Alectinib provides longer symptom improvement than crizotinib in ALK-positive lung cancer

April 12, 2018, European Society for Medical Oncology

Alectinib provides longer symptom improvement than crizotinib in ALK-positive non-small-cell lung cancer (NSCLC), according to results from the ALEX trial presented at the ELCC 2018 (European Lung Cancer Congress) in Geneva, Switzerland.

The phase III ALEX trial was a head-to-head comparison of the next-generation tyrosine kinase inhibitor (TKI) alectinib versus the standard of care TKI crizotinib in with anaplastic lymphoma kinase (ALK)-positive NSCLC, dependent on a rearrangement of the ALK gene. Approximately 4% of NSCLC patients are ALK-positive and are at high risk of central nervous system (CNS) metastases. Alectinib improved progression-free survival and prolonged the time to CNS progression compared to crizotinib. Alectinib had a better toxicity profile than crizotinib despite a longer duration of treatment.

Patient-reported outcomes in terms of health-related quality of life and cancer-related symptoms with alectinib and crizotinib are reported for the first time at ELCC. The EORTC QLQ-C30 questionnaire was used to evaluate health-related quality of life and the EORTC QLQ-LC13 questionnaire was used to assess lung cancer-related symptoms. Patients completed the questionnaires at baseline, every four weeks during treatment, within the four weeks after study withdrawal, and after disease progression. The reasons for withdrawal have been previously reported; very few were due to symptom deterioration in either group.

Around two-thirds of patients in both treatment groups completed the questionnaires (66% and 64% in the alectinib and crizotinib groups, respectively). Patients in both the alectinib and crizotinib treatment groups had clinically meaningful improvements in health-related quality of life. However, there was a longer duration of improvement in health-related quality of life for patients treated with alectinib (88 weeks) compared to crizotinib (68 weeks).

For the patients with CNS metastases at baseline, a lower proportion of patients in the alectinib arm had worsening in health-related quality of life compared with crizotinib starting at week four (10.8% vs. 20.6%) and persisting for most assessments through week 84 (0% vs. 16.7 %). In addition, a lower proportion of these patients reported worsening in cognitive function with alectinib compared to crizotinib (17.9% vs. 34.6% at week 32, respectively).

Regarding lung cancer symptoms, there was a clinically meaningful improvement in both treatment arms. But the duration of improvement was longer with alectinib compared to crizotinib (cough: 96 versus 84 weeks; chest pain: 96 versus 80 weeks; fatigue: 96 versus 68 weeks; pain in other parts: 96 versus 68 weeks, respectively).

Fewer patients in the alectinib group reported a clinically meaningful worsening in treatment-related symptoms such as diarrhoea, peripheral neuropathy, constipation, dysphagia, appetite loss, and nausea/vomiting.

Lead author Dr Maurice Pérol, medical oncologist, Centre Léon Bérard, Lyon, France, co-chair of ELCC 2018, said: "The patient-reported outcome data is consistent with the main results of the study. The primary analysis showed a similar response rate for crizotinib and alectinib, but a longer duration of response with alectinib. This is consistent with the improvements in health-related quality of life and lung cancer symptoms, which were of similar magnitude in both groups but lasted longer with alectinib."

"The high level of CNS activity shown with alectinib in the primary analysis is consistent with the fact that fewer patients treated with alectinib reported clinically meaningful worsening in health-related quality of life or cognitive function compared to crizotinib," he continued. "Finally, the superior tolerability profile of alectinib compared to crizotinib shown in this analysis is consistent with the adverse events profile recorded during the study."

Pérol said: "The patient-reported outcome data supports the use of alectinib as a new standard of care in the frontline treatment of patients with ALK-positive lung cancer."

Commenting on the study, Dr Fiona Blackhall, Honorary Consultant in Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK, said: "The ALEX trial was a practice-changing study that firmly placed alectinib as a first-line palliative treatment for ALK-positive patients. This secondary analysis strengthens the rationale for alectinib as the standard of care in first-line treatment."

Blackhall said that increasingly, because of the cost of conducting clinical trials, patient-reported outcomes are not measured. But she said: "In this context of palliating advanced lung cancer, living better is as important, if arguably not more important, than living longer. And for this reason, patient-reported outcomes and health-related quality of life are crucial to assess and analyse."

She continued: "In patients with advanced lung cancer the burden is high, particularly cough, breathlessness and chest pain. And so to have meaningful palliation and improvement in symptoms is of paramount importance. So alongside wishing to identify drugs that improve progression-free survival and overall survival ultimately, we need to ensure that those drugs also allow patients to live better. Goals of care are important in the everyday management of patients with lung cancer and alleviating the symptoms it causes is a key goal."

Regarding the impact of alectinib on symptoms in the ALEX trial, Blackhall said: "The time to deterioration in common and difficult to palliate symptoms including cough, dyspnoea, and chest pain was comparable between alectinib and . However, alectinib prolonged the improvement in those symptoms. That fits in with the previously reported improvement in progression-free survival and favourable tolerability with alectinib."

Explore further: Alectinib: ALEX and ALUR trials show CNS benefit in NSCLC

More information: References:

1. Abstract 138PD_PR "Patient-reported outcomes (PROs) in ALEX: A phase III study of alectinib (ALEC) vs crizotinib (CRIZ) in non-small-cell lung cancer (NSCLC)" presented by Maurice Pérol during the Poster Discussion session "Immunotherapy and next-generation TKIs: from second to frontline treatment" on Thursday 12 April, 07:45 to 09:00 (CEST) in Room A.
Journal of Thoracic Oncology, Volume 13, Issue 4, Supplement, April 2018.

2. Peters S, Camidge DR, Shaw AT, et al. Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2017;377(9):829–838.
DOI: 10.1056/NEJMoa1704795.

Related Stories

Alectinib: ALEX and ALUR trials show CNS benefit in NSCLC

September 6, 2017
Data from two separate phase 3 studies to be presented at the ESMO 2017 Congress in Madrid, show alectinib's particular central nervous system (CNS) activity in patients with advanced non-small cell lung cancer involving ...

Alectinib halts lung cancer growth more than a year longer than crizotinib

June 5, 2017
Findings from a phase III clinical trial point to a more effective initial treatment for patients with ALK-positive non-small cell lung cancer (NSCLC). Compared to the current standard of care crizotinib (Xalkori), the newer ...

Study shows alectinib 600 mg more effective than crizotinib in Asian cancer patients

November 17, 2017
A subanalysis of the phase III ALEX study has shown that alectinib 600 mg twice daily is more effective than standard of care crizotinib in Asian patients with anaplastic lymphoma kinase (ALK) positive non-small-cell lung ...

FDA continues recent trend of approval with new second generation lung cancer treatment

December 23, 2015
The International Association for the Study of Lung Cancer (IASLC) is once again gratified to see the approval of a new second-generation lung cancer treatment that can help many patients in their battle against the disease. ...

Identification of mutations causing lung cancer resistance leads to new treatment strategies

September 17, 2014
Two mutations that cause lung cancer resistance to the investigational ALK inhibitor alectinib were identified, and this information may help design new treatment regimens for patients with ALK-positive lung cancer, according ...

Phase III trial shows crizotinib superior to single-agent chemotherapy for ALK-positive lung cancer

September 30, 2012
The results of a new phase III trial show that crizotinib, a targeted therapy, is a more effective treatment than standard chemotherapy for patients with advanced, ALK-positive lung cancer, researchers said at the ESMO 2012 ...

Recommended for you

Pushing closer to a new cancer-fighting strategy

December 11, 2018
A molecular pathway that's frequently mutated in many different forms of cancer becomes active when cells push parts of their membranes outward into bulging protrusions, Johns Hopkins researchers report in a new study. The ...

Scientists have identified and modelled a distinct biology for paediatric AML

December 11, 2018
Scientists have identified and modelled a distinct biology for paediatric acute myeloid leukaemia, one of the major causes of death in children.

HER2 mutations can cause treatment resistance in metastatic ER-positive breast cancer

December 11, 2018
Metastatic breast cancers treated with hormone therapy can become treatment-resistant when they acquire mutations in the human epidermal growth factor receptor 2 (HER2) that were not present in the original tumor, reports ...

Loss of two genes drives a deadly form of colorectal cancer, reveals a potential treatment

December 11, 2018
Colorectal cancers arise from earlier growths, called polyps, found on the inner surface of the colon. Scientists are now learning that polyps use two distinct molecular pathways as they progress to cancer, called the "conventional" ...

Successful anti-PD-1 therapy requires interaction between CD8+ T cells and dendritic cells

December 11, 2018
A team led by a Massachusetts General Hospital (MGH) investigator has found that successful cancer immunotherapy targeting the PD-1 molecule requires interaction between cytotoxic CD8+ T cells, which have been considered ...

Taking uncertainty out of cancer prognosis

December 11, 2018
A cancer diagnosis tells you that you have cancer, but how that cancer will progress is a terrifying uncertainty for most patients. Researchers at Cold Spring Harbor Laboratory (CSHL) have now identified a specific class ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.