Published today in The New England Journal of Medicine, a multi-center phase I clinical study conducted across 11 countries, co-authored by Enriqueta Felip, Principal Investigator of VHIO´s Thoracic Tumors Group, represents an important step forward in the treatment of patients with ALK-rearranged lung cancer.
Up until now, the targeted cancer drug crizotinib, which received accelerated approval to treat ALK- positive non-small cell lung cancer (NSCLC) in 2011, has constituted the standard treatment option for patients suffering with this particular form of lung cancer due to its efficacy in triggering rapid tumor regression. Such effectiveness, as with other drugs directed against cancer-driving gene mutations, has since unfortunately proved temporal.
These patients invariably and ultimately develop resistance to crizotinib, and typically relapse after around 8 months, leaving them with very few alternative treatment options and consequently, little hope. Novel agents aimed at suppressing the growth of recurrent cancers are therefore critical in order to further advance and exact the treatment and care of these patients.
Preclinical studies previously proposed one such promising contender, ceritinib. With a different molecular make-up from crizotinib, preclinical studies indicated that it would be effective in both crizotinib-sensitive and crizotinib-resistant tumors.
Enrolling at total of 130 patients, 23 of whom were recruited from the Vall d´Hebron University Hospital, this current, inspired early-phase clinical study was designed to both assess the agent´s safety and tolerability, as well as observe and measure its efficacy and antitumor activity in humans. Ceritinib not only induced remissions in almost 60% of patients with ALK-rearranged lung cancer, but importantly, responses were independent of whether patients had been treated with crizotinib previously, suggesting refreshed hope of response after relapse occurs following crizotinib treatment. Adverse events were reported as mild, manageable, and resolved when dosage levels were adjusted to alleviate side effects.
“These results show great promise since they open up a new avenue for the future treatment of patients developing resistance to crizotinib. Importantly up until now, there was no other alternative available for these patients,” explains co-author Eriqueta Felip.
To access the original paper* and consult the accompanying editorial**, please visit The New England Journal of Medicine website.
* Alice T. Shaw, M.D., Ph.D., Dong-Wan Kim, M.D., Ph.D., Ranee Mehra, M.D., Daniel S.W. Tan, M.B., B.S., Enriqueta Felip, M.D., Ph.D., Laura Q.M. Chow, M.D., D. Ross Camidge, M.D., Ph.D., Johan Vansteenkiste, M.D., Ph.D., Sunil Sharma, M.D., Tommaso De Pas, M.D., Gregory J. Riely, M.D., Ph.D., Benjamin J. Solomon, M.B., B.S., Ph.D., Juergen Wolf, M.D., Ph.D., Michael Thomas, M.D., Martin Schuler, M.D., Geoffrey Liu, M.D., Armando Santoro, M.D., Yvonne Y. Lau, Ph.D., Meredith Goldwasser, Sc.D., Anthony L. Boral, M.D., Ph.D., and Jeffrey A. Engelman, M.D., Ph.D. Ceritinib in ALK-Rearranged Non–Small-Cell Lung Cancer. N Engl J Med 2014; 370:1189-1197 March 27, 2014
** Thomas, Roman K. (2014) Overcoming Drug Resistance in ALK-Rearranged Lung Cancer. N Engl J Med 2014; 370:13, 1250-1251.