ASCO recently released updated guidelines on the use of adjuvant endocrine therapy in hormone-receptor-positive breast cancer. While the guidelines focus on all postmenopausal women, those who are age 75 and older require special consideration. Unfortunately, meaningful data to help healthcare providers make treatment decisions for these patients are scarce, according to Peter Ravdin, MD, PhD, an executive committee member and scientific program planning member of SABCS 2010.
Despite the fact that bevacizumab and cetuximab are both in an advanced stage of clinical development for use in treatment for unresectable NSCLC (with bevacizumab already licensed for the use in clinical practice), several unanswered questions regarding these drugs remain. A number of ongoing trials have been specifically addressed to answer them, however, the first priority should be to personalize treatment, through clinical or biological markers, in order to better select patients who could benefit from targeted therapy with decreased toxicity.
The review by Dr. Chiappori and colleagues in this issue of ONCOLOGY addresses an important challenge relating to the optimal management of elderly patients with lung cancer. The authors provide an excellent overview of the data in patients with various stages of non-small cell lung cancer (NSCLC). They also highlight the limitations of the existing data in the management of elderly NSCLC patients.
Calendar age and biological age do not always correspond. Pablo Picasso, source of the quote that begins the title of this commentary, lived a notoriously robust and active life through his later decades, dying in his nineties in the midst of a dinner party. In the oncology community, with the advent of targeted therapeutics and better supportive care, the disparity between the two is likely to be increasingly relevant to both research and practice. In this issue of ONCOLOGY, Chiappori et al review data supporting the idea that even in the context of standard cytotoxic chemotherapy, elderly patients with advanced NSCLC experience similar response rates and similar survival benefits to those seen in younger patients. They note that biases excluding elderly patients from clinical trials result in gaps in our knowledge of how to best treat older patients.
Despite the fact that elderly patients comprise over 50% of the non-small cell lung cancer (NSCLC) population, our knowledge regarding the efficacy and safety of chemotherapy in this group is suboptimal. The “elderly” (defined as individuals ≥70 years of age) experience physiologically normal aging of their bone marrow and kidneys, which inherently increases toxicity to therapy. Standard practice has often been to discourage the use of combination chemotherapy in these patients; however, general consensus guidelines emphasize that performance status should primarily guide the choice of treatment. Elderly patients with advanced NSCLC treated with platinum doublet therapy demonstrate similar efficacy (but increased toxicity) to their younger counterparts. Patients with metastatic disease in which a targeted and/or biological agent(s) was added to chemotherapy experienced benefits similar to those treated with standard platinum doublets, but with increased morbidity and mortality. In the future, effective testing of molecular targeted therapies will have to include elderly patients among research cohorts or risk excluding a large population of eligible patients. Overall, elderly patients with advanced NSCLC, while experiencing greater toxicity, demonstrate the same response rates and survival benefits as their younger peers.
The variety of treatment options available to patients of all ages who have multiple myeloma has improved considerably in the past decade. However, elderly patients have benefited more than patients of other ages. Because elderly patients, as a group, are usually not offered autologous stem cell transplant (ASCT) as a treatment option, they have been unable to benefit from the wide application of this technique, first introduced in the late 1980s. In the past 8 years, however, thalidomide, bortezomib, and very recently lenalidomide, when combined with conventional doses of alkylators and corticosteroids, have produced marked improvements in progression-free survival (PFS) and overall survival (OS) in elderly patients. Harousseau has thoroughly reviewed the important studies documenting these benefits for this population.
Until recently, standard treatment of multiple myeloma (MM) in elderly patients who were not candidates for autologous stem cell transplantation was with the combination of melphalan plus prednisone (MP). Novel agents (thalidomide, lenalidomide, bortezomib) are dramatically changing frontline therapy of MM. Randomized studies have shown the superiority of adding one novel agent to MP, either thalidomide (MPT) or bortezomib (MPV). The combination of lenalidomide with low doses of dexamethasone is another attractive alternative. Recent results show that maintenance therapy with low-dose lenalidomide may prolong progression-free survival. The objective of these improved treatment regimens should be to achieve complete response, as in younger patients. However, toxicity is a significant concern, and doses of thalidomide and of myelotoxic agents should be reduced in patients who are older than 75 years or who have poor performance status. Weekly bortezomib appears to induce severe peripheral neuropathy less frequently than the same agent administered twice weekly. Autologous stem cell transplantation is feasible in selected fit patients over 65 years of age, and its results are improved by the addition of novel agents before and after high-dose therapy. However, considering the progress in non-intensive therapy, autologous transplantation should not currently be offered to elderly patients outside of a clinical trial.
Doublet Chemo Proves Superior to Single-agent Therapy in Older Patients with Advanced Non-small-cell Lung Cancer
Data from French trial should inform treatment decisions in the majority of lung cancer patients aged 70 and up.
Osteoporosis in elderly cancer patients is an increasing problem, yet it remains under-recognized and under-managed. We commend Dr. Balducci for writing a comprehensive review of the bone complications associated with cancer and its treatment in the elderly.
Breast cancer is predominantly a disease of older women. Many of these older patients with breast cancer have low-risk disease owing to low proliferation indices, positive hormone receptors, node-negativity, or p53-negative and HER-2 (human epidermal growth factor 2)-negative tumors.[1,2] They do well without chemotherapy and will receive adjuvant hormonal therapy with tamoxifen or an aromatase inhibitor. Yet there are older women who do not have these favorable tumor characteristics and so are potential candidates for chemotherapy. The review by Muss points out this issue, highlighting benefits of chemotherapy and describing appropriate treatment regimens for these patients.