NSCLC

1. Manegment Of Non Small Cell
Carcinoma
DR KIRAN

3. • Level 1 : Supra clavicular, low cervical, sternal notch
• Superior Mediastinal : Upper(2) and lower para tracheal (4)
Retrotracheal (3p), Pre vascular (3a)
• Aortic : Sub aortic (5) , para aortic (6)
• Inferior Mediastinal : Sub carinal (7)
Para esophageal(8)
Pulmonary Ligament (9)
• N1 : Hilar (10) Interlobar (11)
Lobar (12), Segmental (13)
Subsegmental (14)

5. Modalities for treatment
• Surgery
• Radiation
• Chemotherapy

6. Management of Stage I/II

7. Surgery
• RESECTABLE LESIONS – STAGE I, STAGE II, STAGE III A
• Patient selection is critical in this scenario .
• PFT evaluation should include determination of lung volumes
and flow rates and of diffusing capacity and arterial blood gas
analysis.
• Imaging studies also includes Ventilation perfusion studies to
determine regional variation in pulmonary function.

8. Surgery : Types
• Radical operation:
– Pneumonectomy.
• Lung Conservation:
– Lobectomy.
– Sleeve resection.
– Wedge resection.
– Segmentectomy.
• Mediastinal lymph node dissection:
– Provides complete nodal staging.
– Identifies patients who require adjuvant
radiotherapy.
– Improves survival.
– Improves local control.
• At least nodal sampling should be
performed, if not complete
lymphadenectomy.

9. Thoracoscopic Lobectomy::
• Video-assisted thoracoscopic surgery (VATS) or thoracoscopic
lobectomy is a minimally invasive surgical treatment currently
being investigated in all aspects of lung cancer.
• Has several advantages over standard thoracotomy:
- Acute and chronic pain is minimal.
- Associated with low post-operative morbidity and mortality.
- Minimal risk of intra-operative bleeding.
- Minimal loco-regional recurrence.
- More rapid return to function than lobectomy by thoracotomy.

10. Lymph node dissection
• Lobe specific mediastinal nodal
dissection in NSCLC:
– Right Side:
• Upper lobe (1,2,3,4,7)
• Middle lobe (1,2,3,4,7)
• Lower lobe (1,2,3,4,7,8,9)
– Left Side:
• Upper lobe (4,5,6,7)
• Lower lobe (4,5,67,8,9)

11. • Complete surgical resection is free resection margin,
systematic node dissection on sampling, and highest
mediastina node negative tumour.
• Role of surgery in Stage IIIA (N2) is controversial. Presence or
absence of N2 should be vigorously investigated before
choosing modality of treatment.
• Martini et al survival in clinical N2 after surgery was 8% at
3yrs.
• Van Meerbeeck et al EORTC phase III randomised trial surgical
resection vs RT after induction chemo with cisplatin in
pathological proven N2, showed RT was better.

12. Criteria for inoperability
• Tumor based criteria:
– Cytologically positive effusions.
– Vertebral body invasion.
– Invasion or in casement of great vessels.
– Extensive involvement of Carina or trachea.
– Recurrent laryngeal nerve paralysis.
– Extensive mediastinal lymph node metastasis.
– Extensive N2 or any N3 disease.

13. Results
• T1 tumors:
– Five-year overall survival:
82%.
– 10 year overall survival: 74%.
• T2 tumors:
– Five-year overall survival:
68%.
– 10 year overall survival: 60%
• Morbidity:
– 15% reduction in spirometric
values in lobectomy
– 35% - 45% reduction after
pneumonectomy.
• Mortality:
– 7% perioperative mortality
for pneumonectomy.
– 4% perioperative mortality
for lobectomy

14. Patterns of failure
• In stage I tumors:
– Local recurrence rate = 7%
– Distant failure rate = 20%
– Second primary cancer = 34%
Martini et al, J Thor Cardiov Surg 1995; 109: 95 – 110.
• In stage II / III tumors:
– Intrathoracic failure rate: 31%
Ludwig lung cancer study group. Ann Surg 1987; 250: 67 –
71.
– 5 survival in clinical N2 negative nodes: 27%
– 5 survival in clinical N2 positive nodes : 8%
Martin et al. Ann Surg 1983; 198 (3): 386 – 97.
– Tumors measuring 1-2 cm have a mediastinal nodal metastasis rate of 17% as
compared to those measuring 2 to 3 cm, when the rate is 37%!
• Patients who fail after surgery, present with extrathoracic disease 70% of
the time, local recurrence in 20% and local and distant metastasis in 10%.
• 2nd primary lung cancers are known to occur at a rate of 1% per year in
survivors.

15. Radiation

16. Results: Stage I with Conventional doses
Authors Dose % T1 3 yr OS 3 yr CSS
Intercurrent
death
Kaskowitz et al 63 Gy (Median) 38% 19% 33% 27%
Krol et al 60 – 65 Gy 47% 31% 42% 34%
Sandler et al 60 Gy (Median) 32% 17% 22% 16%
Sibley et al 64 Gy (Median) 54% 24% - 43%
Talton et al 60 Gy 3% 21% - -
Noordijk et al 60 Gy 50% 33% - 40%
• Comparison for crude survival data presented by Fletcher et al
reveals the 3 year survival rate of 10% in less advanced tumors.
• Presently patients with T1 tumors can expect a 3 yr actuarial
survival probability in the range of 20% - 30%.

17. Patterns of failure: Early stage
• Definitive RT alone results in local failure in 33% -
45% patients.
• Lower doses (40Gy) result in local failure in 44% -
50% patients.
• LeChevalier et al have reported 83% -85%
pathological local failure rates in patients treated
with dose of 65 Gy.
• Incidence of distant mets 75% -80%
• Local tumor control however yields a significantly
better survival (22%) at 3 yrs as compared to local
failure (10%).

18. Better Surgical results: Why?
• As a curative modality radiotherapy fares poorly in studies as:
– Most patients excluded from surgical series have serious
medical comorbidities.
– Pathological staging is not done  37% upstaging by
pathological staging can be the reason for stage wise
better survival in lung cancer in surgical series.
– Both modalities are for local control and surgery results in
quicker and more through eradication of a small localised
disease.
– Consideration of long term and short term toxicity result in
the inability to deliver an actual curative dose in RT trials.
– The mobility of these tumors may be another reason for
their apparent poorer result.

19. Role of Radiotherapy
• RT can be applied in the following settings:
– With curative intent
– With Palliative intent
• RT is the most common treatment modality in majority of
patients in India as:
– Majority of the patients present with hilar or mediastinal
disease.
– Disease bulk prevents the use of surgical techniques.
– Surgical oncology facilities are not available widely.
– Associated comorbidities and poor lung function make
patients not suitable for surgery.
– Advanced age and poor socioeconomic status make RT an
attractive treatment option.

20. Objectives For Radiation
• Radiation is used for
– definitive treatment alone (or with chemotherapy).
– adjuvant treatment post surgery.
• Treatment for relief of symptoms, when the disease is too
locoregionally advanced for control.
• Treatment in special situations:
– Treatment for superior sulcus tumors.
– Treatment for SVCO.
– Local palliative treatment
– Brachytherapy.

21. Dose Escalation
• Fletcher predicted that using conventional fractions of size
1.8-2Gy, doses of 100Gy or higher might be required for
sterilization of most tumours.
• This suggests that escalation of the biologic effective dose (by
increasing the total dose or decreasing overall time with an
increased fraction size or multiple fractions per day) to a small
target volume.
• Hence use of Sterotactic Body Radiation Technique or Stero
Abalative Radiotherapy was indroduced.

22. SABR
• SABR has achieved comparable results in terms od OS, tumour
control comparable to that of lobectomy , and higher results
than with traditional 3DCRT , in medically inoperable and
older patients. Crabtree et al , Grill et al.
• Can be used in tumours upto size 5cm.
• Arbitrarily fractions < 5 is termed as SABR.
• Timmerman et al RTOG 0236 :
OS at 3yrs was 56.8% , Median OS 48.1 months,
Local tumour control 90.6%. , distant faiure at 22%

23. • SBRT systems can either use a frame-based system or it
can be frameless.
• Frame-based systems have been developed to control
lung and tumor motion, including compression devices,
breath-hold techniques, automated breathing control or
full body moulds.
• For frameless systems, gold fiducial markers can be
placed to allow tumor localization by the treatment
machine, or stereotactic real-time imaging can be
performed to localize the tumor visually prior to
treatment.
• Stereotactic methods of tumor localization decrease the
effects of lung and tumor motion, resulting in smaller
treatment fields and margins.

24. • Commonly used doses for
SABR:
Total dose No. of
fractions
Indications
25-34Gy 1 Peripheral, small (<2cm) tumors,
esp. >1cm from the chest wall
45-60Gy 3 Peripheral tumors and >1cm from
the chest wall
48-50Gy 4 Central or peripheral tumors <4-
5cm, esp. <1cm from chest wall.
50-55Gy 5 Central or peripheral tumors, esp.
<1cm from chest wall.
60-70Gy 8-10 Central tumors.

25. Limitation of SBRT
• Motion due to respiration presents a complicating factor.
• This is unacceptable for stereotactic large-fraction treatment.
A number of approaches have been developed for minimizing
respiratory motion :
 Breath-hold and abdominal compression techniques,
 gating the beam-on time to a particular phase of the
respiratory cycle also called frame based.
 tracking the tumor or radiopaque fiducial markers implanted
in it and adapting the target volume to the real-time position
of the tumor also called frameless.

26. • Because patients are at risk for a second primary or
mediastinal relapse, close follow-up is required. Imaging
should be obtained at least 2-3 months after completion of
SBRT.
• Serial PET scans are not recommended as inflammation can
persist for as long as 6 months to 2 years.
• Thus SBRT, with its advantage of patient convenience and
promising local control results, has largely replaced
conventionally fractionated radiotherapy as the standard
approach in the medically inoperable patient.

27. • At expense of potential risk of radiation pneumonitis

28. • Two international phase III trials for SBRT are underway-
- The Stereotactic Radiotherapy versus Surgery (STARS) Trial,
which compares surgery vs. Cyberknife SRT for stage I
NSCLC;
- The Radiosurgery or Surgery for Operable Early-Stage NSCLC
(ROSEL) study, which compares local control, QOL and
treatment costs of surgery versus SBRT.

29. Postoperative Radiotherapy
• Indications:
– Advanced disease:
• Margin positive (< 0.5 cm)
• Microscopic or macroscopic residual disease
• Hilar or mediastinal node positivity
• Mediastinal or chest wall invasion.
• Why is data regarding PORT inadequate?
– Unlike surgical series none of the studies have taken into account the
extent and site of nodal involvement which have been found to be
important prognostic variables.
– Many studies reported used inadequate doses and improper
fractionation and were conducted in the orthovoltage era.

30. POST OP RT
• Loco-regional recurrences after is 20% for patients with stage I
disease while 50% stage III after rescection.
• Cause of failure is along surgical stump or mediastinal lymph
nodes.
• PORT meta analysis data was published by MRC showed
benefits for pN2 in 5 yr OS but reduced OS for pN0 and p N1.
• At present adjuvant PORT cannot be recommended on the
basis of demonstrably improved survival but should be
considered
in selected patients at high risk of local recurrence,
particularly when there is involvement of multiple nodal stations
or extracapsular tumor spread.

31. Post OP RT
• Additional support for use of PORT in modern era was
demostrated by ANITA trial.
• Trial included 840 patients (1994-2000) stages IB to IIIA to
adjuvant chemotherapy or observation, use of RT was not
randomised.
• RT doses was 45-60Gy were given after chemotherapy.
• Improved survival was seen in pN2 disease in both chemo arm
as well as observation arm.

33. Post op RT Fractions Duration
Negative margin 50-54@ 1.8-2Gy/fraction 5-6 weeks
Extra capsular node ext or
microscopic disease.
54-60@ 1.8-2Gy/ fraction 6 weeks
Gross residual tumour 60-70 @ 2Gy/fraction 6-7 weeks.

34. Stage III Non-Small Cell Lung Cancer::
• Majority of patients with inoperable locally advanced NSCLC
(stage IIIB) receive definitive thoracic RT as part of their
treatment strategy, with concurrent chemotherapy (standard of
care acc to RTOG 94-10 trial).
• Sequential chemoRT or RT alone is appropriate for frail patients
unable to tolerate concurrent therapy.
• Accelerated RT regimens may be beneficial ( to improve
therapeutic ratio and survival rates and to decrease local
failures)--- particularly if not concurrent with chemotherapy i.e.
in a sequential or RT-only approach.

35. Stage III Non-Small Cell Lung Cancer (contd.)
• Preoperative concurrent chemoRT is an option for patients
with resectable stage IIIA (minimal N2 and treatable with
lobectomy) and is also recommended for resectable superior
sulcus tumors.
• Preoperative chemotherapy and postoperative RT is an
alternative for patients with resectable stage IIIA.
• In patients with clinical stage I/II upstaged surgically to N2+,
PORT is generally administered after post-op chemotherapy.
For positive resected margins, PORT with concurrent
chemotherapy is recommended.

36. • stage III
Resectable Unresectable
Preop chemo or
chemoRT chemoRT RT only
surgery
PORT + adj. CT

37. Chemotherapy
• Based upon the premise that 70% - 80%
patients will have micro-metastasis during
presentation.
• Situations where CCT can be used:
Neoadjuvant CCT as an induction regimen
Adjuvant chemotherapy with or without radiation
Palliative chemotherapy in systemic disease.
• No advantage of consolidation chemotherapy
has been established.

38. CHEMORADIATION
• Chemotherapy and RT can be combined in several ways.
• One can try to achieve additive cytotoxicity by treating the
known local disease with RT and the local and systemic
disease with chemotherapy.
• This strategy may allow greater sparing of normal tissue by
virtue of smaller RT target volumes or lesser resections
performed of the postchemotherapy tumor volume.

39. Induction CCT-Preop Chemotherapy
• Induction CCT is a sometimes used in stage III A patients to make them suitable
for surgery  Downstaging is the intent of treatment.
• Disadvantage:
– Delay in initiation of radiotherapy if patient fails to respond to CCT
– Some patients otherwise suited for primary surgery may have disease progression
during CCT itself.
• Approach remains valid in a very small selected group of highly motivated and
affordable patients with good general condition preferably in a trial setting!
Author Regimen N RR Survival Median
Survival
Roth et al CEP x 3  Sx 28 35% 56% (3yr) 64 mo
Sx alone 32 - 15% (3yr) 11 mo
Rosell et al IPM x 3  Sx 30 30% 20% (3yr) 26 Mo
Sx alone 30 - 5%(3yr)- 8 mo

40. Pre OP Chemotherapy
• Betticher et al multicentre phase II trial in potentially
operable Stage III a (pN2)
• 3 cycles of cisplatin and docetaxel with subsequent surgical
resection.
• 31% downstaged to N0- mediastinal and hilar nodal
clearence.

41. Preop Chemo Radiation
• SWOG – phase II induction chemo-radiation with surgery in
stage III A/III B showed 3yr survival 35%.
• Phase III intergroup trial compared Concurent chemo
radiation with platin based regimen and radiotherapy upto
45Gy ----- surgery if no progression vs
radiotherapy till 61Gy
• OS median survival was 23.6months in trimodality arm and
22.2 months in bimodality arm (p=0.24) .
• Trial showed no added benefits for trimodality treatment.

42. Chemotherapy regimens for NACT and adjuvant therapy::
• Cisplatin 50mg/m2 days 1 and 8; vinorelbine 25mg/m2 days 1, 8,
15, 22, every 28 days for 4 cycles.
• Cisplatin 100mg/m2 day 1 ; vinorelbine 30mg/m2 days 1, 8, 15,
22, every 28 days for 4 cycles.
• Cisplatin 100mg/m2 day 1; etoposide 100mg/m2 days 1-3, every
28 days for 4 cycles.
• Cisplatin 75mg/m2 day 1; gemcitabine 1250mg/m2 days 1 and 8,
every 21 days for 4 cycles.

43. • Cisplatin 75mg/m2 day 1; docetaxel 75mg/m2 day 1 every 21
days for 4 cycles.
• Cisplatin 75mg/m2 day 1; pemetrexed 500mg/m2 day 1 for
adenocarcinoma and large cell carcinoma and NSCLC NOS
(without specific histologic subtype) every 21 days for 4 cycles.
• For patients with comorbidities or patients not able to tolerate
cisplatin---- paclitaxel 200mg/m2 day 1, carboplatin AUC 6
day 1, every 21 days.

44. Sequential CCT +RT : Results
Author Regimen N Median Survival 3 yr OS
Dilman et al
(CALGB)
RT (60) 77 9.7 mo 11%
PV  RT (60) 79 13.8 mo 23%
Sause et al
(RTOG 88-08)
RT (60) 149 11.4 mo 6%
PV  RT (60) 151 13.2 mo 15%
RT (69.6) 152 12 mo 13%
LeChevalier RT (65) 177 10 4%
VCPC  RT  VCPC 176 12 12%
• A metaanalysis by the Institut Gustave-Roussy and the British Medical Research
Council Cancer Trials Office showed a statistically significant, overall benefit
with chemotherapy.
• The overall hazard ratio (HR) was 0.90 (p = 0.006)
• The absolute survival benefit was 3 per cent at 2 years and 2 per cent at
5 years!

45. • Sequential chemoRT regimens:
- Cisplatin 100mg/m2 days 1 and 29; vinblastine 5mg/m2/weekly on
days 1,8, 15, 22, 29; followed by RT.
- Paclitaxel 200mg/m2 over 3hours on day 1; carboplatin AUC 6 over
60 minutes on day 1 every 3 weeks for 2 cycles followed bt RT.
- Concurrent chemoRT followed by chemotherapy:
- Paclitaxel 45-50mg/m2 weekly; carboplatin AUC 2 with RT f/b 2
cycles of paclitaxel 200mg/m2 and carboplatin AUC 6.
- Cisplatin 50mg/m2 days 1, 8, 29, 36; etoposide 50mg/m2 days 1-5,
29-33 with RT f/b cisplatin 50mg/m2 and etoposide 50mg/m2 x 2
cycles (category 2B).

46. Concurrent Vs Sequential RT
• Furuse et al [MVP +RT vs Sequential CT RT
5yr OS 15.8% vs 8.9% , MS 16.5 mo vs 13.3]
• RTOG 9410 : cisplatin + vinblastin + conevntional RT
cisplatin + oral etopside + hyperfractionated RT
sequential CT with convention fravtionation
• Fournel et al
• Auperin et al

47. Selection of Concurrent Regimen
• In fit patients concurrent CT RT with platinum based regimen
used – Cis platin 50mg/m2 days 1 and 8 , 29, 36. along with
Etopside 50mg/m2 iv on day 1-5 , 19 thru 33 along with RT
60Gy/30.
• Persons with co morbidities Pacli/Carboplatin can be used.
• Carboplatin (AUC 2 weekly) + Palclitaxel 45-50mg/m2 during
RT followed by 2 cycles of Consolidative chemotherapy with
the same.
• Patients with border line PF, induction chemotherapy
followerd bt RT alone or CTRT.

48. Toxicity
• Combined modality is associated with increased risks of acute
esophagitis, on a long term pulmonary fibrosis and
pneumonitis.
• Three fold increase risk of grade III or worse esophagitis in
concurrent CTRT vs sequential CT RT.

49. Dose and Fractionation with RT alone
• RTOG 7301 established 60Gy as standard of care in inoperable
NSCLC.
• 365 patients non operable status randomized to 4 regimens
• 40Gy given in spilit course of 20Gy
• 40Gy , 50Gy, 60 Gy given at 2 dose per fraction continous 5
days a week.
• Incidence for tumor recurrence was least in 60 Gy arm at 35%
although the no difference in 5 yr survival rates. Between 4
arms.

50. Dose Escalation
• Basic data: (Fletcher et al) Dose required for eradication of
malignant squamous cell lung cancer encountered usually
varies from 80 – 100 Gy.
• RTOG 8311 dose of 1.2Gy twice daily escalated from starting
point of 60Gy to 79.2Gy
• 69.6Gy dose had improved survival among lower doses, no
observed survival differences in three high dose arms.

51. Continued.
• North Central Cancer Treatment Group also conducted similar
study,
• 3 arm study -regimen of 1.5 Gy given twice daily for 20
fractions over 2 weeks, a 2-week break, and another 1.5 Gy
given in 20 fractions
Vs conventional 60Gy in 30 fractions over 6 weeks
Vs twice-daily split-course regimen with concomitant
cisplatin plus etoposide chemotherapy.
• In the North Central Cancer Treatment Group (NCCTG) trial,
freedom from local progression was better for the twice-daily
regimen with or without concomitant chemotherapy,
although this did not quite reach statistical significance

52. Accelerated Fractionization
• CHART is a variant where 54 Gy were delivered in 1.5 Gy / # thrice
daily over 12 continuous days. Inter-fraction interval 6 hrs inclusive
of weeknd.
• Modification HART whr interfraction interval was 4 hours, weeknd
ommited
• Results:
– 2 year survival 29% (Control – 20%)
– Local control 23% (Control – 15%)
– Acute radiation pneumonitis 10% (Control 19%)
– Severe esophagitis 19% (Control 3%)
– Late pulmonary fibrosis requiring treatment 16% (Control 4%)
Saunders et al. Radiotherapy and Oncology 1999;52:137-148
• New modality : CHARTWEL

53. Accelerated Fractionization with
Chemo
• ECOG conducted a trial of HART compared with
standard daily fractionation in patients with stage IIIA
and IIIB NSCLC.
• Patients received two cycles of induction
chemotherapy with carboplatin and paclitaxel and
were then randomized to conventional RT or HART.
• The results, a median survival of 21 months on the
HART arm and 13 months on the standard arm.
• But the difference did not reach statistical significance.

54. Dose escalation with Chemotherapy
• RTOG 0617 , conducted 2x2 trial with 60Gy vs 74Gy and
concurrent CT with or without cituximab
• Concluded 60Gy arm was superior, although intrim analysis
(i)did not identify patient concerns
(ii) gave no indication of stastical difference in high grade
toxicity between both arms
(iii)nor any clear explaination for observed decrement in
survival.

56. Stage IV
• PALLIATIVE RT
• SITES: thorax, bone, brain
• Doses: 20Gy/5, 30Gy/10 or 17Gy/2 or 10Gy in single fraction
• Brain : SBRT+/- WBRT
• Bone : 8Gy in single fraction, bisphosphonates.
• This suggests that for patients with widely metastatic disease
and good performance status, an initial trial of chemotherapy
should be offered, with RT reserved for nonresponding
lesions.
• RT should used early in patients with metastases to weight-
bearing bones, impending spinal cord compression, or caval
or major airway obstruction.

57. WBRT AND RADIOSURGERY
• Severe brain edema and compressive symptoms relieved by
surgical decompression.
• WBRT is standard of management for brain mets, but side
effects fatigue and somnolence and permanent neuro-
cognitive deficits as late complication..
• Solitary lesion –surgery +/- WBRT. Patchel et al.
• One to three brain metastases may be treated with
radiosurgery alone, WBRT, or both in combination. RTOG9508.
• The clear and consistent result was that neurocognitive
function was significantly better when WBRT was withheld.

58. WBRT & Radiosurgery
• In patients with poor PS or extensive
extracranial disease, WBRT is appropriately
the treatment of choice.
• In patients with more than five brain
metastases, good PS, and limited extracranial
disease, the role of WBRT versus stereotactic
radiosurgery is illdefined.

59. • Doses:
Palliative RT Total dose Fraction size Treatment
duration
Obstructive
disease
30-45Gy 3Gy 2-3 weeks
Bone mets with
soft tissue mass
20-30Gy 4-3Gy 1-2 weeks
Bone mets
without soft
tissue mass
8-30Gy 8-3Gy 1 day-2 weeks
Brain mets 30Gy 3Gy 2 weeks
Any mets in
patients with
poor PS
8-20Gy 8-4Gy 1 day-1 week

60. Palliative Chemo Therapy
• Chemotherapy is the mainstay of treatment for patients who
present with stage IV disease at diagnosis or who experience
recurrent disease that is not amenable to local therapy.
• Median survival of approximately 10 to 12 months for
patients with nonsquamous histology, and 9 to 10 months for
squamous carcinoma.
• The respective 1-year survival rates are 20% to 25% and 15%
to 20%.

62. First Line Chemo Agents
• Platinum based chemo regimens
• Combined with Docetaxel, Paclitaxel, gemcitabine,
vinorelbine, irinotecan, and etoposide. Nab-Paclitaxel
• Decisions regarding which agent to use are based on the
toxicity profile, ease and convenience of administration, and
cost.
• The general standard is to administer four to six cycles of
chemotherapy unless progression or toxicity prevents this.
• Biological agent can be added and continued till progression
of disease.

63. PS vs AGE
• PS of 02, results in more complications,
however combined chemo regimen has shown
benefits with respect to symptom reduction.
• PS 03 and less not candidates for
chemotherapy.
• AGE > 70, similar profile to PS 02. Carboplatin
is prefered.
• Age > 80 must be proceeded with caution.

64. Histology & Choice of Agents
• Pemetrexed has no efficacy in squamous cell
carcinomas and should not be used in these
patients.
• Bevacizumab, an antiangiogenesis inhibitor,
has a high rate of bleeding complications in
squamous cell carcinomas and should not be
used in these patients.

65. Maintenance Regimen
• Continuation of chemotherapy more than4-6 cycles has no
benefits
• At this juncture stragedy is to treat at progression of disease
or to pursue maintenance regimen.
• Continuation maintenance means that the nonplatinum agent
used in the initial regimen is continued until disease
progression. OR
• switch maintenance in which a new agent, one not used in
the initial regimen, is initiated after the initial regimen.

67. Second Line Chemo Agents
• Cytotoxic agents used in this setting include docetaxel and
pemetrexed.
• Gemcitabine is also used in previously treated patients.
• Efficacy is similar among the chemotherapy agents, but
toxicity profiles are somewhat different.
• EGFR Tyrosine Kinase have also shown benefit in this setting.
• Second-line chemotherapy is preferred for EGFR wild-type
patients; erlotinib or gefitinib is usually used in these patients
only after two lines of chemotherapy.

68. Third Line Chemo Agents
• Erlotinib only drug approved for third line
agent.
• The ACCP and NCCN guidelines recommend
third-line treatment with erlotinib over basic
supportive care in good PS patients.

69. Targeted Therapies

71. Targeted Therapy
• Drugs that target tumor blood vessel growth:
Bevacizumab (Avastin), Ramucirumab (Cyramza)
• Drugs that target cells with EGFR changes:
(a) Erlotinib (Tarceva) Afatinib (Gilotrif) Gefitinib
(b) EGFR +T790M mutation : Osimertinib
(c) EGFR in squamous cell NSCLC : Necitumumab
• Drugs that target cells with ALK gene changes:
Crizotinib (Xalkori) Ceritinib (Zykadia) Alectinib

73. Immuno Therapy
• Immunotherapy is the use of medicines to stimulate a
person’s own immune system to recognize and destroy
cancer cells more effectively.
• An important part of the immune system is its ability to
keep itself from attacking normal cells in the body.
• To do this, it uses “checkpoints” – molecules on
immune cells that need to be turned on (or off) to start
an immune response.
• Cancer cells sometimes use these checkpoints to avoid
being attacked by the immune system. But newer
drugs that target these checkpoints hold a lot of
promise as cancer treatments.

74. Immuno therapy
• Nivolumab (Opdivo) and pembrolizumab (Keytruda) target
PD-1, a protein on immune system cells called T cellsthat
normally helps keep these cells from attacking other cells in
the body.
• By blocking PD-1, these drugs boost the immune response
against cancer cells. This can shrink some tumors or slow their
growth.
• These drugs can be used in people with certain types of
NSCLC whose cancer starts growing again after chemotherapy
or other drug treatments.
• These drugs are given as an intravenous (IV) infusion every 2
or 3 weeks.