and somatic symptoms, compared to their childhood counterparts and age-expected norms. Analyses are ongoing to evaluate other demographic, disease, and treatment related risk factors that may contribute to this age-related phenomenon in order to develop interventions."I wonder if they will look at the fact that most adults have financial/ work issues to increase their stress.

Dee
Every Day is a Blessing! 

ASCO - Patient and Survivor Care

Part four in my ASCO report. 

I spent time chatting with researchers and reading many posters related to patient survivorship issues at ASCO. It pleased me that researchers were spending time looking at quality of life, anxiety , sexual function , support efforts, hope, obesity and improving side effects. 

Obesity

The researchers looked at obesity and survival in ovarian cancer patients. They compared 130 obese vs 240 non-obese women with the disease. The time to recurrence was identical at 15 months in both groups. They concluded that obesity does not impact time to recurrence. (Abstract 5049)

Quality of Life/ Hope 

This longitudinal study by researchers from the Cancer Treatment Centers of America studied whether changes in quality of life could predict survival in ovarian cancer patients treated in an integrated model. There were 137 patients in the study and included newly diagnosed and those with recurrences. Quality of Life questionnaires were completed at initial visits and at 3 months of treatment. Preliminary evidence showed that patients with improved quality of life at three months had significantly longer survival. (Abstract 5049)

Researchers from Germany used a questionnaire to study sexual function in ovarian cancer patients. The study included over 700 women. Half of the women reported they were not sexually active. Results showed that sexual activity was impaired in women with ovarian cancer but that it did not impact their quality of life. The researchers concluded that a shift in priorities regarding anxiety due to cancer survival may have impacted the results.(Abstract 5051)

A longitudinal study by MD Anderson researchers studied ovarian cancer patients at MD Anderson, an academic cancer center and a community hospital. Results showed that underserved patients in the community hospital setting had poorer quality of life and that the future depended on “luck” or “others”. than those at the cancer centers. ( Abstract 9134) This is the poster of the work Dr L Ranondetta described at the Grand Rounds at St Peters University Hospital in May.

The Lance Armstrong Foundation researchers fielded a LiveSTRONG Survey for People Affected by Cancer. The survey looked at post treatment concerns and treatment summaries. Results showed that only one third of the patients received a treamtnet summary. Those patients that did receive a summary had a variety of positive outcomes. ( Abstract 9136)

Therapy management/ Anxiety

A German Study surveyed 676 ovarian cancer patients  regarding their expectations and needs about their therapy and doctor /patient communications. They found there is a high need of patients to discuss all details of treatment options and clinical management. the three most important aspects were “More time for discussion”, “therapy should not lead to hair loss” ad “therapy should be more effective”. 

(5044)

Side Effects/ Hair loss

This prospective study of chemo induced hair loss with and without scalp cooling was done by researchers in Canada. Researchers studied 130+ women with and without a scalp cooling device.  The study used  a survey and photos were taken before treatment,at 3 cycles and at the end of treatment. The result showed 49% of women who used the scalp cooling described their  “Success” as none or little hair loss . While 4% of women who did not use the scalp cooling had “Success”.   Hair stylists reported “success at 34% for those using the cooling device (Abstract 9138)

Dee

Every Day is a Blessing!