lung CA tx Flashcards
PACIFIC trial
durva x1y ⇒ ↑PFS,OS
(after definitive chemoRT)
in locally adv, unresectable III
PD-L1: ???
IMpower 010
atezo x1y ⇒ ↑DFS (overall), OS (only in PD-L1≥50%)
(after adjuvant platinum-based doublet chemo)
in IB(7e:≥4cm)-IIIA
PD-L1: ≥1% (+)
CheckMate 816
neoadjuvant chemoIO:
platinum-based doublet + nivo
⇒ ↑EFS & cPR=24%
KEYNOTE-671
periop chemoIO:
neoadjuvant chemoIO:
platinum-based doublet + pembro
+
adjuvant IO:
pembro x10mo
⇒ ↑EFS & cPR=18%
Lung ART
mediastinal PORT (postop RT) for resected NSCLC with pN2:
non-sig 3% higher 3y DFS;
10% ↓ recurrence offset by 10% ↑ death (mostly cardiopulm)
RT (3D conformal > IMRT) to:
- resected +LNs
- downstaged +LNs (if neoadj)
- bronchial stump
- ipsilateral hilar LN region
- “probable extension to mediastinal pleura adjacent to completely resected tumor bed”
- levels 4,7 routinely
with margin of 1cm for nodes
NCCN guideline adjuvant systemic tx indication(s) & regimens for resected NSCLC
all for xx-IIIA+T3N2-IIIB
**PD-L1⊕(≥1%)** high-risk IIA/IIB+
chemo → atezo x1y
**PD-L1⊖(<1%)** high-risk IIA/IIB+
chemo ± atezo x1y
**PD-L1 any** II+ completing KEYNOTE-671 periop tx
atezo x1y
**EGFR** IB+
chemo → osi x3y
**ALK** II+
alectinib x2y
ADAURA
osi x3y ⇒ ↑DFS(II-IIIA),DFS(all),OS
(after adjuvant platinum-based doublet chemo)
in resected IB(4cm)-IIIA NSCLC (adjuvant)
EGFR⊕
KEYNOTE-024
pembro x2y ⇒ ↑PFS,OS,RR
in IV NSCLC
PD-L1≥50%
NCCN guideline 1st-line tx for NSCLC cIV EGFR/ALK⊖ & PD-L1≥50%
pembro x2y
(KEYNOTE-024)
mgmt of Pancoast/superior sulcus NSCLC with N2 dz
NO BENEFIT from resxn:
definitive chemoRT + durva (PACIFIC)
NCCN guideline mgmt options for locally advanced N2 (IIIA:T1-2N2 & IIIB:T3N2 = T1-3N2) NSCLC
non-Pancoast
- neoadjuvant → resxn
- definitive chemoRT + durva (PACIFIC)
TSRA: IIIA:T1-2N2 neoadjuvant → re-stage → if cleared N2 dz, resxn (if not, NO BENEFIT from resxn per 2000 Bueno study) – also says NOT to resect any IIIB (T3-4N2) and that T3N2 specifically for chest wall invasion do NOT have any benefit from surgery
NCCN guideline recommendation re: re-staging mediastinum after neoadjuvant tx for locally advanced N2 (IIIA:T1-2N2 & IIIB:T3N2 = T1-3N2) NSCLC
non-Pancoast
NOT mandatory
- “Repeat mediastinoscopy, while possible, is technically difficult and has a lower accuracy compared to primary mediastinoscopy. One possible strategy is to perform EBUS (± EUS) in the initial pretreatment evaluation and reserve mediastinoscopy for nodal restaging after neoadjuvant therapy.”
- “Restaging after induction therapy is difficult to interpret, but CT ± FDG-PET/CT should be performed to exclude disease progression or interval development of metastatic disease.”
- “Patients with negative mediastinum after neoadjuvant therapy have a better prognosis.”
TSRA: IIIA:T1-2N2 neoadjuvant → re-stage → if cleared N2 dz, resxn (if not, NO BENEFIT from resxn per 2000 Bueno study) – also says NOT to resect any IIIB (T3-4N2) and that T3N2 specifically for chest wall invasion do NOT have any benefit from surgery
NCCN guideline recommendations re: mgmt of N2 dz NSCLC
non-Pancoast
“A questionnaire was submitted to the NCCN Member Institutions in 2021 regarding their approach to patients with N2 disease. Their responses indicate the patterns of practice when approaching this difficult clinical problem.
- All NCCN Member Institutions treat select N2 patients with multimodality therapy that includes surgery.
- The majority of NCCN Member Institutions prefer EBUS for initial mediastinal staging, reserving mediastinoscopy for possible restaging.
- The majority of NCCN Member Institutions do not pathologically restage mediastinal lymph nodes after induction therapy and prior to surgery.
- All NCCN Member Institutions consider surgery for single-station non-bulky N2 disease.
- Approximately half of the institutions consider surgery for single-station bulky disease, 39% for multi-station non-bulky disease, and 21% for multi-station bulky disease.
- Two-thirds of NCCN Member Institutions prefer induction chemotherapy; one-third prefer chemoradiation.
- The majority require at least stable disease after induction, but do not require radiologic or pathologic response prior to surgery.
- Roughly a half would consider pneumonectomy after induction chemotherapy, but less than a quarter would consider pneumonectomy after chemoradiation.
- Approximately three-fourths would give adjuvant RT for positive residual N2 disease, but only approximately one-fourth would give RT for N2 pathologic complete response.
NCCN guideline mgmt options for locally advanced N2 (IIIB:T4N2) NSCLC
non-Pancoast
- definitive chemoRT + durva (PACIFIC)
TSRA: IIIA:T1-2N2 neoadjuvant → re-stage → if cleared N2 dz, resxn (if not, NO BENEFIT from resxn per 2000 Bueno study) – also says NOT to resect any IIIB (T3-4N2) and that T3N2 specifically for chest wall invasion do NOT have any benefit from surgery
Pancoast/superior sulcus tumor (NSCLC) Intergroup (IG) 0160/SWOG 9416 trial
III: T3-4 N0-1 superior sulcus NSCLC
induction chemoRT (with platinum-based doublet):
cisplatin + etoposide x2cycles + 45Gy over 5w → resxn → cis/etopo x2cycles
NCCN guideline mgmt of Pancoast/superior sulcus T3-4 N0-1 NSCLC
induction chemoRT (with platinum-based doublet):
cisplatin + etoposide x2cycles + 45Gy over 5w → resxn → cis/etopo x2cycles ± adjuvant systemic tx
(per IG 0160/SWOG 9416 trial on III: T3-4 N0-1 superior sulcus NSCLC)
Pancoast/superior sulcus tumor (NSCLC) trial
IG 0160/SWOG 9416 trial
(III: T3-4 N0-1 superior sulcus NSCLC = induction chemoRT x2 cycles → resxn → chemo x2cycles)
NCCN guideline 1st-line chemo regimen for adenoCA NSCLC
platinum-based doublet:
cis/pem (cisplatin + pemetrexed)
NCCN guideline 1st-line chemo regimen for SCC NSCLC
platinum-based doublet:
cis/gem (cisplatin + gemcitabine)
cisplatin + docetaxel
adjuvant chemo benefit for NSCLC
5% OS
NCCN guideline 1st-line adjuvant systemic tx for resected NSCLC
platinum-based doublet chemo (cis/pem adeno & cis/gem squam) ± IO/TT
except ALK⊕ (direct to alectinib)
NCCN guideline adjuvant chemo indication(s) for resected NSCLC
- > 4cm (T2bN0) + high-risk features
- > 5cm (T3+N0)
- N+ (any)
high-risk = poorly-diff, +LVI, +VPI, pNx, [inadequate] wedge resxn
NCCN guideline pathologic high-risk features for consideration of adjuvant chemo for resected NSCLC
- poorly-diff
- +LVI
- +VPI
- pNx
- [inadequate] wedge resxn
NCCN guideline adjuvant IO/TT indication(s) & regimens for resected NSCLC
all for xx-IIIA+T3N2-IIIB
- ALK II+: alectinib (only 1 without chemo)
- EGFR IB+: chemo → osimertinib
- PD-L1⊕(≥1%) high-risk IIA/IIB+: chemo → atezo x1y
- PD-L1⊖(<1%) high-risk IIA/IIB+: chemo ± atezo x1y
- PD-L1 any II+ completing KEYNOTE-671 periop tx: atezo x1y
common biomarker in smoker NSCLC
KRAS
Is NSCLC in a smoker more or less likely to respond to IO than in a non-smoker, with the same molecular profile?
MORE
ever smokers tend to respond better to IO than never smokers
r/t higher PD-L1?
Which biomarkers safely tolerate and/or respond well to IO?
KRAS (smokers)
poss BRAF
approved + effective in PD-L1 neg?
none???
- neoadj nivo (with chemo): ⊕approved / ⊖effective
- adjuvant pembro (after chemo): ⊕approved / ⊖effective
minimum predicted postoperative FEV1 to tolerate resxn
40%
minimum predicted postoperative DLCO to tolerate resxn
40%
minimum preop FEV1 to tolerate pneumonectomy
2L
minimum preop FEV1 to tolerate lobectomy
1L