BI’s afatinib LUX-Lung 8 trial data released at ASCO 2015

Patients from 23 countries, including India, participated in the trial, which is reportedly the first prospective trial to directly compare two different TKIs, afatinib and erlotinib By Viveka Roychowdhury

Patients from 23 countries, including India, participated in the trial, which is reportedly the first prospective trial to directly compare two different TKIs, afatinib and erlotinib By Viveka Roychowdhury

Cancer treatment is today based on greater understanding of both the histological as well as molecular classification of the disease. Hence research is aimed at discovering molecular targets and mutations which are linked to tumour growth.

Among the mutations most studied in non-small cell lung cancer (NSCLC), a specific type of lung cancer, is the over expression of Epidermal Growth Factor Receptors (EGFR), specifically the ErbB Family of receptors consisting of four related tyrosine kinases: EGFR (ErbB1), HER2 (ErbB2), ErbB3 and ErbB4. Thus the right tyrosine kinase inhibitor (TKI) treatment could potentially be a life saver for patients with such lung cancers and therefore a blockbuster molecule.

The battle for supremacy between TKIs went one step further at this year’s American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, US when Boehringer Ingelheim (BI) presented data from LUX-Lung 8, reportedly the first prospective trial to directly compare two different TKIs, afatinib and erlotinib, in patients with advanced squamous cell carcinoma (SCC) of the lung, progressing after treatment with first-line chemotherapy.

According to results presented by the company, treatment with afatinib significantly reduced the risk of death by 19 per cent, extending the survival of patients to a median of 7.9 months compared to 6.8 months on erlotinib. Afatinib also significantly improved control of cancer-related cough and shortness of breath compared to erlotinib, providing a better quality of life to patients.

SCC represents approximately 30 per cent of NSCLC which is the most common form of lung cancer comprising over 85 per cent of lung cancer cases.  Treatment options are reportedly limited and SCC of the lung is associated with a poor prognosis, with less than 5 per cent of patients with advanced SCC surviving for five years or longer. Thus even a small improvement in clinical outcomes, as shown in this trial, is big news for clinical oncologists and patients.

According to the World Cancer Research Fund International, lung cancer is the most common cancer in the world, with 1.8 million new cases diagnosed in 2012.

Mode of action

BI’s confidence that afatinib will be a breakthrough molecule is based on results from eight ongoing studies in the LUX-Lung clinical trial programme where it has been proved that unlike other TKIs, afatinib irreversibly blocks EGFR (ErbB1) as well as other members of the ErbB family that are known to play a critical role in the growth and spread of the most widespread cancers and cancers associated with high mortality (death).

Thus, according to a BI backgrounder, unlike other compounds which are reversible, afatinib aims to provide a sustained, selective and complete ErbB family blockade. The company believes that ‘afatinib’s unique mechanism of action could potentially lead to a greater overall effect on the tumour, preventing tumour cell growth and spread across a broad range of cancers, compared to other treatments which offer single, reversible, receptor blocking.’

Approval of afatinib in this indication was based on the primary endpoint of PFS from the LUX-Lung 3 clinical trial where afatinib significantly delayed tumour growth when compared to standard chemotherapy. In addition, afatinib is the first treatment to show an OS benefit for patients with specific types of EGFR mutation-positive NSCLC compared to chemotherapy. A significant OS benefit was demonstrated independently in the LUX-Lung 3 and six trials for patients with the most common EGFR mutation (exon 19 deletions; del19) compared to chemotherapy.

Benefits for lung cancer patients in India

Of the nine abstracts presented by BI at this year’s ASCO meet, the LUX-Lung 8 trial holds special significance for lung cancer patients in India. The incidence of lung cancer in India is projected to increase, primarily due to smoking habits. According to India’s National Cancer Registry Programme’s Three Year Report of Population Based Cancer Registries spanning 2009-2011, lung cancer constitutes 6.9 per cent of all new cancer cases in the country and 9.3 per cent of all cancer related deaths in both sexes. Moreover, it is the commonest cancer and cause of cancer related mortality in men.

Afatinib is approved in more than 50 countries for the first-line treatment of distinct types of EGFR mutation-positive NSCLC (as GIOTRIF in the European Union, Japan, Taiwan and Canada and as GILOTRIF in the US.) Afatinib’s approval in India, as XOVOLTIB, last November was an important milestone in BI India’s journey as it marked BI India’s entry into oncology.

The LUX-Lung 8 trial included 795 patients from 23 countries, including India, with advanced SCC of the lung, previously treated with first-line platinum-based chemotherapy who were randomised 1:1 to receive either afatinib or erlotinib treatment.

According to company sources, in India, afatinib/ Xovoltib is priced at 13.8 per cent to the US price. This makes Xovoltib’s maximum retail price similar to the price to patient of other innovator TKIs in lung cancer. Afatinib has a different brand name in India (Xovoltib) as compared to Giotrif/ Gilotrif in other countries due the India-friendly pricing strategy adopted by the company. The company is reportedly working on other options to improve access for patients.

(The author attended ASCO 2015 as a BI invitee)

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