NSCLC
Management - Advanced Disease
Non-Squamous
Histology Drives Rx Decisions
Molecular Drivers In Non Squamous NSCLC
BC Cancer Molecular Focus Panel
2022 Standard First Line therapy Paradigm
Management Algorithm: No driver mutation advanced NSCLC
First Line Chemotherapy Backbone Considerations
- Cisplatin favoured for young, fit patients
- Carboplatin has less GI and renal toxicity compared to Cisplatin and is favoured in older patients.
- Standard 3rd generation partners for platinum:
- Pemetrexed – 1 treatment every 21 days
- Paclitaxel – 1 treatment every 21 days (myalgia, atralgia and alopecia)
- Pembrolizumab
- Flat dose of 200mg every 3 weeks
Squamous
Algorithm
Dr. Cheryl Ho
EGFR Mutation
Overview
Management Algorithm
Exon 19 Deletion and L8585R
Uncommon EGFR Mutations
Toxicities of TKI's
- Generally well tolerated
- Most Common
- Skin rash (hydrocortisone 1% + clindamycin 2% in a Glaxalbase. Apply bid to affected areas
- Diarrhea (imodium–instead of reactive may take it regularly with the TKI)
- Paronychia –saline soaks, txbreak
- Rare, but significant
- Hepatotoxicity –monitor LFTs
- Pneumonitis -CXR
- Long Term
- Hair changes, nail changes, eyelash changes which can cause corneal irritation
Dr. Cheryl Ho
ALK Fusion
Overview
Drug mechanism of action
Treatment Algorithm
ALK Inhibitors (efficacy)
ALK Inhibitors
Dr. Cheryl Ho
Monitoring and Surveillance
EARLY STAGE NSCLC
- Resection favoured if surgical candidate
- Baseline staging with CT C/A/P, CT Brain (or MRI), PET scan and EBUS staging
- New data emerging for nivo + 3 cycles platinum doublet chemo neoadjuvant for resectable stage IB-IIIA
- SABR for non surgical candidates
- MO review post op 3-4 weeks for adj chemo/TKI indications
- Send for ALTER (eArLy sTage EgfR testing) for adj osimertinib
STAGE III - NON-RESECTABLE
- Baseline staging with CT C/A/P, CT Brain (or MRI), PET scan
- CRT (cisplatin preferred X 2 cycles), start chemo with Day 1 RT
- Weekly carbo/taxol for cis ineligible
- GPO/MO assess q 2 weekly
- Avoid GCSF with concurrent RT therefore levofloxacin prophylaxis
- Organize imaging 1-2 weeks post RT
- If stable/response then consider adj durvalumab X 1 year
SURVEILLANCE
- Preference for thoracic surgery to conduct surveillance for resected lung ca and rad onc for SABR (Stereoactive Ablative Radiotherapy) pts
- Generally med onc responsible for surveillance for CRT pts
- For resected stage I-III lung ca:
- Thoracic imaging q 6 monthly X 2-3 years (CT preferred)
- H/P q 6 monthly X 2-3 years
- Consider annual non-contrast low dose CT for high risk patients
- >20 pack years, current smokers or quit within 15 years
- May require closer monitoring for indeterminant nodules/GGO (adenocarcinoma in situ potential)
- For stage I/II treated with SABR
- Rad Onc should survey
- H/P and thoracic imaging (CT preferred) q 3-6 months X 3 years, then q 6 monthly years 4,5
- Consider annual non-contrast low dose CT for high risk patients
- >20 pack years, current smokers or quit within 15 years
- For CRT patients
- Generally MO surveillance or alternating MO/RO
- Most will receive adjuvant durvalumab
- Proposed BC Cancer guidelines:
- CT C/A/P and CT brain q6 monthly X 2 years
- Reasonable to substitute CT brain for MRI brain (local radiology preference)
- LD non-contrast CT chest/upper abdo annual to 5 years
- Consider d/c to family doctor after 2 years surveillance
- Consider annual non-contrast low dose CT for high risk patients
- >20 pack years, current smokers or quit within 15 years
- Lifestyle modifications: counselling re smoking cessation
- Consider radon testing, especially non-smokers
Dr. Michael Humphreys
METASTATIC NSCLC
MONITORING
- Tissue is vital, need PD-L1 and FOCUS Panel for adenos
- Need baseline CT brain/C/A/P and bone scan (unless PET done)
- CEA q cycle if elevated at baseline
- For patients with PD-L1 regardless of histology generally will get upfront first line pembro
- First efficacy assessment with CT C/A/P (add bone scan if bone mets) prior to cycle 4
- If progression, repeat in 4 weeks to r/o pseudoprogression
- For responders image q 3 monthly, for durable responders may increase interval to q 6 monthly
- IO: IO panel prior to each cycle and then min of q 3 monthly X year post discontinuation/completion
- For SCC, PD-L1 < 50%: most will get carbo/taxol (paclitaxel)/pembro first line
- First efficacy assessment with CT C/A/P (add bone scan if bone mets) prior to cycle 4
- Stable or response transition to maintenance pembro for cycle 5
- Imaging q 3 cycles on maintenance initially, for durable responders may increase interval up to q 6 monthly
- For Adenos with no driver mutation and PD-L1 <50%: most will get carbo/pem/pembro
- B12 and folic acid starting 1 week pre treatment, ensure compliance, continue for 1 month post discontinuation of pemetrexed
- First efficacy assessment with CT C/A/P (add bone scan if bone mets) prior to cycle 4
- Stable or response transition to maintenance pembro/pemetrexed for cycle 5
- Imaging q 3 cycles on maintenance initially, for durable responders may increase interval up to q 6 monthly
- Ignore mid cycle CBC monitoring on protocol (unnecessary)
- Stable or response transition to maintenance pembro/pemetrexed for cycle 5
- First line TT for driver mutation (EGFR/ALK/ROS/NTRK)
- Baseline CT C/A/P, MRI brain, bone scan (omit if PET scan)
- Image at 2 months (generally respond very quickly)
- Include CT brain (or MRI brain) for monitoring as high predilection to brain mets
- Subsequent imaging q 3 months, for durable responders may increase interval to q 4-6 months. CEA rise / symptoms prompts earlier restaging.
- EGFR – prefer chemo second/third line – poor response to IO
- ALK+ – prefer serial ALK inhibition
- Consider SRE prophylaxis (densumab via palliative care benefits) for ++ bone mets
- Stable or response transition to maintenance pembro for cycle 5
- First efficacy assessment with CT C/A/P (add bone scan if bone mets) prior to cycle 4
Dr. Michael Humphreys
SCLC
LIMITED STAGE
- Baseline staging with CT C/A/P, MRI brain (preferred), PET scan
- Stage I (EBUS neg) – resection and then adj cis/etopX4
- Majority have med LN+ and receive CRT
EXTENSIVE DISEASE
- Baseline staging with CT C/A/P, MRI brain (preferred), Bone scan (omit if PET scan)
- Disease not encompassable in an RT field
- Preferred chemo: Carboplatin/Etoposide/durvalumab
- CT C/A/P and CT brain post cycle 2,4
- 4 cycles Carboplatin/etop total, continue with maintenance durva until progression
- Rad Onc to consider consolidative thoracic RT for patients with limited extrathoracic disease and good response to bulky thoracic disease
- Rad Onc to consider PCI
SURVEILLANCE LIMITED STAGE
- MRI brain (preferred) q 3-4 months during year 1, then q 6 months during year 2 (regardless of PCI status) as per NCCN guidelines
- CT C/A/P 2 months post treatment, then Q 3 months for 2 years, then q 6 months until 5 years post treatment
- H/P q 3 monthly X 2 years, then q 6 monthly year 3, then annual
- Consider annual non-contrast low dose CT for high risk patients
- >20 pack years, current smokers or quit within 15 years
- Consider discharge to family doctor after 3-5 years surveillance
SURVEILLANCE EXSTENSIVE STAGE
- MRI brain (preferred) q 3-4 months during year 1, then q 6 months during year 2 (regardless of PCI status) as per NCCN guidelines
- CT C/A/P 2 months post chemotherapy, then Q 3 months for 2 years, then q 6 months until 5 years post treatment
- F/u monthly while on durvalumab, with IO panel
- Weak evidence for serum chromogranin A monitoring
- For patients completed treatment with no progression
- H/P q 2 months year 1, then q 3 monthly years 2-3, then q 6 monthly years 4-5, then annually
- Generally do not discharge patients, but could consider at year 5
- Imaging as above
