[NICE Guidline] Isatuximab with pomalidomide and dexamethasone for treating relapsed and refractory multiple myeloma

NICE|Isatuximab with pomalidomide and dexamethasone for treating relapsed and refractory multiple myeloma | Technology appraisal guidance [TA658]| Published date: 18 November 2020

Evidence-based recommendations on isatuximab (Sarclisa) with pomalidomide and dexamethasone for treating relapsed and refractory multiple myeloma in adults.

Further details are available from NICE

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NICE

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NIHR: First-line chemotherapy for ovarian cancer given once every three weeks may preserve quality of life

NIHR | November 2020| First-line chemotherapy for ovarian cancer given once every three weeks may preserve quality of life

NIHR’s latest evidence feature focuses on research that studied the chemotherapy treatment women with a new diagnosis of ovarian cancer receive, this type of cancer is usually treated every three weeks with chemotherapy containing the medicines carboplatin and paclitaxel. Although a recent Japanese studied reported better outcomes without reducing quality of life for weekly chemotherapy, the researchers behind this study found that patients who received weekly paclitaxel had poorer quality of life during treatment. They were also more likely to have nerve damage that lasted up to 18 months.

Taken together with the lack of progression-free survival benefit, their findings do not support routine use of weekly paclitaxel-containing regimens in the management of newly diagnosed ovarian cancer.

What’s new?

1438 women with ovarian cancer were asked about their quality of life at regular intervals for up to five years after starting treatment. They completed written questionnaires on factors such as emotional well-being, fatigue and nerve pain.

Nine months after patients entered the trial, the researchers found:

  • Patient well-being fell during chemotherapy but then improved over the following months regardless of which treatment was given
  • When researchers looked at well-being scores during and after treatment, those on weekly treatment experienced lower quality of life compared to those receiving treatment every three weeks
  • Nerve damage caused by paclitaxel was worse in the weekly treatment arms and persisted for longer. It started later than in women receiving chemotherapy every three weeks
  • Patients having weekly treatment reported slightly increased levels of fatigue compared to those treated every three weeks but this was not significant.

Although survival was similar for patients on all treatment plans, well-being data shows a different story. The study suggested weekly schedules were harder for patients to tolerate and caused long-lasting toxicity compared to less frequent chemotherapy.

The researchers believe that three-weekly chemotherapy should remain the standard of care for most newly-diagnosed ovarian cancer patients.

It is not known why paclitaxel causes nerve damage. The researchers in this study believe long-lasting nerve damage and numbness are likely because the total amount of paclitaxel given is higher for people taking weekly treatment (Source: NIHR)

Primary paper:

Blagden, S.P. (2020) et al. Weekly platinum-based chemotherapy versus 3-weekly platinum-based chemotherapy for newly diagnosed ovarian cancer (ICON8): quality-of-life results of a phase 3, randomised, controlled trialThe Lancet Oncology|21|P. 969-977

University of Leeds: ‘First of its kind’ lung cancer trial

University of Leeds | November 2020| ‘First of its kind’ lung cancer trial

Scientists from the UK universities of Leeds, Newcastle, Manchester and Glasgow have been awarded funding of £900,000 by Cancer Research UK; the CONCORDE trial will explore the use of new drugs alongside standard radiotherapy in the hope of improving survival for people with advanced non-small cell lung cancer (NSCLC).

The team of researchers hope that the new drugs will make radiotherapy more effective, increase its ability to eradicate tumour cells and potentially offer new hope to lung cancer patients (Source: University of Leeds)

Full details of the trial are available from the Leeds press release

NICE recommends new chemotherapy-free treatment option for people with untreated chronic lymphocytic leukaemia

NICE | November 2020 | NICE recommends new chemotherapy-free treatment option for people with untreated chronic lymphocytic leukaemia

NICE has recommended a new chemotherapy-free treatment option for people with untreated chronic lymphocytic leukaemia (CLL) in final draft guidance.

The recommendation of venetoclax plus obinutuzumab is set to benefit more than 1,000 people each year. The new fixed 12-month chemotherapy-free treatment will be offered to people with CLL who have not received any prior treatments.

CLL, a type of cancer that affects white blood cells, is the most common of the chronic leukaemias and accounts for around 30% of all leukaemias affecting adults. In England there were 3,157 new cases of CLL in 2017.

Venetoclax plus obinutuzumab will be offered as a first-line treatment to people with CLL, with certain genetic abnormalities (such as a 17p deletion or TP53 mutation). For those without a 17p deletion or TP53 mutation, venetoclax plus obinutuzumab will be offered to those people with untreated CLL for whom fludarabine plus cyclophosphamide and rituximab (FCR) or bendamustine plus rituximab (BR) is unsuitable.

NICE has also recommended venetoclax plus obinutuzumab as a new treatment option via the Cancer Drugs Fund, for people with untreated CLL without a 17p deletion or TP53 mutation for whom FCR or BR is suitable. This is so more evidence can be gathered on its cost effectiveness in this group (Source: NICE).

Full news story is available from NICE

ICR: What are the biggest issues in drug discovery and development?

Institute of Cancer Research | November 2020 | What are the biggest issues in drug discovery and development?

A panel of academic and industry experts have called on the NHS to pay less for drugs used to treat cancer. The summit held last summer by the Institute of Cancer Research (ICR) brought leading organisations from across the academic, charity, pharmaceutical and medical sectors.

The Summer Summit brought together experts from 16 leading academic institutions, charities, stakeholder groups and pharmaceutical companies and calls for a ‘variable pricing’ model based on the benefits they deliver to patients. The peer organistaions that participated in the summit, reached consensus and they identify several measures that will improve the current system of developing drugs, these are some of the solutions proposed to some of the biggest issues in drug discovery and development.

  • Increasing incentives to discover and develop innovative treatments
  • Enabling companies to work together more easily
  • Flexible pricing for new medicines
  • Improving the creation and use of biomarker tests
  • New indicators of effectiveness to speed up clinical trials

The stakeholders at the summit also developed a nine point plan looking at practical recommendations to improve access to new cancer treatment.

The fuull blog post is available from The Institute of Cancer Research

The list of consensus statements is available from The Institute of Cancer Research

See also:

BMJ NHS should vary price it pays for cancer drugs to improve access, say experts

BMJ: Mortality due to cancer treatment delay: systematic review and meta-analysis

BMJ (2020) | Mortality due to cancer treatment delay: systematic review and meta-analysis| 371| m4087

A month long delay in treating cancer is associated with increased mortality for seven types of cancer: bladder, breast, colon, rectum, lung, cervical cancer, and head and neck cancer; delays longer than four weeks are even more detrimental.

For surgery, this is a 6-8% increase in the risk of death for every four week delay. This impact is even more marked for some radiotherapy and systemic indications, with a 9% and 13% increased risk of death for definitive head and neck radiotherapy and adjuvant systemic treatment for colorectal cancer, respectively.

The investigators acknowledge that their results reflect the impact of delay on large and expectedly heterogeneous populations with varying risks of recurrence. Therefore, these estimates are best used at a policy and planning level for modelling, rather than for individual risk prediction (Source: Hanna, et al. 2020).

Abstract

Objective To quantify the association of cancer treatment delay and mortality for each four week increase in delay to inform cancer treatment pathways.

Design Systematic review and meta-analysis.

Data sources Published studies in Medline from 1 January 2000 to 10 April 2020.

Eligibility criteria for selecting studies Curative, neoadjuvant, and adjuvant indications for surgery, systemic treatment, or radiotherapy for cancers of the bladder, breast, colon, rectum, lung, cervix, and head and neck were included. The main outcome measure was the hazard ratio for overall survival for each four week delay for each indication. Delay was measured from diagnosis to first treatment, or from the completion of one treatment to the start of the next. The primary analysis only included high validity studies controlling for major prognostic factors. Hazard ratios were assumed to be log linear in relation to overall survival and were converted to an effect for each four week delay. Pooled effects were estimated using DerSimonian and Laird random effect models.

Results The review included 34 studies for 17 indications (n=1 272 681 patients). No high validity data were found for five of the radiotherapy indications or for cervical cancer surgery. The association between delay and increased mortality was significant (P<0.05) for 13 of 17 indications. Surgery findings were consistent, with a mortality risk for each four week delay of 1.06-1.08 (eg, colectomy 1.06, 95% confidence interval 1.01 to 1.12; breast surgery 1.08, 1.03 to 1.13). Estimates for systemic treatment varied (hazard ratio range 1.01-1.28). Radiotherapy estimates were for radical radiotherapy for head and neck cancer (hazard ratio 1.09, 95% confidence interval 1.05 to 1.14), adjuvant radiotherapy after breast conserving surgery (0.98, 0.88 to 1.09), and cervix cancer adjuvant radiotherapy (1.23, 1.00 to 1.50). A sensitivity analysis of studies that had been excluded because of lack of information on comorbidities or functional status did not change the findings.

Conclusions Cancer treatment delay is a problem in health systems worldwide. The impact of delay on mortality can now be quantified for prioritisation and modelling. Even a four week delay of cancer treatment is associated with increased mortality across surgical, systemic treatment, and radiotherapy indications for seven cancers. Policies focused on minimising system level delays to cancer treatment initiation could improve population level survival outcomes.

Figure1
Visual abstract available from The BMJ, Hanna et al(2020)

Mortality due to cancer treatment delay: systematic review and meta-analysis

NICE: Osimertinib for treating EGFR T790M mutation-positive advanced non-small-cell lung cancer

NICE | October 2020 | Osimertinib for treating EGFR T790M mutation-positive advanced non-small-cell lung cancer

Evidence-based recommendations on osimertinib (Tagrisso) for treating epidermal growth factor receptor (EGFR) T790M mutation-positive locally advanced or metastatic non-small-cell lung cancer (NSCLC) in adults.

Osimertinib for treating EGFR T790M mutation-positive advanced non-small-cell lung cancer

Further information from NICE

NIHR: Breast cancer surgery is safer for older women than has been assumed

NIHR | October 2020 |Breast cancer surgery is safer for older women than has been assumed

Between 2013-2018 over 3000 women aged 70 or over with operable breast cancer were recruited to a NIHR- funded cohort study. The majority (83.4 %) of the women underwent surgery; with researchers tracking their progress for two years. One of the study’s key findings is that no deaths were attributable to surgery for breast cancer. According to the authors of the study, this suggests that surgery for breast cancer in women in this age group is perhaps safer than thought.

This study is part of a wider- Bridging the Age Gaps in Breast Cancer- project which aims to examine the characteristics and outcomes (survival, quality of life and adverse events) of women aged at least 70 years in the UK undergoing surgery for breast cancer.

Researchers found:

  • Fewer than one in five women (19.3%) had an adverse outcome, such as a dangerous blood clot (DVT) or wound pain.
  • a woman’s age predicted what surgery she would receive. The oldest women in the group were twice as likely to have a mastectomy than the youngest women (59.1% vs 29.9%). Younger women were more likely to have breast-conserving surgery, with less breast tissue removed. This may relate to the lack of screening in older women, so cancers tend to be found when they are bigger and women feel a lump.
  • older women were less likely to have lymph glands under the armpit removed (axillary surgery) than younger women (91.4% vs 98.6%). The aim of axillary surgery is to find out if the cancer has spread, and to remove any cancer in the axilla.
  • just 2.8% of the women in this study who had a mastectomy went on to have reconstructive sugery. This compares to one in five (20%) women overall in the UK.
  • quality of life was lower after surgery particularly for those who had more breast tissue removed as in mastectomy.
  • the risk of being unable to carry out some standard day to day tasks was higher after surgery.
Morgan, J. L., George, J., Holmes, G., Martin, C., Reed, M. W., Ward, S., … & Wyld, L. (2020). Breast cancer surgery in older women: outcomes of the Bridging Age Gap in Breast Cancer study. British Journal of Surgery.

Abstract

Background

Breast cancer surgery in older women is variable and sometimes non‐standard owing to concerns about morbidity. Bridging the Age Gap in Breast Cancer is a prospective multicentre cohort study aiming to determine factors influencing treatment selection and outcomes from surgery for older patients with breast cancer.

Methods

Women aged at least 70 years with operable breast cancer were recruited from 57 UK breast units between 2013 and 2018. Associations between patient and tumour characteristics and type of surgery in the breast and axilla were evaluated using univariable and multivariable analyses. Oncological outcomes, adverse events and quality‐of‐life (QoL) outcomes were monitored for 2 years.

Results

Among 3375 women recruited, surgery was performed in 2816 patients, of whom 24 with inadequate data were excluded. Sixty‐two women had bilateral tumours, giving a total of 2854 surgical events. Median age was 76 (range 70–95) years. Breast surgery comprised mastectomy in 1138 and breast‐conserving surgery in 1716 procedures. Axillary surgery comprised axillary lymph node dissection in 575 and sentinel node biopsy in 2203; 76 had no axillary surgery. Age, frailty, dementia and co‐morbidities were predictors of mastectomy. Age, frailty and co‐morbidity were significant predictors of no axillary surgery. The rate of adverse events was moderate, with no 30‐day mortality. Long‐term QoL and functional independence were adversely affected by surgery.

Conclusion

Breast cancer surgery is safe in women aged 70 years or more, with serious adverse events being rare and no mortality. Age, ill health and frailty all influence surgical decision‐making. Surgery has a negative impact on QoL and independence, which must be considered when counselling patients about choices.

Full paper BJS Breast cancer surgery in older women: outcomes of the Bridging Age Gap in Breast Cancer study

Further information on the project is available from the University of Sheffield’s Medical School Bridging the Age Gap in Breast Cancer