2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

OLDER PATIENTS WITH LUNG CANCER
Fig. 1. Analysis by age of survival comparing surgery with chemotherapy
to surgery alone (NSCLC) meta-analysis.
A meta-analysis has also been performed of individual
patient data comparing the effects of adding adjuvant chemotherapy
to surgery through the NSCLC Meta-analyses
Collaborative Group. 14 The first meta-analysis of surgery
plus chemotherapy compared with surgery alone includes 34
trials in 8,447 patients. The overall benefit of adding chemotherapy
after surgery was an absolute increase in survival
of 4% at 5 years with a hazard ratio of 0.86 (95% CI
0.81–0.92; p � 0.0001). Figure 1 demonstrates the hazard
ratio from that study. As shown, in all age subgroups, the
addition of chemotherapy to surgery improved survival, with
a trend for the greatest effect in the group older than age 70.
Although this is clearly a subset analysis and must be taken
with caution, it at least suggests that adjuvant chemotherapy
in older patients, who are appropriately selected, as they
would have been in these clinical trials, can provide survival
benefit at least comparable to that of younger patients.
Observational Studies of Adjuvant Chemotherapy in
the Older Population
How do these results from randomized clinical trials and
meta-analyses of these studies apply to clinical practice? An
observational cohort study utilizing the SEER registry and
Medicare database has been reported to address this question.
15 In this study, 3,324 patients older than age 65 were
identified as having surgery for stage II and IIIA NSCLC.
This included cases of lung cancer diagnosed up to 2005 with
follow-up data through December of 2007. The primary
endpoint was to look at overall survival. In this group of
patients, 21% received platinum-based chemotherapy.
There was improvement in overall survival for patients who
received chemotherapy, with a hazard ratio of 0.78. Beneficial
results were seen in both stage II and stage IIIA
patients. Within age strata, improved survival was seen in
the population younger than age 70 (HR 0.74, CI 0.62–0.88).
There was also improvement in overall survival for the
population age 70 to 79 (HR 0.82, CI 0.71–0.94). However,
no survival benefit was observed in the population older
than age 80 (HR 1.33, CI 0.86–2.06). The use of adjuvant
chemotherapy was associated with an increased odds ratio
of serious adverse events as determined by hospitalization
(OR 2.0, CI 1.5–2.6). Given the nature of this study, there
is no comparison population younger than age 65 and details
of exact toxicities are limited. This study extends the observations
from the clinical trial setting to clinical practice
regarding the potential benefit of adjuvant chemotherapy in
the elderly. Appropriate caveats also include that the benefit
of adjuvant chemotherapy is clearly not established in the
population older than age 80 and the effect of adverse events
must be also considered. Overall, there was 3.1% mortality
within 12 weeks of treatment for this population.
At the American Society of Clinical Oncology Annual
Meeting in 2011 (ASCO 2011), Cuffe and colleagues reported
on the patterns of use of adjuvant chemotherapy among
surgically resected patients with NSCLC in Ontario, with
the focus on the population of patients age 70 and older. 16
Although this represents more than 50% of the patients with
lung cancer, in JBR.10, only 15% of patients were older than
age 70, and the overall LACE analysis included only 9% of
patients in this age group. This study evaluated the use of
adjuvant chemotherapy and associated outcomes from 2001
to 2003, before results of JBR.10 and other clinical trials
demonstrating the benefit of adjuvant chemotherapy were
known. This “preadoption” time period was compared to the
“postadoption” time period of 2004 to 2006. The primary
study outcome was overall survival, with a secondary endpoint
of rate of hospitalization within six months of surgery
as a surrogate for toxicity. In this study, 6,570 patients were
identified who underwent surgical resection within 24 weeks
of diagnosis. Patients who received neoadjuvant radiation
and/or chemotherapy were excluded, leaving a population of
6,304 patients. In this group, 3,541 patients were younger
than age 70 with 1,217 patients age 70 to 74, 980 patients
age 75 to 79, and 466 patients older than age 80. Other
variables associated with survival differences included age
and Charlson comorbidity scores. The majority of chemotherapy
was delivered in the group younger than age 70.
Very few patients older than age 80 were treated with
chemotherapy. Overall survival by age group clearly favored
the population younger than age 70, with the worse survival
rate in the population older than age 80. However, when the
age groups were compared between the pre- and postadoption
time periods, improvement in survival was seen in both
the population younger than age 70 and older than age 70,
with hazard ratios of 0.85 and 0.87 respectively. By comparison,
no difference was seen in the population older than age
80, with a hazard ratio of 1.0. Toxicities, defined by hospitalization
within 6 weeks of surgery, were higher in the
population older than age 75 (p � 0.001) and ranged between
11% and 18%, reflecting postoperative complications.
By contrast, hospitalization rates between 6 and 24 weeks of
surgery, when a patient would have received chemotherapy,
were similar across all age groups and varied between 27%
and 32%. The authors suggest that there is an association
between the adoption of adjuvant chemotherapy in the older
population and the survival improvement, although the
majority of patients did not receive chemotherapy. The
benefit of adjuvant chemotherapy in patients older than age
80 was not clarified by this study, since so few patients
received treatment.
An additional study further explored the SEER Medicare
database to form a comparison between carboplatin- and
cisplatin-based regimens. 17 Although cisplatin-based chemotherapy
has been the standard recommended therapy in
the adjuvant setting, the older patient population may have
poor tolerance for this medication or be unable to receive it
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