Small Cell Lung Cancer•Case •Small cell lung cancer •Presentation •Risk factors •Treatment •Future •Summary •Comments and questions Objectives •By the end of this

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Small Cell Lung CancerJoel Michalski MD PHD

Medical Oncology

Nebraska Cancer Specialists

Disclosures

• Grant/Research Support: NA

• Speaker’s Bureau: NA

• Consultant: NA

• Major Shareholder: NA

• Other: NA

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Outline

• Objectives

• Case

• Small cell lung cancer

• Presentation

• Risk factors

• Treatment

• Future

• Summary

• Comments and questions

Objectives

• By the end of this discussion, the audience will

• Be able to appreciate the major risk features for small cell lung cancer (SCLC)

• Understand the presentation of (SCLC)

• Appreciate the multi-speciality collaboration required to adequately treat SCLC

• Understand the current state of systemic therapy for SCLC

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Let’s start with a case…

• 60-ish white male

• Presented to urgent care 3 times with left arm weakness and pain

• Contact 1: MSK injury->symptomatic care

• Contact 2: 1 week later: referral to PT

• Contact 3: 1 week later: noticed pupil asymmetry -> ED





• Contact 2; 1 week later: referral to PT

• Contact 3; 1 week later: noticed pupil asymmetry -> ED

• ED->concern for stroke->brain MRI and CTA head and neck

• No stroke, but large infiltrative mass invading the left brachial plexus

• Onc consult:

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• Onc consult: Exam: Large chest wall mass, nicotine patch









• Onc consult: Large chest wall mass, nicotine patch

• Biopsy->SCLC

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SCLC: Epidemiology

Incidence 200k/year New cases 2019: ~30,000

SCLC: Epidemiology

1970’s

~25%

2000’s

~50%

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SCLC: Epidemiology

1970’s 2000’s

~25% ~50%

Clinical Presentation

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Clinical Presentation

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Staging: body imaging

• Brain MRI

• Combined staging system

• AJCC TNM system

• VA Lung Study Groups 2-stage system:

Staging: body imaging

• Brain MRI


• AJCC TNM system

• VA Lung Study Groups 2-stage system:• Limited Stage

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Staging:

• Brain MRI


• AJCC TNM system


Staging:

• Brain MRI


• AJCC TNM system


• Extensive Stage

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Treatment

• Regardless of stage, systemic therapy plays a role

• Multi-speciality evaluation

• Limited stage: Mediastinal LN eval negative

• Surgery candidate: T1-2 with pN0->lobectomy

• pN0 confirmed->systemic therapy

• pN1/2->RT plus systemic therapy

• Poor surgical candidate:

• SABR->systemic therapy or,

• Concurrent systemic therapy and RT

Treatment

• Regardless of stage, systemic therapy plays a role

• Multispeciality evaluation

• Limited stage: Mediastinal LN eval Positive

• T3-T4, N0; or T1-4, N1-3: systemic therapy + RT

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Systemic therapy

CisplatinEtoposide

1980’s 2006-7 2018

Irinotecan/Cis?Topotecan

Immunotherapy

At least 40 phase III clinical trials, largely negative

Immunotherapy and SCLC

• Mixed results, in general…

• ES-SCLC, front line: IMPOWER-133 trial:

https://www.lungcancernews.org/2019/02/26/impower133-finally-moving-the-needle-in-sclc/

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NEJM 12/6/2018; 379:2220-2229

NEJM 12/6/2018; 379:2220-2229

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• ES-SCLC, front line: IMPOWER-133 trial: Positive

• ES-SCLC, frontline: NCT01450761

954 pts 1:1-Chemo-Chemo+Ipi




• ES-SCLC, frontline: NCT01450761: Negative

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• ES-SCLC, pembrolizumab maintenance: negative (phase II)






• ES-SCLC, CASPIAN Trial: Positive

• EP

• EP+durvalumab followed by 1 year of durvalumab

• EP+durvalumab+tremelimumab+durvalumab followed by 1 year of durvalumab

• OS improved (mOS 13.0 months in DEP vs 10.3 mos in the EP)

• Tremelimumab data is not mature

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• ES-SCLC, CASPIAN Trial: Positive

• ES-SCLC, ipi+nivo maintenance: CheckMate-451: Negative (phase III, unpublished)

On the horizon…

• Immunotherapy:

• PD-1 inhibitor: 12 trials

• PD-L1 inhibitor: 6 trials

• CTLA-4+PD-1/L1 inhibitors: 7 trials

• Other (CD47, JAK1, etc): 5 trials

• Cell cycle modulators/inhibitors: 6 trials

• Stem cell pathways: 6 trials

• Epigenetics: 3 trials

• DNA damage repair: 8 trials

• Others: 13 trials

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Case update

• Patient was staged

• T4: extensive soft tissue involvement, 8cm mass with mediastinal invasion

• M1a: separate pleural nodule in the same hemithorax

• AJCC=IVa

• VA-LSG=Extensive stage

• Started on Carboplatin, Etoposide, atezolizumab per IMPOWER 133

• Palliative RT to brachial plexus

• Presented for Cycle 2:

• Horner’s syndrome: stable

• Pain: improved

• Weakness: stable

• Chest wall mass: barely appreciable

• Constitutional: increasing wt, more active

Summary

• SCLC is

• Rare: 10-15% of lung cancers

• Aggressive:

• Two thirds of pts have extra-thoracic disease at diagnosis

• Median OS is ~10-12 months from diagnosis

• Associated with several paraneoplastic syndromes

• Heavily investigated, with frustrating resistance to many classes of therapeutics

• 40 years of research->5 new drugs approved (pembrolizumab, atezolizumab, nivolumab+/- ipilimumab, topotecan)

• Systemic therapy is indicated in all circumstances

• Chemotherapy is the backbone of systemic therapy; platinum+etoposide

• Immunotherapy has a role in relapse and upfront; marginal benefit

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Thanks for your attention!

• Questions?

Documents

Small Cell Lung Cancer•Case •Small cell lung cancer •Presentation •Risk factors •Treatment •Future •Summary •Comments and questions Objectives •By the end of this