Afatinib

Afatinib outperforms gefitinib in Asian patients with EGFR-positive NSCLC

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The pan-ERB inhibitor afatinib improves progression-free survival (PFS), time-to-treatment failure (TTF) and objective response rate (ORR) compared with gefitinib among Asian patients with EGFR-positive non-small cell lung cancer (NSCLC) included in the LUX-Lung 7 trial. [APLCC 2016, ABS068]

“Median PFS and TTF were significantly longer with afatinib [11 and 13.7 months] than with gefitinib [10.9 and 11·5 months],” said study investigator Professor Kenneth O’Byrne, consultant medical oncologist at the Princess Alexandra Hospital in Brisbane, Queensland, Australia, at the recent APLCC 2016 held in Chiang Mai, Thailand. “Among Asian patients, PFS was prolonged by 24 percent. OS [overall survival] data are not mature yet.”

The secondary endpoint of ORR by independent review was also higher with afatinib (70 vs 56 percent for gefitinib). ORR in Asian patients was 70 percent with afatinib versus 57 percent for gefitinib.

“Results were consistent across all subgroups evaluated, including Asian patients,” O’ Byrne reported. “The improvement in efficacy was observed in both del19 and L858R populations.” Among Asian patients with del19 mutation, ORR was 72 and 68 percent, in favour of afatinib. In those with L858R mutation, ORR was also higher with afatinib (68 vs 42 percent with gefitinib).

Professor Kenneth O'Byrne

Professor Kenneth O’Byrne

LUX-Lung 7 was an international, phase IIb, randomized, open-label trial investigating the efficacy and safety of afatinib vs gefitinib in untreated patients with advanced, EGFR-positive NSCLC. The trial was done at 64 centres in 13 countries. [Lancet Oncol 2016;pii: S1470-2045(16)30033-X]

Patients were randomized to receive afatinib 40 mg once daily (n=160) or gefitinib 250 mg once daily (n=159) until radiological disease progression or beyond, by investigator decision. Median follow-up was 27.3 months. The coprimary endpoints were PFS by independent review, TTF, and OS. Over half of the participants were Asians (59 percent with afatinib; 55 percent with gefitinib). Baseline characteristics such as ethnicity and type of EGFR mutation were similar between arms.

“Adverse events in both groups were consistent with previous experience using the drugs and were manageable, leading to equally low rates of treatment discontinuation (6 percent for both),” said O’Byrne.

The most common grade ≥3 adverse events reported were diarrhoea, rash and acne with afatinib, and liver enzyme elevations with gefitinib.

“LUX-Lung 7 confirms the benefit of irreversible ErbB blockade with afatinib over reversible EGFR inhibition with gefitinib in the treatment of EGFR-positive NSCLC,” he concluded.

EU Okays Afatinib for NSCLC, Filgrastim and Defibrotide.

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The European Committee for Medicinal Products for Human Use (CHMP) has recommended that the targeted agent afatinib (Giotrif, Boehringer Ingelheim) be approved for use in nonsmall-cell lung cancer (NSCLC) that tests positive for EGFRmutations.

Afatinib was recently approved for this indication in the United States under the trade name Gilotrif.

This is the third drug to target EGFR mutations in NSCLC; it joins erlotinib (Tarceva) and gefitinib (Iressa). Both are available in most countries in the world, with one notable exception — gefitinib is not available in the United States.

About 10% to 15% of NSCLC is positive for EGFR mutations in Western populations; in Asian populations, the incidence is higher.

Filgrastim Biosimilar

The CHMP also recommended approval for the growth factor filgrastim (Grastofil, Apotex) for the treatment of neutropenia, which is a biosimilar to Neupogen (Amgen). “Studies have shown Grastofil to have a comparable quality, safety, and efficacy profile to Neupogen,” the committee noted.

Filgrastim is a granulocyte colony-stimulating factor that regulates the production and release of functional neutrophils from the bone marrow. It is used in cancer patients to counteract the myelosuppressive effects of chemotherapy by reducing the duration of neutropenia and the incidence of febrile neutropenia.

Change of Mind on Defibrotide

In addition, in its July meeting, the CHMP recommended the approval of defibrotide (Defitelio, Gentium) for use in the treatment of severe hepatic veno-occlusive disease, also known as sinusoidal obstructive syndrome, related to hematopoietic stem cell transplantation. The product has orphan drug status for this indication.

The CHMP issued a negative opinion on this product in March 2012. But at the request of the company, the committee re-examined its stance. After that re-examination, it issued a positive opinion for the very narrow indication of severe veno-occlusive disease.

The mechanism of action of defibrotide has not been fully elucidated, the committee notes in its summary. The drug increases the breakdown of blood clots, and it might also protect cells lining the blood vessels, it notes. The most common adverse events are hemorrhage, hypotension, and coagulopathy.

Source: Medscape.com