Afatinib monotherapy in EGFR-mutant lung adenocarcinoma

Afatinib monotherapy in EGFR-mutant lung adenocarcinoma

News Lenalidomide as first-line therapy for elderly CLL patients Two-thirds of all patients who are newly diagnosed with chronic lymphocytic leukaemia...

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Lenalidomide as first-line therapy for elderly CLL patients Two-thirds of all patients who are newly diagnosed with chronic lymphocytic leukaemia (CLL) are older than 65 years, but these individuals are infrequently represented in clinical trials. No consensus exists on the best first-line therapy for CLL in elderly patients, a population who often experience treatment-limiting toxicities with the therapeutic regimens that are effective in younger patients. A recent single-group phase 2 clinical trial studied single-agent lenalidomide as initial therapy for symptomatic CLL in treatment-naive patients older than 65 years (median age 71 years). The investigators reported that longlasting responses were induced by long-term treatment with this oral immunomodulatory agent with continuous daily dosing at a median of 5 mg. After a median follow-up of 4 years, overall survival was 82% in the 60 patients enrolled in the study,

and 35 (58%) of the participants were long-term responders, whose response lasted longer than 36 months. Median time to treatment failure had not yet been reached. All long-term responders experienced neutropenia, with 12 patients having grade 3–4 severity during the first 12 months of treatment. However, this was resolved in 29 of the 35 patients (including all grade 3–4), mostly through dose reduction. “In CLL, it’s very important to show how durable the treatment is”, said senior author Alessandra Ferrajoli (The University of Texas MD Anderson Cancer Center, Houston, TX, USA). With this study, “the patients had responses to lenalidomide that were durable, there was a good survival rate, and the benefit of increases in immunoglobulin levels was maintained.” Ferrajoli added that studies are ongoing, including “a large, global

trial currently comparing singleagent lenalidomide to a more conservative standard therapy in elderly patients”. “I am thrilled with this publication”, Nicole Lamanna (Columbia University Medical Center, New York, NY, USA) told The Lancet Oncology. “For older patients with CLL, often we would like to avoid aggressive chemotherapy as the treatment is often too myelosuppressive and immunosuppressive. Lenalidomide is an oral therapy, and toxicities are much less than seen with traditional chemotherapies. This is an alternate approach we can offer older patients with CLL who cannot tolerate more traditional regimens. This study has shown that for patients on long-term therapy their response can improve the longer they continue therapy.”

Published Online July 5, 2013 S1470-2045(13)70330-9 For the study see Blood 2013; published online June 25. http:// bloodjournal.hematologylibrary. org/content/early/2013/06/25/ blood-2013-04-495341

Judith A Gilbert

In a prospective randomised phase 3 clinical trial, investigators compared afatinib with the combination of pemetrexed and cisplatin as initial therapy for patients with advanced lung adenocarcinoma harbouring activating EGFR mutations. They reported that progression-free survival was significantly longer with afatinib than with pemetrexed–cisplatin (median 11·1 months vs 6·9 months; hazard ratio 0·58, 95% CI 0·43–0·78; p=0·001), and response rates were substantially higher (56% vs 23%). Worsening of lung cancer-related symptoms was significantly delayed with afatinib compared with pemetrexed–cisplatin. Pemetrexed plus cisplatin has become a standard first-line chemotherapy for advanced lung adenocarcinoma. Conversely, afatinib is a selective inhibitor that irreversibly binds to members of the ErbB family, and has shown preclinical and clinical activity Vol 14 August 2013

against lung cancers harbouring the EGFR Thr790Met resistance mutation. Study participants were randomly assigned to receive oral afatinib (40 mg) once daily or intravenous pemetrexed (500 mg/m2) and cisplatin (75 mg/m2) every 21 days for a maximum of six cycles. The global trial included 345 treatment-naive patients with stage IIIB or IV disease. First author Lecia Sequist (Massachusetts General Hospital, Boston, MA, USA) said, “There are two things that are new about this study. This is the first study comparing afatinib with combination chemotherapy for the treatment of EGFR-mutationpositive lung adenocarcinoma, as well as the first study comparing an EGFR inhibitor to the combination of pemetrexed and cisplatin.” She continued: “This study confirms that mutation-directed treatment is the best way to go, even compared with the

pemetrexed–cisplatin combination”. Furthermore, “patients on afatinib had improved quality of life compared with patients on pemetrexed–cisplatin”. “The future direction of treatment for advanced lung adenocarcinomas is to individualise care based on the understanding of the oncogenic driver of the tumour”, Nasser Hanna (Indiana University School of Medicine, Indianapolis, IN, USA) told The Lancet Oncology. “A limitation on this targeted approach is that adenocarcinomas are often complex tumours in which finding single drivers will be more challenging.” Hanna added that the next step for establishing which EGFR inhibitor has a therapeutic advantage in treating EGFRmutant adenocarcinomas would be to compare them directly in the same trial for efficacy, cost, and side-effects.

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Afatinib monotherapy in EGFR-mutant lung adenocarcinoma

Published Online July 12, 2013 S1470-2045(13)70346-2 For the study see J Clin Oncol 2013; published online July 1. DOI:10.1200/JCO.2012.44.2806

Judith A Gilbert e345