PFS results showed that afatinib had met the investigator’s hypothesis, significantly prolonging median PFS compared to pemetrexed/cisplatin (11.1 vs 6.9 months; HR=0.58; P=0.0004). The greatest prolongation of median PFS was observed in 308 patients with the common EGFR-activating Dell9/L858R mutations (13.6 vs 6.9 months for pemetrexed + cisplatin; HR=0.47; P<0.0001). Afatinib was also generally better tolerated than pemetrexed/cisplatin in this population, with drug-related adverse event discontinuation rates of 8% and 11.7%, respectively. However, the investigators reported that approximately half of the patients in the afatinib-arm had drug-related adverse events of grade 3 or higher, but noted that median follow-up was 16 cycles vs only 6 cycles for chemotherapy, so there was a longer period to detect AEs in the afatinib-treated group.
LUX-Lung 3 is the largest prospective trial to date, of EGFR mutation-positive lung cancer, and is the first study using pemetrexed/cisplatin as a comparator. Based on the results of this trial, and possibly other trials that demonstrated the efficacy of afatinib in patients with EGFR mutation-positive, recurrent or metastatic squamous cell carcinoma of the head and neck, it is likely that afatinib will be used as a first-line therapy for the treatment of EGFR-activating mutation positive NSCLC.5
Finally, the incidence of NSCLC is greatest in the elderly population. A study focused on treatment of the frailest, elderly NSCLC patients entitled “Weekly nab-paclitaxel in combination with carboplatin as first-line therapy in elderly patients with advanced non-small cell lung cancer (NSCLC),” was presented at ASCO 2012 by lead author Mark A. Socinski, MD, of the University of Pittsburgh Medical Center Cancer Pavilion, Pittsburgh, PA.6
“Median age of lung cancer is 70, so half of our patients are over the age of 70. This patient population is generally undertreated, with only approximately 30% receiving systemic therapy,” noted Dr. Socinski. He added that “Developing novel therapies that can give them greater benefit, and also at the same time are somewhat less toxic in this population, because obviously the older patients may be more prone to the side effects of chemotherapy than younger patients.”
This study provided an analysis of efficacy and safety of a Phase 3 trial comparing nab-paclitaxel (nab-P, albumin-bound paclitaxel particles) plus carboplatin (C) to solvent-based paclitaxel (sb-P) plus carboplatin in patients with advanced NSCLC that are ≥70 and <70 years of age.
“The observation that we had in this trial was that the nab-paclitaxel arm in the elderly population had a significantly increased survival, experiencing a 19.9-month median survival with nab-paclitaxel vs 10.4 months with solvent-based paclitaxel. Obviously this was not an expected finding, but this was an encouraging finding,” said Dr. Socinski. He added that follow-up studies will be performed to see if this is a real observation or just a misleading finding from this particular subgroup analysis.