Case Studies in Non- Small Cell Lung Cancer 2018 GPO Case Study Day

Transcription

1 Case Studies in Nn- Small Cell Lung Cancer 2018 GPO Case Study Day Dr. Steve Kulla GPO, Nanaim Cancer Clinic Dr. Gergia Geller Medical Onclgist, Vancuver Island Center

2 Dr. Steve Kulla Nne Disclsures Dr. Gergia Geller Nne

3 Briefly review: Learning Objectives Basic Canadian statistics n nn-small cell lung cancer Diagnsis and staging f nn-small cell lung cancer Discuss treatments fr nn-small cell lung cancer including surgery and raditherapy, but in particular systemic treatments including: Chemtherapy Targeted therapies Immuntherapy

4 Lung Cancer sme basic statistics Canadian Cancer Sciety Canadian Cancer Statistics: A 2018 special reprt (cancer.ca/statistics) Lung cancer was the mst cmmnly diagnsed cancer amng Canadians in 2017 (14% f all cancers) Smking remains the mst imprtant risk factr 85% f cases are related t smking The incidence rate fr lung cancer is higher fr males than females (althugh sex-specific rates amng yunger adults appear t be cnverging) Differences in incidence rates between males and females reflect past differences in tbacc use (in females, the drp in smking ccurred ~20yrs later than it did in males)

5 Lung Cancer sme basic statistics Canadian Cancer Sciety Canadian Cancer Statistics: A 2018 special reprt (cancer.ca/statistics) Frm , every year in Canada (excluding Quebec), an average f 6823 lung and brnchus, 2494 clrectal, 815 female breast, and 1187 prstate cancers were diagnsed after they had metastasized (stage IV) Abut half (50%) f all lung cancers were diagnsed at stage IV, which is reflected in its lw five-year net survival f 17% 5 year net survival fr breast cancer = 87% 5 year net survival fr clrectal cancer = 64% 5 year net survival fr prstate cancer = 95%

6 Lung Cancer Sme basic statistics BC Cancer Website - Overall, lung cancer causes abut 25.5% f all cancer deaths in British Clumbia (greater than clrectal, breast, and prstate cancer cmbined) Mean age f diagnsis is 70 years ld The median verall survival is abut 8.5 mnths

7 Lung Cancer Sme basic statistics

8 Lung Cancer Basics 2 main types f lung cancer: Nn-small cell lung cancer (NSCLC) Small cell lung cancer (SCLC) NSCLC accunts fr >80% f all lung cancers ~40% f NSCLC cases are adencarcinma subtypes ~40% f NSCLC cases are squamus tumrs Remaining NSCLC cases are large cell carcinma and adensquamus carcinma SCLC is rare amng nn-smkers. It tends t grw faster and spread mre easily than NSCLC

9 Lung cancer screening Currently there is n ppulatin based screening fr lung cancer The Canadian Task Frce n Preventative Health Care has released screening recmmendatins fr high-risk individuals using lw-dse CT Pilt studies are underway CXR and sputum cytlgy are nt effective screening tests

10 Case #1 Mrs. O 61F widw (husband died f lung cancer), frmer teacher and scial wrker, n children hx f cln cancer 2017 Initially presented with anemia and psitive FIT Clnscpy July 2017 Resectin Sept 2017 Fund t be stage II, lw risk, and thus n chemtherapy at that time Otherwise healthy, n regular medicatins Never smked. Hx f secnd-hand smke expsure frm her mther As part f wrkup fr cln cancer, LUL mass incidentally discvered n staging CT

11 What wuld yu recmmend fr wrkup f the LUL mass?

12 What wuld yu recmmend fr wrkup f Histry: the LUL mass? Recvered quite well frm her cln cancer surgery N significant weight lss, n fevers/sweats, n hemptysis Sme pst-intubatin harseness and cugh Dry cugh, exacerbated by activity Minr shrtness f breath n exertin N headaches, visin changes, r neurlgical deficits Physical exam: Unremarkable n lymphadenpathy, chest clear, n adventitia Bldwrk: WBC 8.8 (ANC 5.8), Hgb 119, plt 342, creat 67, albumin 45, liver enzymes nrmal, LDH 167, CEA 1.0

13 What wuld yu recmmend fr wrkup f the LUL mass? Imaging: Private PET (Aug. 2017) The left hypermetablic left upper lbe lung lesin atypical fr metastasis and may be a secnd primary malignancy PFT s (Nv. 2017) Nrmal FEV1 and FVC Brnchscpies & bipsies (Oct & Nv. 2017) Bipsies negative Left upper lbe lbectmy (Nv. 2017) Nn small cell lung cancer (pulmnary adencarcinma), pt2 N2 (2/4 LN psitive), fcal lymphvascular invasin, margins clear, tumr was intermediate grade Further Imaging: CT Head (Dec 2017) n intracranial mass r enhancing lesin

14 TNM staging fr NSCLC T, N, M descriptrs fr the 8 th editin f TMN classificatin fr lung cancer - UpTDate T1 Tumr 3cm, surrunded by lung r visceral pleura, withut invasin mre prximal than lbar brnchus T2 Tumr >3cm but 5cm, r tumr with any f the fllwing features: Invlves main brnchus, withut invlvement f the carina Invades visceral pleura Assciated with atelectasis r bstructive pneumnitis T3 Tumr >5cm but 7cm r any f the fllwing Directly invades any f the fllwing: chest wall, phrenic nerve, parietal pericardium Separate tumr ndules in the same lbe T4 Tumr >7cm r invades the diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esphagus, vertebral bdy, carina with separate tumr ndules in a different ipsilateral lbe

15 TNM staging fr NSCLC T, N, and M descriptrs fr the 8 th editin f TMN classificatin fr lung cancer UpTDate NX reginal LNs cannt be assessed N0 n reginal LN metastases N1 Metastasis in ipsilateral peribrnchial and/r ipsilateral hilar LNs and intrapulmnary ndes, including invlvement by direct extensin N2 Metastasis in ipsilateral mediastinal and/r subcarinal LN(s) N3 Metastasis in cntralateral mediastinal, cntralateral hilar, ipsilateral r cntralateral scalene, r supraclavicular LN(s)

16 TNM staging fr NSCLC MX presence f distant metastasis cannt be assessed M0 n knwn distant metastasis M1 Distant metastasis present

17 TNM staging fr NSCLC Stage I T1,2 N0 M0 Stage II T1,2,3 N1 M0 Stage III T1,2,3,4 N1,2,3 M0 Stage IV Any T Any N M1 **This is a simplified verview

18 Investigatins fr staging CXRs alne are inadequate fr staging Cntrast CT f mediastinum recmmended t stage lcreginal disease (it shuld extend inferirly t include the liver and adrenal glands) Majr rle f CT is t aid in decisins regarding resectability and t detect synchrnus/metastatic cancers nt visible n CXR MRI is nt superir t CT fr staging mediastinal ndes but may be f value in selected cases fr assessment f perability f the primary tumr CT shuld be supplemented by mediastinscpy Fr patients with clinically perable NSCLC, bipsy is recmmended f mediastinal LNs fund n CT t be >1cm in shrtest transverse axis PET is mre sensitive and specific than CT in radilgic detectin f malignant LNs, yet there is a high false psitive rate. As a result, definitive bipsy wuld be recmmended. The rle f PET in rutine staging f lung cancer has nt been established, but it may be useful in select cases: Staging patients with clinical stage I lesins being treated with curative intent Staging f ptentially resectable stage II and III disease T aid in planning radical raditherapy Staging prir t resectin f slitary lung metastases

19 Assessment f Pleural Effusins If a pleural effusin is present, all effrts must be made t determine if it is malignant r benign. Useful investigatins include: Pleural fluid cytlgy Pleural bipsy Thracscpy A benign effusin has n independent significance in staging, whereas a malignant effusin indicates T4 status and inperability.

20 Screening fr Extrathracic Metastatic Disease The mst cmmn extrathracic metastatic sites fr lung cancer are: Supraclavicular ndes Brain Bne Adrenals Liver Histry, physical exam, and investigatins shuld fcus n these sites

21 Screening fr Extrathracic Metastatic Disease Serum chemistry: Include calcium, albumin, and LFTs Anrexia, nausea and vmiting, and ther GI symptms suggest hypercalcemia Alkaline phsphatase, LDH, AST help assess liver functin and pssible presence f liver metastases and bne metastases It is nt cmmn fr the liver t harbur detectable metastases in the absence f liver enzyme abnrmlities Bne scans are nt recmmended unless the patient has bne pain, chest pain, r elevatin f serum calcium and/r alkaline phsphatase The finding f an islated adrenal mass n US r CT requires bipsy t r/ metastatic disease if the patient is therwise cnsidered t be ptentially resectable (PET can be useful in select circumstances)

22 Screening fr Extrathracic Metastatic Disease Brain Metastases: There is a high incidence f detectable metastases in patients with specific neurlgic findings (fcal seizures, fcal weakness), and CT is advised in these patients There is a 25-35% incidence f detectable metastases in patients with nn-specific neurlgic cmplaints (headache, persnality change, dementia) CT brain screening is nt recmmended fr asymptmatic patients receiving treatment with palliative intent but such assessment shuld be cnsidered in lcally advanced cases where curative intent therapy is planned MRI is mre sensitive than CT, and shuld be cnsidered in cases where suspicin persists after nrmal r equivcal CT, r t delineate if there is a slitary lesin r multiple lesins which may affect surgical and radiatin planning.

23 Resectability? ~1/3 f NSCLC patients have clinically perable disease Fr patients with clinically perable NSCLC, surgical resectin is the treatment with the best ptential fr cure Patients with stage I r II NSCLC are rutinely resected Lbectmy is the standard Occasinally pneumnectmy required if extensin f tumr acrss the fissure Segmental r wedge resectin may be perfrmed fr small peripheral T1N0 lesins in patients with limited lung functin Only selected stage III patients are resectable Stage IV disease is generally unresectable Rarely, a carefully selected patient with a slitary brain metastasis and a stage I t II primary lung tumr will be cnsidered fr resectin Radical radiatin treatment may be cnsidered when the patient refuses surgery in therwise perable situatins, r when the patient is medically unfit fr thractmy

24 Adjuvant Radical Raditherapy after Surgery Pst-perative adjuvant raditherapy shuld nt be used after cmplete resectin f Stage I r II NSCLC due t an increased risk f nn-cancer deaths There is sme evidence that it can benefit patients with Stage III NSCLC after cmplete resectin It will decrease the chance f lcal recurrence in patients with psitive brnchial resectin margins

25 Case 1 Overview Mrs. O is a 61 year ld widw with resected stage III nn-small cell lung cancer (T2 N2 MX with 2/4 LN psitive)

26 Wuld yu recmmend systemic treatment fr Mrs. O?

27 Pst-perative Adjuvant Chemtherapy fr Resected NSCLC Platinum-based chemtherapy (ie, platinum dublet) regimens are recmmended as pstperative adjuvant therapy in patients with cmpletely resected stage II and III NSCLC Cisplatin-based treatment is preferred, but carbplatin-based regimen can be used if there is a cntraindicatin t cisplatin

28 Wuld yu recmmend systemic treatment fr Mrs. O? Mrs. O s esteemed Medical Onclgist recmmended that fr stage III patients, adjuvant cisplatin based chemtherapy had a 10-13% abslute benefit in 5 year survival. Mrs. O had a gd ECOG status Platinum dublet with cisplatin and vinrelbine was recmmended (4 cycles) Ideally it wuld be started within 8 weeks f her surgery

29 What txicities wuld yu cunsel Mrs. O t be aware f?

30 What txicities wuld yu cunsel Mrs. O t be aware f? Hypersensitivity reactin Fatigue Cytpenias Infectin (ptentially fatal febrile neutrpenia) Nausea/vmiting Neurpathy Nephrpathy Ottxicity VTE

31 Hw did Mrs. O tlerate treatment? Cycle 1: Tinnitus, n hearing lss Day 15 f cycle was held, and she was sent fr hearing test Hearing test shwed mderate t severe sensrineural hearing lss at high frequencies Switched t Carbplatin and Paclitaxel Nausea effectively managed with metclpramide Fatigue nt as active as nrmal, but ding ADLs and IADLs N neurpathy Cycle 2-4 well tlerated

32 Mrs. O cmpleted chem, nw what?

33 Mrs. O cmpleted chem, nw what? NSCLC patients treated with radical intent shuld be fllwed up fr treatment-related cmplicatins, detectin f treatable relapse, r ccurrence f secnd primary lung cancer At least 75% f relapses ccur in the initial 2-3 years after treatment. Suggest a fllw-up visit every 3-6 mnths fr the first 2-3 years fllwed by annual visits thereafter. Histry, physical exam, CXR and annual CT are apprpriate (as CT is the best way t detect a secnd primary tumr) Smking cessatin is f majr value in NSCLC patients (especially if treated with curative intent) decreased risk f mrtality, develpment f secnd primary r recurrence

34 Mrs. O cmpleted chem, nw what? Pst-chemtherapy CT C/A/P (April 2018): N evidence f metastatic disease within the abdmen and n new pulmnary findings In the right anterir aspect f the S2 segment f the sacrum there is a lytic lesin with peripherally sclertic margins, new frm previus imaging NM Bne scan lesin in S2 highly suspicius fr metastatic fcus

35 New bne lesin What des this mean fr Mrs. O? This is nw Stage IV disease her cancer is n lnger cnsidered curable

36 What further tests might yu cnsider at this pint?

37 What further tests might yu cnsider at this pint? Oncpanel: Lks fr driver mutatins fr which there may be targeted therapies, fr instance: EGFR ~10-35% f peple with NSCLC will have drug sensitizing mutatins f EGFR Peple with these mutatins tend t have adencarcinma histlgy and be light smkers r nnsmkers If EGFR mutatin (variant) psitive, can cnsider using Tyrsine kinase inhibitr such as erltinib, gefitinib, afatanib, r simertinib ALK ALK is psitive in 3-5% f NSCLC. The vast majrity f cases are adencarcinmas. ALK lung cancers are fund in all ages, but n average these patients tend t be yunger. They are mre cmmn in light smkers r nnsmkers If ALK psitive, can cnsider using ALK inhibitr such as criztinib, alectinib, r ceritinib PD-L1bimarker Utilized t assess fr utility f immune checkpint inhibitrs such as nivlumab r pembrlizumab

38 What further tests might yu cnsider at this pint? Oncpanel: EGFR psitive - variant f knwn functinal significance detected in exn 18, and secnd variant f pssible functinal significance in exn 20 ALK prtein negative PDL1 bimarker - <1% Repeat PET (May 2018): Slitary 2.5cm sseus sacral metastasis

39 What treatments wuld yu recmmend at this pint? She was reviewed at tumr bard, and she was felt t be a gd candidate fr the SABR5 clinical trial. She was advised that SABR culd ffer a high rate f lcal cntrl (80-90%), delay the develpment f ther metastatic disease, and delay systemic therapy As part f her wrkup fr SABR5, she received a brain MRI (June 2018): Multiple (at least 7) sub-centimeter lesins Due t the brain lesins, she was n lnger eligible fr the SABR5 trial.

40 Nw what? T review: 62F with ligmetastatic, EGFR mutated, ALK negative, adencarcinma f the lung with a single sacral metastasis, and new sub-centimeter brain mets. PDL1 < 1%. She s cmpletely asymptmatic frm the metastatic disease

41 Nw what? Her radiatin nclgist explained that the brain lesins were t small fr raditherapy, and did nt recmmend whle-brain raditherapy (**Mrs. O did nt want WBRT due t risk f cgnitive deficits). He referred her back t Medical Onclgy t discuss systemic therapy. Regarding the sacral lesin, as it was asymptmatic, Rad Onc recmmended n RT at that time, and re-referral fr palliative RT shuld she becme symptmatic frm it.

42 What systemic therapy ptins are available t Mrs. O?

43 What systemic therapy ptins are available fr Mrs. O EGFR targeted therapy: Afatinib a secnd generatin tyrsine kinase inhibitr TKIs, especially 3 rd generatin drugs have been shwn t have gd bld brain barrier penetratin Afatinib is a secnd-generatin tyrsine kinase inhibitr. It binds t the kinase dmains f EGFR, HER2 and HER4, irreversibly inhibiting tyrsine kinase autphsphrylatin, and results in reductin f tumur grwth and tumur regressin - BCCA Afatinib mngraph Gal f this therapy: This is a palliative medicatin given t cntrl her disease and hpefully maintain/imprve quality f life Median respnse quted t Mrs. O was 11mnths, with high rate f respnse (70%) She started Afatinib July 2018

44 Ptential txicities f Afatinib? EGFR TKI s are generally better tlerated than chemtherapy Typical side effects are: Dry skin Acneifrm rash (up t 90% f pts use tpical clinda/hc PRN +/- ral mincycline) Stmatitis Diarrhea (96% f pts use lperamide PRN) Parnychia (58% f pts) Rare but clinically imprtant pulmnary and hepatic txicity may als ccur *Cytpenias are nt cmmn

45 Hw did Mrs. O d n Afatinib? First week f full dse: 6 BM/d, respnded t lperamide Minr facial rash ECOG 0, gd energy, active Secnd week f full dse: Severe diarrhea (16BM/24hr), dehydratin necessitating visit t ER fr fluids Afatinib held until reslutin f symptms (this tk ~5d) Resumptin f Afatinib at a dse reductin well tlerated She tlerated dse reduced Afatinib well, and maintaned a gd QOL. She had a CT H/C/A/P n Oct. 3/18..

46 CT H/C/A/P result: Unfrtunately the CT Head shwed increase in size and number f intra-axial lesins, but n ther adverse changes. What d we d nw?

47 What d we d nw? She was referred t Radiatin Onclgy fr cnsideratin f steretactic brain raditherapy, and a brain MRI was rdered She cntinues Afatinib MRI shwed ~20 intracranial lesins, thus stertactic raditherapy n lnger an ptin (it generally cannt be given t >10 intracranial lesins) Mrs. O has an appintment with Rad Onc and Med Onc pending We had a very lng difficult discussin regarding gals f care: Rad Onc has advised that she recmmends all pts with intracerebral lesins stp driving. Driving ++ imprtant t Mrs. O. Mrs. O des nt want WBRT. She has ++ fear f cgnitive deficits. Mrs. O des nt want t wind up in hspital r require full care. She wuld cnsider MAID, but at present has full and happy life.

48 Case #2 Mrs. S 56F, married, previusly wrked as a care aid, but stpped due t shulder issues Chrnic bilateral shulder issues, multiple previus surgeries n R shulder, new L frzen shulder in summer f 2016 which did nt imprve with a crtisne injectin CT scan t investigate shulder shwed a mass in the L lung Otherwise healthy, n n regular medicatins, uses Advil PRN fr shulder pain 40 year smking histry

49 What wuld yu recmmend fr wrkup f the lung mass?

50 What wuld yu recmmend fr Histry: wrkup f the lung mass? Systemically well, with n SOB, cugh, r hemptysis N headaches, visual disturbances, seizures, r fcal neurlgical deficits Appetite is gd, weight stable Physical Exam: AVSS, chest clear n auscultatin, n supraclavicular LAN, nrmal neur exam Bldwrk: WBC 4.8, ANC 2.7, Hgb 136, Plt 206, Creat 59, Liver enzymes nrmal, Albumin 41, LDH 158

51 What wuld yu recmmend fr wrkup f the lung mass? Brnchscpy & bipsy: Pathlgy shws nn-small cell lung carcinma, favrs squamus cell carcinma Imaging: Bne scan (Sept 2016) n sseus mets PFTs: Nrmal Referred by Respirlgy t Thracic Surgery PET scan shwed L lung cancer with small ipsilateral ndes. Plan fr surgery. CT Head rdered fr further staging CT Head (Oct 2016): At least 8 hyperdense lesins in the cerebral hemispheres What wuld yu d nw?

52 Review: Case #2 - Mrs. S 56F with LUL mass fund incidentally n imaging. Cytlgy shws NSCLC. PET shws n distant disease. CT Head shws 8 mets. ECOG 0. Seen by Radiatin Onclgy (Nv 2016): Given knwn NSCLC, n bipsy f brain lesins recmmended Stage IV disease incurable, treatments will be palliative in nature Advised algrithm suggests median survival f 6-9 mnths Recmmended WBRT rather than steretactic apprach (30Gy in 10 fractins) Did nt recmmend RT t chest as Mrs. S was asymptmatic, as palliative chest RT nt shwn t imprve survival Advised by Rad Onc that she shuld nt drive given risk f seizures Referred t Medical Onclgy fr cnsideratin f systemic therapy

53 What are the ptential txicities f WBRT?

54 What are the ptential txicities f WBRT? Fatigue Skin reactin Alpecia Symptms f increased intracranial pressure Headache, nausea/vmiting, cnfusin Mrs. S. did nt have symptms at that time, s prphylactic dex was nt started, but Rad Onc advised that if symptms develped during r fllwing WBRT, dex wuld be cnsidered Lng term risk f reductin in memry

55 Medical Onclgy Assessment What treatments might Med Onc recmmend in the 1 st line setting fr Mrs. S?

56 Medical Onclgy Assessment What treatments might Med Onc recmmend in the 1 st line setting fr Mrs. S? Palliative Platinum dublet chemtherapy x 4 cycles Mrs. S. was prescribed carbplatin and gemcitabine What ther tests might be rdered at that visit?

57 Medical Onclgy Assessment What treatments might Med Onc recmmend in the 1 st line setting fr Mrs. S? Palliative Platinum dublet chemtherapy x 4 cycles Mrs. S. was prescribed carbplatin and gemcitabine What ther tests might be rdered at that visit? Oncpanel - Mlecular testing fr EGFR mutatins and ALK fusins N EGFR variant detected ALK negative PDL1 > 50%

58 Advanced NSCLC Treated with Palliative Intent Treatment gals are palliatin f symptms and imprvement in quality-f-life Prgnsis is pr fr patients with stage IV NSCLC with 6-10 mnth median survival times typical with even the best available therapies. Mst patients die within 1-2 years Palliative raditherapy may be given fr metastatic sseus, cerebral, subcutaneus, ndal, r pulmnary metastases

59 Advanced NSCLC Treated with Palliative Intent Examples where radiatin may be useful fr treatment f symptms due t direct extensin f lcal disease r invlvement f LNs: Atelectasis Obstructin f a main stem brnchus Superir vena cava syndrme Hemptysis Severe dysphagia Pain Examples where radiatin may be useful fr the treatment f symptms due t metastases: Bne metastases Spinal crd cmpressin Brain metastases Fungating cutaneus mass Radiatin may be cnsidered in asymptmatic patients if: Pending superir vena cava bstructin Ptential risk f spinal crd cmpressin Large lytic lesin in a weight-bearing bne Asymptmatic multiple brain metastases

60 Hw did Chem g fr Mrs. S? Tlerated it reasnably well CT t mnitr respnse after 2 cycles shwed slight decrease in size f chest lesin and L hilar LAN, n new pulmnary lesins, but fund t have a PE (asymptmatic) started n dalteparin. CT head shwed mixed change with decrease in a few lesins, but increase in size f thers. Cntinue treatment. Treatment related anemia after cycle 3 hgb 65, given 2U PRBC Platelets fell t 11 after cycle 4 dalteparin held until platelets > 50 Pst treatment CT (May 2017) shwed mixed results

61 What wuld yu recmmend fr Mrs. S nw? Review: 56F with metastatic NSCLC t brain. Status pst WBRT and 4 cycles f carbplatin and gemcitabine, which was cmplicated by a incidental PE, anemia, and thrmbcytpenia. Pst treatment CT shwed mixed respnse with n change n CT Head, slight increase in size f primary lung lesin. ECOG = 0.

62 What wuld yu recmmend fr Mrs. S nw? Review: 56F with metastatic NSCLC t brain. Status pst WBRT and 4 cycles f carbplatin and gemcitabine, which was cmplicated by a incidental PE, anemia, and thrmbcytpenia. Pst treatment CT shwed mixed respnse with n change n CT Head, slight increase in size f primary lung lesin. ECOG = 0. Immuntherapy!! Immune checkpint inhibitrs were funded at BC Cancer fr NSCLC starting March 2017 She was started n Nivlumab

63 Very brief intr t Immune Checkpint inhibitrs PD1 (prgrammed death 1) a prtein n T cells PDL1 (prgrammed death ligand 1) a prtein n the surface f healthy cells that suppresses T-cells (t help avid autimmunity) If a cell desn t have PDL1, the T-cell cnsiders it an abnrmal cell, and is activated Cancer cells can learn t express PDL1 t evade the immune system ( disguising themselves as healthy cells)

64 Very brief intr t Immune Checkpint inhibitrs Tumrs can essentially hide in plain sight frm the immune system using PD1/PDL1 Immune checkpint inhibitrs have been apprved t treat advanced cancers by taking away this ability They are mnclnal antibdies, but rather than targeting a specific prtein n cancer cells (like trastuzumab des with HER 2), they take the brakes ff the immune system

65 Why is it imprtant that frnt line prviders understand the difference between immune checkpint inhibitrs and chemtherapy?

66 Why is it imprtant that frnt line prviders understand the difference between immune checkpint inhibitrs and chemtherapy? They have unique txicities related t their mechanism f actin ie, immune-mediated txicities Chemtherapy interferes with cell cycle functin, thereby affecting rapidly dividing cells (bth cancer and nn-cancer cells which have a high turnver rate -> cytpenias, nausea, vmiting, diarrhea, neurpathies

67 Checkpint inhibitr txicity just add itis

68 They are generally well tlerated Surce: Weber JS, et al. The Onclgist 2016; 21:

69 Immune-related adverse events The cmmn: Fatigue, rash, pruritis, vitilig, diarrhea, hyper/hyp-thyridism The life-threatening: Pneumnitis, clitis, hepatitis, nephritis, Type I DM and DKA, pancreatitis, hypphysitis The unusual: Guillan-Barre syndrme, inflammatry mypathies, asceptic meningitis

70 Time t nset f immune mediated adverse events with Nivlumab (any grade, n=474) Surce: Webber J. Pled Analysis. Abstract ASCO 2015

71 Awareness and educatin are vital Mst immune-mediated adverse events are lw grade and easily managed, but early recgnitin is imprtant t prevent prgressin f txicity The crnerstne f treatment fr Grade 3-4 adverse events are systemic gluccrticids and withhlding (r permanent discntinuatin) f the immuntherapy

72 Back t Mrs. S Hw s she tlerating Nivlumab? After 4 cycles, she s tlerating it well, with n txicities. ECOG remains 0 CT t mnitr respnse shws slight increase in the size f the primary lesin What wuld yu recmmend?

73 Back t Mrs. S Hw s she tlerating Nivlumab? After 4 cycles, she s tlerating it well, with n txicities. ECOG remains 0 CT t mnitr respnse shws slight increase in the size f the primary lesin What wuld yu recmmend? Cntinue treatment

74 Pseudprgressin Be aware f pseudprgressin with immune checkpint inhibitrs Initial imaging can suggest tumrs have grwn, but this is the immune respnse Discvered in early trials when imaging shwed enlargement/prgressin f lesins. Pts had n ther ptins, and were tlerating tx reasnably well, s stayed n tx and imprvement was nted thereafter

75 Can immune checkpint inhibitrs crss the bld brain barrier?

76 Can immune checkpint inhibitrs crss the bld brain barrier? There is grwing evidence the immune checkpint inhibitrs can have psitive effect n sme brain metastases NSCLC, but early trials tended t exclude patients with brain mets, s mre data is needed.

77 What if Mrs. S s liver enzymes asymptmatically quadrupled?

78 What if Mrs. S s liver enzymes asymptmatically quadrupled? There is a lt f bldwrk that is mnitred during immuntherapy, with the gal f detecting txicities early, t prevent severe immune-mediated txicity CBC, creat, electrlytes, liver enzymes, TSH, mrning serum crtisl, lipase If her liver enzymes quadrupled the cncern wuld be an immune mediated hepatitis: Treatment shuld be held Medical Onclgy shuld be cntacted immediately Pt shuld be started n 1mg/kg prednisne

79 Mrs. S is ding well after 30 cycles f Nivlumab. What abut the dalteparin fr PE?

80 Mrs. S is ding well after 30 cycles f Nivlumab. What abut the dalteparin fr PE? The PE was asymptmatic, fund incidentally while n cyttxic chemtherapy, but was significant (partially cclusive RLL PE) She really wanted t stp LMWH injectins She saw a Hematlgist He advised that the PE was prvked by her cancer and chemtherapy He felt she required nging anticagulatin indefinitely He switched her t a DOAC (Rivarxaban) LMWH has been standard f care Data indicates DOAC can be used in certain situatins, but I recmmend seeing a Hematlgist t aid in this decisin as there s several imprtant factrs t cnsider (eg, GI tumrs have increased bleeding n DOAC cmpared t dalteparin, and there are als ptential drug interactins)

81 Hw s Mrs. S ding nw? Happy t reprt she s had 35 cycles f Nivlumab, and cntinues t d well. She has a CT and fllw up with her esteemed Med Onc pending this mnth.

82 Wrap up Nn small cell lung cancer is t cmmnly discvered in Stage IV Stage I, II, and sme III s can be resected with gal f cure Stage IV is incurable, and treatment is fcused n maintaining quality f life fr as lng as pssible, while minimizing the side effects f treatment Systemic therapies used in the adjuvant treatment after resectin in Stage II & III, and palliatively in Stage IV include: Platinum-dublet chemtherapy Traditinally the first-line systemic therapy, but algrithm is evlving Immuntherapy Immune-checkpint inhibitrs such as nivlumab r pembrlizumab Immune-checkpint inhibitrs are mving up the treatment algrithm, and are becming cmmn EGFR mutatin psitive: EGFR targeted tyrsine kinase inhibitrs such as afatinib, gefitinib, erltinib, and simertinib ALK fusin ncgene psitive: ALK targeted tyrsine kinase inhibitr such as criztinib, alectinib r ceritinib The different systemic therapies have unique ptential txicities that the GPO and frnt-line primary care physicians shuld be aware f.

83 Questins?