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: 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

Improved agreement means NICE now recommends lung cancer treatment osimertinib

NICE| 11 September 2020| Improved agreement means NICE now recommends lung cancer treatment

Thousands of people with non-small-cell lung cancer (NSCLC) will benefit from draft guidance published 11 September by NICE.

New draft guidance recommends osimertinib (also called Tagrisso and made by AstraZeneca) at two different places in the treatment pathway for locally advanced or metastatic epidermal growth factor receptor (EGFR)-positive NSCLC.

Around 1800 people in England have advanced EGFR-positive NSCLC, and the majority are set to benefit from the new recommendations.

The positive recommendation for untreated advanced EGFR-positive NSCLC follows a rapid review of NICE’s previous guidance, which did not recommend the treatment. The company has since offered an updated commercial arrangement meaning it is now a cost-effective use of NHS resources.

Additionally, NICE has recommended osimertinib for routine use on the NHS as a second-line treatment for patients with locally advanced or metastatic EGFR-positive NSCLC with the T790M mutation.

The treatment was previously available through the Cancer Drugs Fund for this group of patients, but has now been approved for routine commissioning on the NHS.

Osimertinib has shown the ability to improve the lives of patients with this devastating disease, and is likely to extend their time with loved ones. I know this news will be welcomed by patients and their families and carers.

Osimertinib has been available to patients with untreated EGFR-positive NSCLC throughout the COVID-19 pandemic as a part of the interim NHS England treatment regimen to allow flexibility for cancer patients. Patients with the T790M mutation have also had access to osimertinib as a second-line treatment via the Cancer Drugs Fund.

With the new draft guidance, new patients will now be eligible to receive osimertinib routinely (Source: NICE)

The guidance is expected to be published on 14 October 2020. Further information about the project is available from NICE

NICE recommends treatment for type of small-cell lung cancer

NICE  |  May 2020 | NICE recommends treatment for type of small-cell lung cancer

A new treatment option for patients with extensive-stage small-cell lung cancer has been approved by NICE.

In new draft guidance, atezolizumab (also called Tecentriq and made by Roche) with carboplatin and etoposide has been recommended as an option for untreated extensive-stage small-cell lung cancer (ES-SCLC).

Around 2400 people in England have ES-SCLC, of whom around 1200 people will be eligible for treatment with atezolizumab with carboplatin and etoposide.

The positive recommendation follows consultation on NICE’s previous draft guidance which did not recommend the treatment. The company has since agreed on a new price for atezolizumab with NHS England and Improvement, which means that the treatment is now considered a cost-effective use of NHS resources.

The clinical trial evidence for the combination treatment was based on patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Clinical experts suggested that the effects of the treatment may be different for people with a score of 2 or higher, that is, a more severe illness, so atezolizumab with carboplatin and etoposide was recommended only for patients with an ECOG performance status of 0 or 1.

Meindert Boysen, deputy chief executive officer and director of the Centre for Health Technology Evaluation at NICE, said: “We are pleased to be able to recommend this new treatment that could extend the life of patients with this type of lung cancer.

“I know how important this news will be for patients suffering with this condition, for which there are currently few treatment options. Atezolizumab with carboplatin and etoposide may offer valuable time for patients to spend with their loved ones.”

ES-SCLC is a form of lung cancer accounting for 1 in 8 lung cancer cases in the UK. It is an aggressive disease that progresses rapidly, with a significant negative impact on the quality of life of patients.

Clinical trial evidence suggests that atezolizumab with carboplatin and etoposide increases the time before the disease worsens by around 1 month compared with standard chemotherapy (5.2 months versus 4.3 months respectively).

It also suggests that atezolizumab plus carboplatin and etoposide increases overall survival compared with standard chemotherapy. However, the long-term benefit on overall survival was uncertain.

NICE expects to publish its final guidance on atezolizumab for ES-SCLC in June 2020 (Source: NICE)

Atezolizumab with carboplatin and etoposide for untreated extensive-stage small-cell lung cancer

NICE impact report: lung cancer

NICE impact reports review how NICE recommendations for evidence-based and cost-effective care are being used in priority areas of the health and care system, helping to improve outcomes where this is needed most. This report considers how NICE’s evidence based guidance can contribute to improvements in the care of people with lung cancer.

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Image source: https://www.nice.org.uk/

Lung cancer is the third most common cancer in England and is the leading cause of  cancer death. In 2017, there were almost 39,000 new cases of lung cancer and just over 28,000 related deaths.

Since 2005 and the publication of NICE’s first guideline on lung cancer, NICE has produced a suite of lung cancer related guidance, which aim to improve outcomes by focusing on survival rates and ensuring the most effective tests and treatments are used.

In England, overall survival rates for cancers are improving but there is still a marked difference between lung cancer and other cancers. Between 2012 and 2016 more than 95% of people with breast or prostate cancer survived more than 1 year after their diagnosis, compared to less than 40% of people with lung cancer.

There is an even greater difference between 5-year survival rates. More than 85% of people with breast or prostate cancer survived more than 5 years but just over 15% of people with lung cancer survived this long. When comparing with other countries in Europe, England’s long-term survival for people with lung cancer is poor, ranking 26th out of 29 countries.

Further detail at NICE

Full report: NICEimpact Lung Cancer

Exercise training improves physical capacity after lung cancer surgery

NIHR | September 2019| Exercise training improves physical capacity after lung cancer surgery

A new NIHR Signal showcases the findings of a Cochrane update which reviewed eight trials which combined aerobic and resistance exercise after lung cancer surgery. Although the trials were small in terms of participants (450 participants in total), they demonstrated consistent and meaningful improvements in exercise capacity. 

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Plain Language Summary

Exercise training after lung surgery for people with non‐small cell lung cancer

Review question

We updated the evidence about the effect of exercise training after lung surgery for non‐small cell lung cancer (NSCLC) on fitness level; adverse events; quality of life; strength of the leg, hand, and breathing muscles; breathlessness; fatigue; feelings of anxiety and depression; and lung function.

Background

After lung surgery for NSCLC, people’s fitness levels and quality of life decrease. We know that exercise training improves these outcomes in people with chronic lung disease and in those with prostate and breast cancer. In the 2013 version of this review, we demonstrated that exercise training improved fitness level (distance walked on the six‐minute walk test) in people after lung surgery for NSCLC. Due to the limited number of studies, the effect of exercise training on quality of life and other outcomes was unclear.

Search date

The evidence is current to February 2019.

Study characteristics

We included three studies from the 2013 review and an additional five new studies from the current review, for a total of eight studies with 450 participants (180 women). The number of participants in the included studies ranged between 17 and 131; the mean age of participants was between 63 and 71 years. Six studies explored the effects of combined aerobic and strengthening exercises; one explored the effects of combined aerobic exercise and inspiratory muscle training; and one explored the effects of combined aerobic exercise, strengthening exercise inspiratory muscle training and balance training. The length of the exercise programmes ranged from four to 20 weeks, with exercises performed twice to five days a week.

Key results

Our results showed that people with NSCLC who exercised after lung surgery had better fitness level (measured using both a cycling test and the six‐minute walk test) and strength in their leg muscles compared to those that did not exercise. We also showed initial evidence for better quality of life and less breathlessness in those who exercised. One adverse event (hip fracture) related to the intervention was reported in one study. The effect of exercise training after lung surgery on grip strength, fatigue, and lung function was uncertain. We found insufficient evidence for improvements in the strength of breathing muscles or feelings of anxiety and depression.

Quality of evidence

Overall the quality (certainty) of evidence for the outcomes was moderate, ranging between very low (for breathlessness) and high (for fitness level measured via the six‐minute walk test).

Full reference: Cavalheri, V. et al | 2019| Exercise training undertaken by people within 12 months of lung resection for non-small cell lung cancer | Cochrane Database Syst Rev|  Vol. 6 | doi/10.1002/14651858.CD009955.pub3/epdf/full

The full article is available to read from Cochrane 

Background: Decreased exercise capacity and health-related quality of life (HRQoL) are common in people following lung resection for non-small cell lung cancer (NSCLC). Exercise training has been demonstrated to confer gains in exercise capacity and HRQoL for people with a range of chronic conditions, including chronic obstructive pulmonary disease and heart failure, as well as in people with prostate and breast cancer. A programme of exercise training may also confer gains in these outcomes for people following lung resection for NSCLC. This systematic review updates our 2013 systematic review.

Objectives: The primary aim of this review was to determine the effects of exercise training on exercise capacity and adverse events in people following lung resection (with or without chemotherapy) for NSCLC. The secondary aims were to determine the effects of exercise training on other outcomes such as HRQoL, force-generating capacity of peripheral muscles, pressure-generating capacity of the respiratory muscles, dyspnoea and fatigue, feelings of anxiety and depression, lung function, and mortality.

Search Methods: We searched for additional randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2019, Issue 2 of 12), MEDLINE (via PubMed) (2013 to February 2019), Embase (via Ovid) (2013 to February 2019), SciELO (The Scientific Electronic Library Online) (2013 to February 2019), and PEDro (Physiotherapy Evidence Database) (2013 to February 2019).

Selection Criteria: We included RCTs in which participants with NSCLC who underwent lung resection were allocated to receive either exercise training, which included aerobic exercise, resistance exercise, or a combination of both, or no exercise training.

Data collection and analysis: Two review authors screened the studies and identified those eligible for inclusion. We used either postintervention values (with their respective standard deviation (SD)) or mean changes (with their respective SD) in the meta-analyses that reported results as mean difference (MD). In meta-analyses that reported results as standardised mean difference (SMD), we placed studies that reported postintervention values and those that reported mean changes in separate subgroups. We assessed the certainty of evidence for each outcome by downgrading or upgrading the evidence according to GRADE criteria.

Main results: Along with the three RCTs included in the original version of this review (2013), we identified an additional five RCTs in this update, resulting in a total of eight RCTs involving 450 participants (180 (40%) females). The risk of selection bias in the included studies was low and the risk of performance bias high. Six studies explored the effects of combined aerobic and resistance training; one explored the effects of combined aerobic and inspiratory muscle training; and one explored the effects of combined aerobic, resistance, inspiratory muscle training and balance training. On completion of the intervention period, compared to the control group, exercise capacity expressed as the peak rate of oxygen uptake (VO2peak) and six-minute walk distance (6MWD) was greater in the intervention group (VO2peak: MD 2.97 mL/kg/min, 95% confidence interval (CI) 1.93 to 4.02 mL/kg/min, 4 studies, 135 participants, moderate-certainty evidence; 6MWD: MD 57 m, 95% CI 34 to 80 m, 5 studies, 182 participants, high-certainty evidence). One adverse event (hip fracture) related to the intervention was reported in one of the included studies. The intervention group also achieved greater improvements in the physical component of general HRQoL; improved force-generating capacity of the quadriceps muscle; and less dyspnoea. We observed uncertain effects on the mental component of general HRQoL, disease-specific HRQoL, handgrip force, fatigue, and lung function. There were insufficient data to comment on the effect of exercise training on maximal inspiratory and expiratory pressures and feelings of anxiety and depression. Mortality was not reported in the included studies.

Authors’ Conclusions: Exercise training increased exercise capacity and quadriceps muscle force of people following lung resection for NSCLC. Our findings also suggest improvements on the physical component score of general HRQoL and decreased dyspnoea. This systematic review emphasises the importance of exercise training as part of the postoperative management of people with NSCLC.

Full details from NIHR 

New lung cancer treatment option approved by NICE

NICE | August 2019| New lung cancer treatment option approved by NICE

NICE has approved another new life-extending treatment for some people with lung cancer is to be made available on the Cancer Drugs Fund (CDF) following its approval by NICE in draft guidance

The immunotherapy drug pembrolizumab (also known as Keytruda) used with chemotherapy drugs carboplatin and paclitaxel will now be an option for adults with squamous non-small-cell lung cancer (NSCLC) which has spread to other parts of the body and who haven’t had any previous treatments.

lungs

Evidence from an ongoing clinical trial suggests that people who have pembrolizumab combination therapy could live longer than those who have standard chemotherapy. It also suggests people could have additional time without their cancer progressing compared with standard chemotherapy.

However, because the clinical evidence is immature, the cost-effectiveness estimates for pembrolizumab combination therapy are very uncertain. The committee recognised that it has the potential to be cost-effective, and therefore recommended it for use on the CDF. This will allow more evidence to be collected to address the uncertainties around overall survival.

Director of the NICE Centre for Health Technology Evaluation Meindert Boysen, said: ““The committee heard from the patient experts that people with squamous non-small-cell lung cancer often have a poor quality of life, and that treatments that have the potential to extend life would be of great importance.” (Source: NICE)

Full press release available from NICE

Read the draft guidance on pembrolizumab here

Lancet Study: Whole-body MRI scans are as accurate as standard imaging pathways for lung cancer staging

NIHR | July 2019 | Whole-body MRI scans are as accurate as standard imaging pathways for lung cancer staging

The latest Signal from the National Institute for Health Research (NIHR) highlights the findings of a study that reports using whole-body magnetic resonance imaging (MRI) in the initial investigation pathway is as good as standard pathways for detecting metastatic disease in adults with non-small-cell lung cancer. This NIHR-funded study also found that WB-MRI used for diagnosis and staging is quicker, cheaper and requires fewer other investigations than standard pathways.

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Although patients reported that having whole-body MRI was a greater burden than standard imaging, they generally preferred whole-body MRI if it reduced staging times. In theory, it may also reduce radiation exposure, as most people would not need to have a positron-emission tomography CT scan.

Current NICE guidance recommends a sequence of investigations for staging – assessing the extent of cancer in order to plan appropriate treatment. MRI of different areas of the body is only recommended after other imaging investigations. This study suggests that whole-body MRI could have a role earlier in the pathway (Source: NIHR).

Read the full Signal from NIHR

Full reference:

Taylor, S. et al | 2019|  Diagnostic accuracy of whole-body MRI versus standard imaging pathways for metastatic disease in newly diagnosed non-small-cell lung cancer: the prospective Streamline L trial| The Lancet Respiratory Medicine|523-532 | https://doi.org/10.1016/S2213-2600(19)30090-6

Background

Whole-body magnetic resonance imaging (WB-MRI) could be an alternative to multi-modality staging of non-small-cell lung cancer (NSCLC), but its diagnostic accuracy, effect on staging times, number of tests needed, cost, and effect on treatment decisions are unknown. We aimed to prospectively compare the diagnostic accuracy and efficiency of WB-MRI-based staging pathways with standard pathways in NSCLC.

Methods

The Streamline L trial was a prospective, multicentre trial done in 16 hospitals in England. Eligible patients were 18 years or older, with newly diagnosed NSCLC that was potentially radically treatable on diagnostic chest CT (defined as stage IIIb or less). Exclusion criteria were severe systemic disease, pregnancy, contraindications to MRI, or histologies other than NSCLC. Patients underwent WB-MRI, the result of which was withheld until standard staging investigations were complete and the first treatment decision made. The multidisciplinary team recorded its treatment decision based on standard investigations, then on the WB-MRI staging pathway (WB-MRI plus additional tests generated), and finally on all tests. The primary outcome was difference in per-patient sensitivity for metastases between standard and WB-MRI staging pathways against a consensus reference standard at 12 months, in the per-protocol population. Secondary outcomes were difference in per-patient specificity for metastatic disease detection between standard and WB-MRI staging pathways, differences in treatment decisions, staging efficiency (time taken, test number, and costs) and per-organ sensitivity and specificity for metastases and per-patient agreement for local T and N stage. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN50436483, and is complete.

Findings Between Feb 26, 2013, and Sept 5, 2016, 976 patients were screened for eligibility. 353 patients were recruited, 187 of whom completed the trial; 52 (28%) had metastasis at baseline. Pathway sensitivity was 50% for WB-MRI and 54% (41–67) for standard pathways, a difference of 4%. No adverse events related to imaging were reported. Specificity did not differ between WB-MRI (93% [88–96]) and standard pathways. Agreement with the multidisciplinary team’s final treatment decision was 98% for WB-MRI and 99% for the standard pathway. Time to complete staging was shorter for WB-MRI (13 days [12–14]) than for the standard pathway (19 days [17–21]); a 6-day (4–8) difference. The number of tests required was similar WB-MRI (one [1–1]) and standard pathways (one [1–2]). Mean per-patient costs were £317 (273–361) for WBI-MRI and £620 (574–666) for standard pathways.

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