New combination treatment for metastatic lung cancer patients approved for use on the NHS in England and Wales
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New combination treatment for metastatic lung cancer patients approved for use on the NHS in England and Wales
EMBARGOED UNTIL 00:00, 2 May 2019, Welwyn Garden City – The National Institute for Health and Care Excellence (NICE) has recommended Tecentriq®▼ (atezolizumab) in combination with Avastin® (bevacizumab), carboplatin and paclitaxel (chemotherapy) as an option for metastatic non-squamous non-small cell lung cancer (NSCLC) in adult patients who have not had treatment for their metastatic NSCLC before and whose PD-L1 expression is low or negative. The recommendation is also for those with EGFR or ALK-positive mutations, who have failed on a previous targeted therapy.[i] Available today, it is estimated around 4,800 patients with advanced NSCLC could benefit from this combination.[ii],[iii]
The decision is based on data which showed people treated with atezolizumab plus bevacizumab and chemotherapy lived longer versus those treated with bevacizumab plus chemotherapy.1
Over 46,000 new cases of lung cancer are diagnosed in the UK each year and around 87% of these cases are NSCLC.[iv],[v] Up to 15% of lung cancers are caused by EGFR or ALK-positive mutations as a result of gene alterations.[vi]
“This decision by NICE is fantastic news for people living with metastatic NSCLC in England and Wales, where the current outlook is generally poor. For patients to have access to a life-extending treatment is an important step forward in order to advance outcomes in this area. Every additional day of life provides more opportunities to share time with their families, their friends and loved ones,” said Paula Chadwick, CEO of the Roy Castle Lung Cancer Foundation.
“This decision is an excellent example of the way NICE and industry work together to make clinically effective treatments available on the NHS. The combination of chemotherapy with atezolizumab, which helps the body’s immune system to destroy cancer cells and bevacizumab, which blocks VEGF, a molecule which stops immune cells from functioning properly, has been shown to significantly improve progression-free survival and overall survival among patients with metastatic non-squamous NSCLC, compared to patients who received bevacizumab and chemotherapy alone. This was regardless of PD-L1 expression and EGFR or ALK genetic alteration status. Of note, the combination has been shown to be effective in NSCLC patients with either EGFR mutations or liver metastases, who typically have a poor prognosis, and could become a new standard of care for these two important patient subgroups,” said Gary Middleton, Professor of Medical Oncology at the University of Birmingham.
Atezolizumab is a cancer immunotherapy. It disarms the cancer of its cloak, which allows the body's smartest medicine - the immune system - to detect and destroy it. Atezolizumab blocks PD-L1 – an important ligand found on the surface of cancer cells that camouflage them from detection and destruction by the immune system.[vii]
Atezolizumab is indicated for the following:
- As monotherapy for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC):
- after prior platinum-containing chemotherapy, or
- who are considered cisplatin ineligible, and whose tumours have a PD-L1 expression ≥ 5%
- As monotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC after prior chemotherapy. Patients with EGFR activating mutant or ALK‑positive NSCLC should also have received targeted therapies before
- In combination with bevacizumab, paclitaxel and carboplatin, for the first-line treatment of adult patients with metastatic NSCLC. Patients with EGFR mutant or ALK-positive NSCLC, must have failed appropriate targeted therapies
About Lung Cancer
Over 46,000 new cases of lung cancer are diagnosed in the UK each year, with over 35,800 deaths annually.2 The prognosis for lung cancer patients is often poor, with fewer than 5% of all lung cancer patients surviving for ten years, experiencing high rates of recurrence and treatment resistance.[viii],[ix]
About 87% of lung cancers in the UK are non-small-cell lung cancer (NSCLC). There are three common types of NSCLC (adenocarcinoma, squamous cell carcinoma, and large cell carcinoma), all grouped together because they behave and respond to treatment in a similar way.3
- IMpower150 is a multi-centre, ongoing randomised, open-label, controlled Phase III study evaluating the efficacy and safety of atezolizumab in combination with chemotherapy (carboplatin and paclitaxel) with or without bevacizumab in people with metastatic non-squamous NSCLC who had not previously been treated with chemotherapy (first-line). Patients with EGFR activating/ALK positive tumour were included if they had disease progression or failed on previous tyrosine kinase inhibitor(s).[x] Patients were split into three arms:
- Arm A: atezolizumab plus carboplatin and paclitaxel (ACP)
- Arm B: atezolizumab and bevacizumab plus carboplatin and paclitaxel (ABCP)
- Arm C: bevacizumab plus carboplatin and paclitaxel (BCP)
- The positive recommendation from NICE is for the ABCP arm of study IMpower150
- The co-primary endpoints of OS and PFS in the intent-to-treat wild type (ITT-WT) were positive for Arm B (ABCP) vs Arm C (BCP) for this study. The median PFS was 8.3 months in the patients treated with ABCP compared to 6.8 months in patients treated with BCP alone (HR: 0.62 (95% CI, 0.52-0.74)).8 The median OS among patients treated with ABCP was 19.2 months compared with 14.7 months for people treated with BCP alone (HR: 0.78 (95% CI 0.64-0.96)).8
- Pre-planned subgroup analyses of the patients in the intention-to-treat population who had liver metastases at baseline (109 of 800 patients) showed patients treated with ABCP achieved a median overall survival of 13·3 months versus 9·4 months with BCP (HR 0·52 (95% CI 0·33–0·82).[xi]
- Pre-planned analysis of the IMpower150 study showed patients with EGFR activating/ALK positive tumour treated with ABCP achieved a median PFS of 9.7 months vs 6.1 months in patients treated with BCP alone (HR=0.59; 95% CI 0.37-0.94).8 Median OS in patients treated with ABCP was not reached (95% CI 17.0, NE), compared to 17.5 months in people treated with BCP alone (95% CI 10.4, NE), HR 0.54 (0.29, 1.03).[xii]
- Atezolizumab in combination with carboplatin and paclitaxel with or without bevacizumab was generally well tolerated, and safety was consistent with the known risks of each study treatment.8,10
- The most common adverse events (≥ 20%) in the IMpower 150 trial were peripheral neuropathy (42.6%), nausea (35.6%), anaemia (32.7%), neutropenia (32.4%), rash (29.8%), fatigue (29.6%), constipation (27.2%), decreased appetite (26.2%), diarrhoea (26.0%), thrombocytopenia (24.0%), arthralgia (23.8%).[xiii]
- Grade 3 - 4 adverse events were 56% in the ABCP arm versus 48% in the BCP arm. The most common grade 3 or 4 treatment-related adverse events were neutropenia, decreased neutrophil count, febrile neutropenia, and hypertension. Treatment-related deaths occurred in 11 patients (2.8%) in the ABCP group and in 9 patients (2.3%) in the BCP group. Treatment-related serious adverse events were noted in 25.4% of the patients in the ABCP group and in 19.3% of those in the BCP group. A total of 77.4% of the immune-related adverse events that occurred in the ABCP group were grade 1 or 2 and none were grade 5.8
- The most common immune-related adverse events were rash, hepatitis, hypothyroidism, hyperthyroidism, pneumonitis, and colitis.8
Roche is a pioneer in pharmaceuticals and diagnostics, focused on advancing science to improve people’s lives. We have created truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. In the UK we employ over 2,000 people who work hard every day to bring our medicines and diagnostics to people who urgently need them. We work from bench to bedside - researching new medicines and diagnostics, running global clinical trials, and collaborating with the NHS to try to ensure rapid uptake and delivery of our products and services.
In 2017, our total research and development investment in the UK amounted to £338million and we conducted over 181 clinical trials with 10,600 participants. In 2018, we worked together with NICE and NHS England to ensure eight of our new treatments were made available on the NHS. Our drive, every day, is to ensure our medicines reach those who need them as soon as possible. For more information: www.roche.co.uk
Adverse reaction reporting
This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme: website www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Adverse events should also be reported to Roche Products Ltd. Please contact Roche Drug Safety Centre by emailing firstname.lastname@example.org or calling +44(0)1707 367554.
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[i] NICE (2019). Final appraisal document: Atezolizumab for treating metastatic non-squamous non-small-cell lung cancer. May 2019
[ii] Office for National Statistics. Population Estimates for UK, England and Wales, Scotland and Northern Ireland [Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/populationestimatesforukenglandandwalesscotlandandnorthernireland.
[iii] Royal College of Physicians. UK National Lung Cancer Audit 2018 [Available from: https://www.rcplondon.ac.uk/projects/national-lung-cancer-audit
[iv] Cancer Research UK. Lung Cancer Statistics. Available at: http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer#heading-One [Last accessed: May 2019]
[v] Cancer Research UK. Lung cancer stages, types and grades. Available at: www.cancerresearchuk.org/about-cancer/lung-cancer/stages-types-grades/types [Last accessed: May 2019]
[vi] EGFR and ALK - About targeted cancer drugs - Advanced lung cancer treatment. Cancer Research UK. 2017 [Last accessed: May 2019]
[vii] National Cancer Institute (2016) Definition of atezolizumab. NCI Drug Dictionary. [online] Available at: www.cancer.gov/publications/dictionaries/cancer-drug?CdrID=702758 [Last accessed: May 2019]
[viii] Tsvetkova and Goss. Drug resistance and its significance for treatment decisions in non-small-cell lung cancer. Curr Oncology. 2012;19(Suppl 1):S45–S51.
[ix] Froudarakis, M., and Briasoulis, E. (2010). Advanced non-small cell lung cancer: on relapse rechallenge the tumor, not the patient. BioMed Central Research Notes. 3, 195. Available at: www.ncbi.nlm.nih.gov/pmc/articles/PMC2914654/ [Last accessed: May 2019]
[x] Socinski MA et al. N Engl J Med; 378 (June 2018) 2288-2301
[xi] Reck M et al. Lancet Respir Med 2019; 7: 387–401
[xii] Socinski MA et al. Journal of Clinical Oncology 36, no.15 suppl (May 2018) 9002-9002.
[xiii] 09/08/2018 Tecentriq - EMEA/H/C/004143 - N/0015