A recent article published in J Clin Oncol reviews the treatment options for elderly patients with non-small cell lung cancer, and this article excerpts its targeted therapy and adjuvant chemotherapy sections. Targeted therapy in elderly patients with metastatic non-small cell lung cancer When combined with paclitaxel and carboplatin, bevacizumab improved overall survival from 10.3 to 12.3 months in patients with metastatic nonsquamous non-small cell lung cancer (HR for death, 0.79, P = .003). However, four subgroup analyses in older patients could not conclusively confirm the efficacy. First, in a post hoc subgroup analysis of patients aged 70 years and older who were studied (224; 26%), Ramalingam et al reported a trend toward a higher bevacizumab response rate (29% v 17%, P = .067) and improved progression-free survival (5.9 v 4.9 months; P = .063). Overall survival was similar in older patients (11.3 months v 12.1 months, P = .4). However, grade 3 or higher adverse events, including death, occurred in 87% of bevacizumab-treated patients compared with 61% of patients not receiving bevacizumab (P = .001). Second, the AVAIL (Avastin Lung Cancer Study) trial provided a similar subgroup analysis of patients aged 65 years and older (304 patients). AVAIL was a phase III clinical trial comparing bevacizumab with cisplatin and gemcitabine, with conventional chemotherapy and placebo. Low-dose bevacizumab (7.5 mg/kg every 3 weeks) improved progression-free survival (HR, 0.71, P = .023), but higher doses (15 mg/kg every 3 weeks) did not (HR, 0.84; P = 0.26). The incidence of bevacizumab adverse events was similar between older and younger patients. However, this subgroup analysis did not show an improvement in survival with bevacizumab in older patients. Third, the Avastin Lung Cancer Safety Study analyzed 2,212 patients given bevacizumab first-line therapy and analyzed its safety. In the subgroup analysis, 623 patients, all aged 65 years and older, had similar rates of adverse reactions as younger patients, but older patients had a more frequent rate of serious adverse events (45.3%: 34.7%). Finally, Socinski et al. performed an age-based subgroup analysis of a phase III study (which analyzed various drugs in combination with bevacizumab). While prolonged progression-free survival was seen in younger patients with bevacizumab, it was not evident in older patients with bevacizumab. In conclusion, these analyses did not find a clear survival advantage of bevacizumab in older patients. Although adverse events were not consistently worse in older patients, the questionable efficacy of this drug in middle-aged and older patients suggests that healthcare providers should be more cautious when prescribing this drug for older NSCLC patients. In contrast, the epidermal growth factor receptor (EGFR) inhibitor erlotinib improves survival in older patients, but with more adverse events. To our knowledge, no prospective trials have been conducted in elderly patients, but some trials, such as the EURTAC (European Tarceva Versus Chemotherapy Comparative Randomized Trial) trial, have studied cohorts of elderly (median age 65 years) patients. This trial studied patients with EGFR mutated tumors and showed that progression-free survival was longer with erlotinib compared to chemotherapy. A trial of unknown age in which patients were not selected for mutation status, the BR.21 study, showed that erlotinib improved progression-free survival as a second- or third-line agent, but was more costly in older patients. In this older patient cohort, 112 patients were treated with erlotinib and 51 with placebo. Although progression-free survival, overall survival and tumor response rates were similar in older and younger patients, older patients had more severe toxic effects such as rash, malaise and dehydration. In fact, adverse events were more frequent and more severe (grade 3 and 4) in older patients (35%:18%; P=.001). The aforementioned toxic reactions led to early discontinuation of erlotinib. Therefore, erlotinib plays an important role in the treatment of elderly patients with NSCLC, especially those with EGFR-mutated tumors. However, before prescribing erlotinib, a discussion of its realistic adverse effects should be conducted. Adjuvant chemotherapy The standard treatment for patients with stage IB-IIIA (high-risk) NSCLC of unknown age is four courses of postoperative cisplatin-based combination chemotherapy. A series of large randomized phase III clinical trials have demonstrated improved overall survival. To our knowledge, there are no prospective trials specifically investigating the use of adjuvant chemotherapy in elderly patients. Cisplatin is cleared by the kidneys and is sometimes less well tolerated by elderly patients, but it can be a key agent. reanalysis by Pepe et al. The JBR.10 trial investigated adjuvant cisplatin and vincristine. The study was conducted in 482 patients with surgically resected non-small cell lung cancer. 155 patients were 65 years and older, and chemotherapy prolonged their overall survival (HR = 0.61, 95% CI, 0.38 – 0.98; P = .04). Adverse events, including hospitalization and chemotherapy-related death, did not differ between groups. Older patients received smaller amounts of cisplatin than younger patients: 49% received fewer than 5 doses, 19% 5-7 doses, and 32% 8 doses. These results suggest that cisplatin-based adjuvant chemotherapy is beneficial for older patients, although dose issues may need to be ignored or dose adjustments may be required. The LACE (adjuvant cisplatin for lung cancer evaluation) meta-analysis reviewed all 5 cisplatin trials with a total of 4584 patients; the study reported a 5.4% gain in 5-year overall survival. Twenty percent of the patients in this comprehensive analysis were 65 years of age or older, and 9% were 70 years of age or older. Although the number of older patients was limited, there was an age-based analysis of LACE data. The study divided patients into three age groups: younger than 65 years, 65-70 years, and older than 70 years. There was no major age difference in HRs for death, (Ptrend= .29). Rates of serious toxic reactions were similar between groups. Older patients received smaller doses of cisplatin. Finally, mortality was higher in older patients due to non-cancer related causes. These data suggest that adjuvant cisplatin chemotherapy is beneficial in selected elderly patients even at lower total doses. In addition, several researchers have used databases to study the effects of cisplatin-based adjuvant chemotherapy in the elderly. Using the Surveillance, Epidemiology and End Results (SEER) database, Wisnivesky et al. reported on 3324 patients over 65 years of age. All patients had received surgery for stage II or stage IIIA non-small cell lung cancer. Only 21% of the patients received platinum-based chemotherapy. Notably, this number does not reflect current treatment rates because this study spanned a long interval when adjuvant chemotherapy was not the standard of care. overall survival benefit improved in patients treated with stage II or IIIA chemotherapy (HR, 0.78). The improvement in survival was seen mainly in patients younger than 70 years (HR, 0.74, 95% CI, 0.62-0.88) and 70-79 years (HR, 0.82; 95% CI, 0.71-0.94). no survival benefit was seen in patients older than 80 years (HR, 1.33; 95% CI, 0.86-2.06). As expected, adjuvant chemotherapy increased the likelihood of serious adverse events (OR, 2.0; 95% CI, 1.5-2.6). This study suggests that adjuvant chemotherapy should be considered in older lung cancer patients (but not necessarily in their 80s). Similarly, Cuffe et al. reported 6304 patients with surgically treated NSCLC, comparing chemotherapy in each age group (under 70, 70-74,75-79, and 80+ years). It was assumed that hospitalization rates within 6-24 weeks of surgery would reflect chemotherapy-related toxicity. In summary, 2763 of 6304 surgical patients (44%) were over 70 years of age. The proportion of adjuvant chemotherapy in this age group increased from 3.3% (2001-2003) to 16.2% (2004-2006). Of the older patients evaluated, 70% were treated with cisplatin and 28% with carboplatin-based regimens. Rates of dose adjustment or drug substitution were similar in all age groups. Hospitalization rates within 6-24 weeks of surgery were also similar (28% of patients under 70 years of age and 27.8% of patients 70 years and older; P=0.54). Importantly, 4-year survival increased over time in older patients (47.1% of patients in 2001-2003 and 49.9% in 2004-2006, P=.01;). Survival improved in all but elderly patients over 80 years of age. This study also supports adjuvant chemotherapy in older patients under 80 years of age. Finally, the Veterans Administration cancer registry reported 10,036 surgically resected patients, of whom 3,958 (39.4%) were older than 70 years of age, 11.2% of older patients and 22.3% of younger patients received adjuvant chemotherapy. A small proportion of the chemotherapy patients received cisplatin-based therapy in older patients (86.4%: 91.8%, P = .001). Phase II as well as III elderly patients receiving cisplatin-based adjuvant chemotherapy had better 3-year overall survival rates than those receiving carboplatin-based adjuvant chemotherapy or no adjuvant chemotherapy (55% v 42% v 35%, respectively; P = .01). Similarly, cisplatin-based adjuvant chemotherapy appears to be beneficial for older patients with non-small cell lung cancer. In conclusion 1. cisplatin-based adjuvant chemotherapy is appropriate for relatively healthy elderly patients with non-small cell lung cancer. 2. adjuvant chemotherapy has not been found to be beneficial for patients over 80 years of age. It should be used with extreme caution.3. Although carboplatin-based chemotherapy is presumed to be inferior to cisplatin-based adjuvant chemotherapy, carboplatin-based chemotherapy still has some benefit. However, the lack of prospective data to confirm this last point suggests that it should be used with extra caution by physicians.