Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
comparing single agent vs. combination chemotherapy (5). The response
rate (38 versus 16 percent) and the median time to progression (4.6 versus
3.5 months) were statistically superior with combination chemotherapy.
Overall survival trended in the same direction, but the difference was not
significant (8.0 versus 6.6 months). Toxicity, as expected, was higher with
combination chemotherapy. The question of single agent vs combination
chemotherapy was addressed in a definitive manner by a phase III randomized
trial that compared pemetrexed alone or in combination with carboplatin
in 205 eligible patients with PS 2 (6). Respectively, the response rates were
10% vs 24%; the median progression free survival was 2.8 vs. 5.8 months;
and the median survival was 5.3 vs. 9.3 months, all statistically significant in
favor of the combination regimen. Toxicity was manageable but 4 treatmentrelated
deaths were observed in the combination arm. This trial has set a
new standard for treatment of advanced NSCLC patients with a PS of 2.
The advent of targeted agents led to the exploration of these agents as a
“gentler approach” to PS 2 patients, irrespective of the presence or absence
of the mutation. In a phase II randomized trial, patients were assigned to
either erlotinib or a combination of carboplatin and paclitaxel (7). Patients
treated with erlotinib had a significantly shorter median survival compared
to chemotherapy (6.5 vs 9.7 months, HR 1.73, 95% CI 1.09-2.73). As shown
in other trials, EGFR inhibitors should not be given to untreated patients
without the mutation, regardless of the PS. Guidelines from the American
Society of Clinical Oncology (ASCO) state that the data for patients with
PS 2 are insufficient to make a strong recommendation for combination
chemotherapy, and single agent therapy may be appropriate if the perception
of risk outweighs the perception of benefits (8). The European Society of
Medical Oncology (ESMO), after reviewing the same body of data, came up
with a straightforward recommendation for carboplatin-based combinations
to all eligible PS 2 patients (9). The National Comprehensive Cancer Network
(NCCN) merged PS 2 patients into the PS 0-1 group for recommendations
regarding first line therapy, with no obvious distinction between the
subsets (10). This progressive approach recognizes the advances made in the
management of PS 2 patients in the past decade and extends the benefits of
systemic therapy to a large group of patients who were, until recently, offered
inferior treatments.References:
Lilenbaum RC, Cashy J, Hensing TA, et al. Prevalence of poor performance
status in lung cancer patients: implications for research. J Thorac Oncol 2008;
3:125
Sweeney CJ, Zhu J, Sandler AB, et al. Outcome of patients with a performance
status of 2 in Eastern Cooperative Oncology Group Study E1594: a Phase II
trial in patients with metastatic nonsmall cell lung carcinoma . Cancer 2001;
92:2639
Langer CJ, O’Byrne KJ, Socinski MA, et al. Phase III trial comparing paclitaxel
poliglumex (CT-2103, PPX) in combination with carboplatin versus
standard paclitaxel and carboplatin in the treatment of PS 2 patients with
chemotherapy-naïve advanced non-small cell lung cancer. J Thorac Oncol
2008; 3:623
O’Brien ME, Socinski MA, Popovich AY, et al. Randomized phase III trial
comparing single-agent paclitaxel Poliglumex (CT-2103, PPX) with singleagent
gemcitabine or vinorelbine for the treatment of PS 2 patients with
chemotherapy-naïve advanced non-small cell lung cancer. J Thorac Oncol
2008; 3:728
Lilenbaum R, Villaflor VM, Langer C, et al. Single-agent versus combination
chemotherapy in patients with advanced non-small cell lung cancer and a
performance status of 2: prognostic factors and treatment selection based
on two large randomized clinical trials. J Thorac Oncol 2009; 4:869
Zukin M, Barrios CH, Pereira JR, et al. Randomized Phase III trial of singleagent
pemetrexed versus carboplatin and pemetrexed in patients with
advanced non-small cell lung cancer and Eastern Coopertaive Group
performance status of 2. J Clin Oncol 2013; 31:2849–2853
Lilenbaum R, Axerold R, Thomas S, et al. Randomized Phase II Trial of Erlotinib
or Standard Chemotherapy in patients with Advanced Non-Small Cell Lung
Cancer and a Performance Status of 2. J Clin Oncol 2008; 26:863-869
Masters GA, Temin S, Azzoli G, et al. Systemic therapy for stage IV nonsmall
cell lung cancer: American society of clinical oncology clinical practice
guideline update. J Clin Oncol 2015; 62:1342
Reck M, Popat S, Reinmuth N, et al. Metastatic non-small cell lung cancer
(NSCLC): ESMO clinical practice guidelines for diagnosis, treatment, and
follow-up. Ann Oncol 2014; 25 (suppl 3): iii27
National Comprehensive Cancer Network. Non-Small Cell Lung cancer
(Version 4.2016). http://www.nccn.org/professionals/physician_gls/pdf/
bone.pdf. Accessed September 15, 2016
Keywords: Advanced NSCLC PS 2
SESSION MTE28: IMPLEMENTATION OF PRECISION MEDI-
CINE IN ROUTINE PRACTICE: THE LATIN AMERICAN EXPE-
RIENCE (TICKETED SESSION)
WEDNESDAY, DECEMBER 7, 2016 - 07:30-08:30
MTE28.01 IMPLEMENTATION OF PRECISION MEDICINE IN ROUTINE
PRACTICE: THE LATIN AMERICAN EXPERIENCE
Mercedes Dalurzo
Pathology, Hospital Italiano de Buenos Aires, Ciudad Autonoma de Buenos Aires/
Argentina
Technology for molecular testing in lung cancer is a highly demanding aspect
to tackle in the LATAM countries. Molecular testing requires incorporation
of new technologies usually involving expensive equipment, reagents
and supplies. Moreover, these items are commonly imported from other
countries and are subjected to custom regulation and heavy taxes. Therefore,
LATAM labs commonly face unpredictable delays in the legal processing of
purchase orders, are constantly adjusting to changes in regulations and in
the country’s financial status, and suffer from slow and sometimes poor
support from companies that do not see them as preferred clients. As an
example of consequences of some of this points, in Argentina the agents
Nivolumab and Pembrolizumab were approved by government agencies
for immunotherapy for NSCLC before the molecular testing laboratories
had conditions to purchase the DAKO platform and the CDx antibodies for
appropriate IHC testing. Some technical devices such as automated IHC
platforms are more widely available. They were initially integrated onto large
pathology labs in the main cities of several countries but smaller automated
platforms are currently available in a number of other cities. There are
laboratories equipped for fluorescence in situ hybridization (FISH) and for
DNA sequencing in most countries. Sanger sequencing is still commonly used,
but the main laboratories already incorporated newer technologies such
as RT-PCR allele-specific technology (usually Cobas platform) and tailored
panels of next generation sequencing (NGS) or have them in the short list
for implementation. Additionally to the challenges in the laboratories
organization, two other main issues obstruct the implementation of lung
cancer molecular testing in the LATAM countries: the lack of a stable logistic
infra-structure necessary to ship biological samples to the molecular
laboratories in a cheap, reliable and rapid way, and the hurdle of cost
reimbursement for the tests. In the past 10 years, expenses and logistics
for transfer of biological specimens and reimbursement for molecular
test costs, in most countries such as Mexico, Brazil and Argentina, were
sponsored by pharmaceutical companies. Companies such as AstraZeneca,
Roche, Boehringer Ingelheim, and Pfizer have acted through clinical trials
or special access programs. In a smaller scale, molecular tests have been
supported by governmental health agencies or covered by private health
care insurance companies. A restricted number of patients are paying the
tests out of the pocket, mostly sending to US laboratories. Least but not
least, the implementation of lung cancer molecular testing relies in the
adequate quantity and, most importantly, in the good quality of the available
biological sample. Subsequent to the intense interdisciplinary work by the
laboratory personnel, significant progress has been detected in the last years
in the amount of tumor cells present in the testing specimens. However,
proper quality is only achieved in a fraction of specimens. Most LATAM
countries do not have local regulations for quality control (QC) of pathology
laboratories, and a limited number of those laboratories are taken external
QC certification. Moreover, there is no financial support for the adequate
validation of the assays at their implementation and for the competency
checking periodically thereafter. In consequence, the risk of having
laboratories testing in substandard quality conditions is high. Institutions
that are well-structured administratively, technically and scientifically
and that handle large volumes of clinical specimens usually participate
in external QC for molecular tests. They engage in accredited proficiency
testing activities or, at least, send material to reference laboratories for
investigation of reproducibility of results. Unfortunately, this does not occur
in the majority of the LATAM laboratories. Therefore, it is critical to reach
potential sponsors to assist the LATAM molecular testing laboratories in
overcoming these challenges and rapidly jump to the future. Efforts leading
to improve tissue quality, to facilitate local optimization of assays and to
ensure assay validation by international standards are needed. A group of
regional laboratories have been trying to organize a collaborative project to
face these issues and also to come up with an affordable strategy to ensure
good quality in pathology and molecular laboratories. Multiple barriers are
making it difficult to succeed in this effort. The patient advocate groups have
proved effective in sensitizing governments and regulatory agencies in the
USA, but those groups are still very under-represented in LATAM. Professional
institutions such as the IASLC are specially tailored to help. IASLC congregates
internationally conscious personnel and lung cancer experts and would
excel, for instance, in matching experts with laboratories requesting
specific assistance and in coordinating a regional consortium of laboratories
interested in rounds of specimen exchange for proficiency testing and
in validated sets of control specimens for implementation of new tests.
S92 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017