NcXHF

BEYOND SECOND-LINE TREATMENT FOR LUNG CANCER
no strong evidence supporting the clinical value of further
anticancer treatment.
• Studies show that cancer-directed treatments are likely
to be ineffective for solid tumor patients who meet the
above stated criteria.
• Exceptions include patients with functional limitations due
to other conditions resulting in a low performance status or
those with disease characteristics (e.g., mutations) that suggest
a high likelihood of response to therapy.
• Implementation of this approach should be accompanied
with appropriate palliative and supportive care.”
And in the 2013 List of Recommendations:
• “Do not use a targeted therapy intended for use against a
specifıc genetic aberration unless a patient’s tumor cells
have a specifıc biomarker that predicts an effective response
to the targeted therapy.”
While the ASCO Clinical Practice Guidelines (2011 Focused
Update) do not explicitly discourage the further treatment
of lung cancer after patients have progressed on fırstand
second-line therapies, the guidelines stop short of recommending
against third- and fourth-line therapy:
• “When disease progresses on or after second-line chemotherapy,
treatment with erlotinib may be recommended as
third-line therapy for patients with performance status of 0
to 3 who have not received prior erlotinib or gefıtinib.
• Data are not suffıcient to make a recommendation for or
against using cytotoxic drug as third-line therapy; patients
should consider experimental treatment, clinical
trials, and best supportive care.”
CONCLUSION
After years of slow progress, the speed of innovation in advanced
NSCLC has increased greatly, with an explosion of
new therapies, targeted therapies, and immunotherapies. Although
these new options offer great promise for patients,
they may also paradoxically increase the risk of ineffective
and potentially harmful treatment near the end of life. When
there is general pessimism about the role of treatment in
advanced lung cancer, it is less likely to be given, either appropriately
or inappropriately. As enthusiasm grows for
treatment, practicing oncologist struggles to provide those
treatments to patients in a way that maximizes potential benefıt
and minimizes risk. This is a diffıcult dilemma given the
absence of randomized data in the third- and fourth-line settings.
However, the available data suggests some principles:
• Every patient with advanced NSCLC should receive early
palliative care and advance care planning with regard to
end-of-life care. This will reduce the risk of futile and
unwanted treatments, has been shown to improve outcomes,
and empowers patients to make informed decisions
about their care.
• Routine use of cytotoxic chemotherapy in the third and
fourth line is not supported by prospective data. Patients
with previous response to therapy and continuing
good performance status seem most likely to
benefıt from further lines of therapy.
• For patients with NSCLC, molecular analysis is a necessary
component of care and may identify treatment options
even after conventional second-line therapy.
The therapy options for patients with NSCLC have greatly expanded.
These therapies have improved the overall survival and
quality of life of many patients affected by the disease. Their high
cost is a challenge to patients, physicians, and society in general.
Medical oncologists have the responsibility to gather all evidence
to identify therapies likely to benefıt and protect patients
from the toxicities of ineffective therapies.
Disclosures of Potential Conflicts of Interest
Relationships are considered self-held and compensated unless otherwise noted. Relationships marked “L” indicate leadership positions. Relationships marked “I” are those held by an immediate
family member; those marked “B” are held by the author and an immediate family member. Institutional relationships are marked “Inst.” Relationships marked “U” are uncompensated.
Employment: None. Leadership Position: None. Stock or Other Ownership Interests: Craig H. Reynolds, Gilead Sciences. Honoraria: Craig H. Reynolds,
Boehringer Ingelheim, Celgene, Genentech, Lilly. Gregory J. Riely, Celgene. Consulting or Advisory Role: Craig H. Reynolds, Boehringer Ingelheim,
Genentech. Gregory J. Riely, ARIAD, Mersana, Novartis, Roche. Speakers’ Bureau: Craig H. Reynolds, Boehringer Ingelheim, Celgene, Genentech, Lilly.
Research Funding: Renato Martins, Astex Therapeutics (Inst), Bayer (Inst), Bristol-Myers Squibb (Inst), Celgene (Inst), Eisai (Inst), Eli Lilly (Inst), Genentech
(Inst), GlaxoSmithKline (Inst), Novartis (Inst), OSI Pharmaceuticals (Inst), Pfizer (Inst), VentiRx (Inst). Gregory J. Riely, GSK (Inst), Infinity (Inst), Millennium
(Inst), Novartis (Inst), Pfizer (Inst), Roche/Genentech (Inst). Patents, Royalties, or Other Intellectual Property: None. Expert Testimony: None. Travel,
Accommodations, Expenses: Craig H. Reynolds, Lilly. Gregory J. Riely, Novartis. Other Relationships: None.
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3. Ettinger DS, Wood DE, Akerley W, et al. Non-small cell lung cancer,
version 1.2015. J Natl Compr Canc Netw. 2014;12:1738-1761.
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