Assessing Physical Function and QOL in Doublet-Treated Elderly Lung Cancer Patients

Abstract & Commentary

By William B. Ershler, MD

Synopsis: In a trial of two platinum-based chemotherapy regimens for non-small-cell lung cancer in older patients, pretreatment assessment of physical function and quality of life predicted certain different adverse outcomes but neither treatment assignment was superior to the other with regard to improved "global" quality of life.

Source: Biesma B, et al, on behalf of the Dutch Chest Physician Study Group. Quality of life, geriatric assessment, and survival in elderly patients with non-small-cell lung cancer treated with carboplatin-gemcitabine or carboplatin-paclitaxel: NVALT-3 a phase III study. Ann Oncol 2011;22:1520-1527.

The majority of non-small-cell lung cancer (NSCLC) patients are older than age 70 years1 and identification of treatment goals for this group is important as the maintenance of quality of life (QoL) is most frequently desired. Although single-agent treatment often is recommended for elderly NSCLC patients,2-4 subset analysis from several platinum-based trials suggests similar efficacy in elder as younger patients without excessive toxicity.5,6 In this regard, the second drug might be of critical importance to clinical outcomes including QoL and physical function as well as survival. Previously, there had been no prospective randomized trials with platinum-based combination regimens in elderly NSCLC patients published.

To address this, Biesma and colleagues within the Dutch Chest Physician Study Group conducted a Phase 3 randomized clinical trial of two platinum-based drug regimens administered to elderly (70 years and older) NSCLC patients. A total of 181 chemotherapy-naive patients (performance score [PS] of 0–2) with stage III–IV NSCLC received carboplatin and gemcitabine (CG) (n = 90) or carboplatin and paclitaxel (CP) (n = 91) every 3 weeks for up to four cycles. Comprehensive geriatric assessment (CGA) and measurement of QoL were determined prior to treatment and components of these analyses were measured throughout the treatment program. Carboplatin was administered at an area under the concentration–time curve of 5 mg/ml/min on day 1 and either gemcitabine 1250 mg/m2 on days 1 and 8 or paclitaxel 175 mg/m2 on day 1. The primary endpoint was change in global QoL from baseline compared with week 18. A "QoL responder" was defined as a patient who had improvement of 10 points or more compared to baseline on the global QoL scale. Pretreatment CGA and mini-geriatric assessment during and after treatment were undertaken. A principal component analysis was carried out to determine the underlying dimensions of CGA and QoL that subsequently related to survival.

The number of QoL responders was small and there were no significant differences by treatment allocation (CG arm, 12%; CP arm, 5%). With regard to the comprehensive geriatric assessment, findings were only significantly associated with neuropsychiatric toxicity. Quality-adjusted survival was not different between treatment arms. The principal component analysis derived from nine CGA, six QoL, and one PS score indicated only one dominant dimension. This dimension was strongly prognostic, and physical and role functioning, Groningen Frailty Indicator, and Geriatric Depression Scale were its largest contributors. Global QoL scores were lower in patients with worse baseline PS scores. However, there were no associations between the global QoL and treatment, age, gender, pretreatment weight loss, or extent of disease. There also were no significant interactions between QoL scores and treatment.

With regard to components of the CGA, baseline deficits in emotional functioning (QLQ-C30), role functioning (QLQ-C30), or depression (GDS) scores were more likely to experience > grade 2 neuropsychiatric toxic effects. There were no significant interactions between CGA scores and treatment. Patients with better ADL, IADL, or physical functioning (QLQ-C30) scores were more likely to finish all chemotherapy cycles. Patients with worse emotional functioning (QLQ-C30), role functioning (QLQ-C30), or GDS scores were more likely to experience grade 2 or greater psychiatric toxic effects.

More myelosuppression and fatigue were observed in the CG arm. Grade 2 or greater neurological toxicity occurred more frequently in the CP than in the CG arm (neurosensory: 19% vs 5%, P = 0.002; neuromotor: 10% vs 2%, P = 0.03). In both arms, approximately 25% of the patients experienced grade 2 or greater neuropsychiatric toxicity. Alopecia grade 2 was observed in 7% and 37% of the patients in the CG and CP arms, respectively.

Commentary

This was the first report of its kind — a randomized trial focusing primarily on pretreatment comprehensive assessment and measures of QoL in the context of two effective chemotherapy regimens for NSCLC. The investigators are to be commended for the design and conduct of this trial and for the thorough analysis of complex data. For the practicing clinician, the findings are interesting but are not applicable yet to day-to-day practice. Further research needs to define those components of geriatric assessment that will prove useful in prescribing optimal treatment with as little impairment on QoL and physical function as possible.

From this report, we know paclitaxel or gemcitabine added to carboplatin did not have a differential effect on global QoL. Components of the CGA were associated with certain toxic effects but only in a very limited manner. In both treatment arms, patients with better physical functioning received more chemotherapy and survived longer.

References

1. Jemal A, et al. Cancer statistics, 2009. Cancer 2009;59:225-249.

2. Elderly Lung Cancer Vinorelbine Italian Study Group. Effects of vinorelbine on quality of life and survival of elderly patients with advanced non-small-cell lung cancer. The Elderly Lung Cancer Vinorelbine Italian Study Group. J Natl Cancer Inst 1999;91:66-72.

3. Gridelli C, et al. Chemotherapy for elderly patients with advanced non-small-cell lung cancer: The Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst 2003;95:362-372.

4. Pfister DG, et al. American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: Update 2003. J Clin Oncol 2004;22:330-353.

5. Langer CJ, et al. Cisplatin-based therapy for elderly patients with advanced non-small-cell lung cancer: Implications of Eastern Cooperative Oncology Group 5592, a randomized trial. J Natl Cancer Inst 2002;94:173-181.

6. Sederholm C, et al. Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: The Swedish Lung Cancer Study Group. J Clin Oncol 2005;23:8380-8388.