Neoplasms of the Lung¶
Part 4: Oncology and Hematology | Part 4 – Oncology: Solid Tumors · Part 4 – Oncology: Solid Tumors · Chapter 83
Key Clinical Points¶
- Stopping tobacco use before middle age avoids >90% of lung cancer risk attributable to tobacco.
- LDCT screening reduces lung cancer mortality by 20% (95% CI, 6.8–26.7%) compared to CXR.
- Patients with PD-L1 expression ≥20% have marked survival benefit with pembrolizumab as single agent.
- TTF-1 is positive in >70% of pulmonary adenocarcinomas and indicates primary lung cancer.
- Nearly 90% of SCLCs harbor TP53 and RB1 mutations.
- USPSTF 2021 criteria: LDCT screening for individuals aged 50–80 with ≥20 pack-year history who currently smoke or quit within past 15 years.
- African Americans have highest age-adjusted lung cancer rates, with excess mortality among men.
- SIADH resolves in 1–4 weeks during chemotherapy initiation.
- Annual LDCT screening has NNTS of 320 to prevent one lung cancer death (NLST data).
- Pancoast syndrome involves apex tumor extension with C8-T2 nerve involvement and shoulder pain.
1. DEFINITION & OVERVIEW¶
• Definition: Lung cancer is defined by WHO as tumors arising from respiratory epithelium (bronchi, bronchioles, alveoli). • Classification: ◦ Divided into four major types: 1. Small-cell lung cancer (SCLC) 2. Adenocarcinoma 3. Squamous cell carcinoma 4. Large-cell carcinoma • Adenocarcinoma Characteristics: ◦ Show glandular differentiation or mucin production. ◦ Patterns: acinar, papillary, lepidic, or solid. ◦ Most common in never-smokers, women, and younger adults (<60 years). • Squamous Cell Carcinoma Characteristics: ◦ Exhibit keratinization/intercellular bridges from bronchial epithelium. • Large-cell Carcinoma Characteristics: ◦ Lack features of SCLC and lack glandular/squamous differentiation.
1.1 Histologic Subtypes & Immunohistochemistry¶
• Adenocarcinoma Patterns: ◦ Lepidic (favorable prognosis) ◦ Acinar/Papillary (intermediate) ◦ Solid (poor) ◦ Note: Terms like signet ring/clear cell have been eliminated; micropapillary subtype added for poor prognosis. • IHC Markers: ◦ TTF-1: Positive in >70% of pulmonary adenocarcinomas; distinguishes primary lung cancer from metastatic tumors. ◦ Napsin-A: Expressed in >90% of primary lung adenocarcinomas. ◦ Cytokeratins 7/20: Help differentiate NSCLC (CK7+/CK20-) from squamous cell carcinoma (CK7-/CK20-). ◦ p63: Identifies squamous differentiation in cytologic samples. ◦ Mesothelioma markers: CK5/6, calretinin, and WT-1. • Table 83-1 (Genetic Alterations): ◦ ALK: Rearrangement (3–7%) in Adenocarcinoma. ◦ EGFR: Mutation (10–35%) in Adenocarcinoma. ◦ KRAS: Mutation (15–25%) in Adenocarcinoma. ◦ ROS1: Rearrangement (1–2%) in Adenocarcinoma. ◦ BRAF: Mutation (1–3%) in Adenocarcinoma.
2. EPIDEMIOLOGY¶
• Global Impact: Second most common cancer globally (2.2M diagnosed in 2020); leading cause of cancer death (1.8M deaths). • Risk & Incidence: ◦ Peak incidence at age 80. ◦ Lifetime risk: 1/16 for males; 1/17 for females. • Demographics: ◦ African Americans: Highest age-adjusted rates (excess mortality in men). ◦ Hispanic/Native Americans: ~40–50% of Caucasian rates. ◦ African-American women <50 years: Mortality >25% higher than Caucasians. • Trends: Declining incidence (-2.5%/year in men, -1%/year in women) due to reduced smoking and improved screening/therapy.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
• Smoking Impact: ◦ 10-fold risk increase compared to never-smokers. ◦ One mutation per 15 cigarettes smoked. • Environmental/Other Factors: ◦ ETS: Increases risk ~20–30% in never-smokers. ◦ Radon: Exposure may equal or exceed ETS risk. • Genetic & Molecular Drivers: ◦ SCLC: 90% harbor TP53 and RB1 mutations. ◦ Never-smokers: Higher incidence of T790M EGFR mutation. ◦ General: Chromosome 3p loss occurs early; tumor suppressor genes include LKB1, FHIT, and CDKN2A/B. • Histology-Specific Alterations: ◦ Adenocarcinomas: Frequent genomic alterations (EGFR/KRAS/ALK). ◦ Squamous cell carcinomas: FGFR1 amplification, DDR2 mutations, and PIK3CA/PTEN loss.
3.1 Molecular Pathogenesis¶
• Hallmarks of Cancer: ◦ Growth signaling autonomy ◦ Anti-apoptosis ◦ Replicative immortality ◦ Angiogenesis ◦ Invasion/metastasis
4. CLINICAL FEATURES¶
• Presentation: Over 50% present with advanced/metastatic disease. • General Symptoms: ◦ Chronic cough/hemoptysis (smokers). ◦ Unresponsive pneumonia. ◦ Constitutional: weight loss >10%. • Paraneoplastic Syndromes: ◦ Hypercalcemia (PTHrP) ◦ SIADH (hyponatremia) → resolve in 1–4 weeks with fluid restriction/demeclocycline/tolvaptan. ◦ Cushing’s syndrome (ectopic ACTH). ◦ Eaton-Lambert syndrome, polymyositis. • Local Effects: ◦ Clubbing (30% NSCLC). ◦ Tracheal obstruction, SVC syndrome, malignant pleural effusion. • Table 3 (Symptoms & Frequency): ◦ Cough: 8–75% ◦ Dyspnea: 3–60% ◦ Hemoptysis: 6–35% ◦ Clubbing: 0–20% ◦ Weakness: 0–10% ◦ Dysphagia: 0–2%. • Table 4 (Metastatic Indicators): ◦ Constitutional: weight loss >10 lb. ◦ Musculoskeletal: pain. ◦ Neurologic: headaches, syncope, seizures, extremity weakness, mental status change. ◦ Lab findings: Hematocrit <40% (men) or <35% (women); elevated Alk Phos, GGT, SGOT, and Calcium.
4.1 Regional Spread & Paraneoplastic Syndromes¶
• Superior Sulcus Tumors: ◦ Pancoast syndrome: → apex tumor extension → C8-T2 nerve involvement → shoulder pain. ◦ SVC syndrome, pericardial tamponade.
5. DIFFERENTIAL DIAGNOSIS¶
• NSCLC Differentiation: ◦ Adenocarcinoma: TTF-1+, Napsin-A+. ◦ Squamous cell carcinoma: p40+, p63+. • Mesothelioma Differentiation: ◦ Markers: CK5/6, calretinin, and WT-1. • Diagnostic Strategy: Repeat biopsy recommended for NOS tumors.
6. INVESTIGATIONS & DIAGNOSIS¶
• Screening (LDCT): ◦ Reduces mortality by 20% vs. CXR (95% CI, 6.8–26.7%). ◦ USPSTF Criteria: Age 50–80, ≥20 pack-year history, current smoker or quit <15 years. ◦ Harms: 25% false positives, radiation (~1.5 mSv), overdiagnosis of indolent tumors; 10–15% false negatives. ◦ Benefit: NNTS of 320 to prevent one death.
6.1 Screening Criteria & Harms¶
• Solitary Pulmonary Nodule (Figure 83-5): Step 1: Serial high-resolution CT at 3, 6, 9, 12, 18, and 24 months. Step 2: If results are "Negative" → End of pathway. Step 3: If "Inconclusive/Requires further investigation" → Additional testing (PET if ≥ 1 cm; Contrast-enhanced CT; Transthoracic fine-needle aspiration; or Bronchoscopy if "air-bronch sign" present). Step 4: After additional testing: - If "Negative" → End of pathway. - If "Positive" → VATS (evaluation of frozen section, followed by lobectomy if nodule is malignant).
7. MANAGEMENT & TREATMENT¶
- NSCLC Early-Stage: → Surgery (lobectomy) with adjuvant chemotherapy/radiotherapy.
- NSCLC Locally Advanced: → Chemoradiation.
- NSCLC Metastatic (Targeted Therapy - Figure 83-6 & Table 12): → EGFR Exon 19 deletion / L858R → Atinib, Deucotinib, Erlotinib (+ramucirumab, +bevacizumab), Gefitinib, Osimertinum, Osimertinum+chemotherapy. → EGFR Exon 20 Insertion → Amivantamab + Carfilzomib, Premetrect (non-squamous). → ALK fusion → Alectinib, Brigatinib, Ceritinib, Crizotinib, Lorlatinib. → KRAS G12C → Adagrasib (*Note: 2nd line only), Sotorasib. → HER2 mutation → Fam-trastuzumab deruxtecan-nx1, Ado-trastuzumab emtansine. → ROS1 fusion → Crizotinib, Entrectinib, Repotrectinib (Ceritinib, Lorlatinib). → RET fusion → Prasitinib, Selpercatinib. → MET exon 14 skipping → Capmatinib, Crizotinib, Tepotinib. → BRAF V600E → Dabrafenib/Trametinib, Encorafenib/Binimetinib, Vemurafenib. → NTRK 1/2/3 fusion → Entrectinib, Larotrectinib. → Atypical EGFR (G719X, L861Q, S768E) → Afatinib.
- NSCLC Metastatic (Immunotherapy - Figure 83-7 & Table 13): → PD-L1 ≥ 50% → Anti-PD-1/PD-L1 monotherapy OR + chemotherapy. → PD-L1 ≥ 1% (but <50%) → Options: Monotherapy + chemo; Anti-PD-1 + Anti-CTLA-4; or Anti-PD-1 + Anti-CTLA-4 + chemo. → PD-L1 < 1% → Options: Monotherapy + chemo OR Anti-PD-1 + Anti-CTLA-4 + chemo. → PD-L1 < 50% and ALK/ROS1 negative → Options: Monotherapy + chemo OR Anti-PD-1 + Anti-CTLA-4 + chemo.
- SCLC Management (Figure 83-8): Step 1: Initial Workup (Assess for metastasis). Step 2: If "No signs/symptoms of metastasis":
- No contraindication to combined chemoradiation → Combined-modality (platinum + etoposide + radiation).
- Contraindication to combined → Sequential treatment (chemotherapy then radiation). Step 3: If "Single lesion detected" on imaging:
- Biopsy Negative for metastasis → Combined-modality (platinum + etoposide + radiation).
- Biopsy Positive for metastasis → Chemotherapy with immunotherapy and/or surgery for palliation. Step 4: If "Multiple lesions detected" on imaging:
- Biopsy Negative for metastasis → Combined-modality (platinum + etoposide + radiation).
- Biopsy Positive for metastasis → Chemotherapy with immunotherapy and/or surgery for palliation.
Pharmacologic Management¶
• Targeted Agents: ◦ EGFR: Erlotinib, Osimertinum. ◦ ALK: Crizotinib, Alectinib. ◦ ROS1: Entrectinib. ◦ PD-1/PD-L1 Inhibitors: Pembrolizumab (benefit if PD-L1 ≥20%), Nivolumab. • Chemotherapy: ◦ Platinum-based regimens (carboplatin/paclitaxel). ◦ SCLC: etoposide/cisplatin with prophylactic cranial irradiation. ◦ Relapsed SCLC: topotecan or immunotherapy.
8. PROGNOSIS & COMPLICATIONS¶
• Prognosis: ◦ Overall 5-year survival ≈ 16% for all stages. ◦ Stage I: ~49%; Stage IV: <5%. ◦ SCLC: Poor prognosis, median survival 8–12 months. • Treatment Complications: ◦ Chemotherapy: Neutropenia (40%), anemia (25%), thrombocytopenia (30%). ◦ Immunotherapy: Pneumonitis (5–10%), fatigue (30%), rash (15%). ◦ Radiation: Esophagitis (30%), radiation pneumonitis (20%). ◦ Targeted therapy: Rash (60%), diarrhea (40%), and QT prolongation. • Clinical Trial Data: ◦ FLAURA: Osimertinum showed superior ORR (83%) and PFS (16.7 months) vs. chemotherapy. ◦ CROWN: Lorlatinib showed high ORR (76%) in ALK-positive cases.
9. SPECIAL CONSIDERATIONS¶
• Never-Smokers: ◦ Higher incidence of EGFR/ALK mutations. ◦ Distinct molecular profiles compared to smokers. • High Risk Groups: ◦ Germline mutations (14.9% of patients) indicate higher hereditary risk. ◦ Screening eligibility includes never-smokers with family history (1.4% detection rate in Taiwan study).
10. KEY PEARLS & CLINICAL TRAPS¶
• Pearls: ◦ TTF-1/Napsin-A distinguish adenocarcinoma; PD-L1 ≥20% predicts pembrolizumab benefit; Pancoast syndrome involves C8-T2 nerve involvement. ◦ Lung cancer is the leading cause of cancer death globally. • Traps: ◦ Never-smoker lung cancer may present atypically. ◦ SIADH resolves in 1–4 weeks with fluid restriction. ◦ SCLC has poor prognosis despite initial response to chemo/radiation.
Reference Tables¶
TABLE 83-1 Genetic Alterations with Existing Therapies in Non-Small- Cell Lung Cancer¶
Harrison's 22e, p.617
| GENE | ALTERATION | FREQUENCY IN NSCLC |
TYPICAL HISTOLOGY |
|---|---|---|---|
| ALK | Rearrangement | 3–7% | Adenocarcinoma |
| Mutation | 1–3% | ||
| EGFR | Mutation | 10–35% | Adenocarcinoma |
| Mutation | 2–4% | ||
| KRAS | Mutation | 15–25% | Adenocarcinoma |
| Amplification | 2–4% | ||
| NRAS | Mutation | 1% | Adenocarcinoma |
| Rearrangement | 1–2% | ||
| RET | Rearrangement | 1–2% | Adenocarcinoma |
| Rearrangement | 1–2% |
TABLE 83-2 The Benefits and Harms of LDCT Screening for Lung Cancer Based on NLST Data Benefits: How did CT scans help…¶
Harrison's 22e, p.618
| LDCT | CXR | |
|---|---|---|
| Benefits: How did CT scans help compared to CXR? | ||
| 4 in 1000 fewer died from lung cancer | 13 in 1000 | 17 in 1000 |
| 5 in 1000 fewer died from all causes | 70 in 1000 | 75 in 1000 |
| Harms: What problems did CT scans cause compared to CXR? | ||
| 365 in 1000 | ||
| 25 in 1000 | ||
| 3 in 1000 |
TABLE 83-3 Presenting Signs and Symptoms of Lung Cancer¶
Harrison's 22e, p.618
| SYMPTOM AND SIGNS | RANGE OF FREQUENCY |
|---|---|
| Cough | 8–75% |
| Dyspnea | 3–60% |
| Hemoptysis | 6–35% |
| Clubbing | 0–20% |
| Weakness | 0–10% |
| Dysphagia | 0–2% |
TABLE 83-4 Clinical Findings Suggestive of Metastatic Disease Symptoms elicited in history¶
Harrison's 22e, p.619
| Symptoms elicited in history |
• Constitutional: weight loss >10 lb • Musculoskeletal: pain • Neurologic: headaches, syncope, seizures, extremity weakness, recent change in mental status |
|---|---|
| Routine laboratory tests |
• Hematocrit, <40% in men; <35% in women • Elevated alkaline phosphatase, GGT, SGOT, and calcium levels |
TABLE 83-5 TNM Staging System for Lung Cancer (Eighth Edition) Primary Tumor (T) T1¶
Harrison's 22e, p.622
| Primary Tumor (T) | |
|---|---|
| T1 | Tumor ≤3 cm diameter, surrounded by lung or visceral pleura, without invasion more proximal than lobar bronchus |
| T1mi | Minimally invasive adenocarcinoma (pure lepidic pattern, <3 cm in greatest dimension and <5 mm invasion)—T1a (size ≤1 cm)— T1b (1 cm < size ≤ 2 cm)—T1c (2 cm < size ≤ 3 cm) |
| T2 | Tumor >3 cm but ≤5 cm, or tumor with any of the following features: |
| Involves main bronchus without carina, regardless of distance from carina |
|
| Invades visceral pleura | |
| Associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung |
|
| T2a | Tumor >3 cm but ≤4 cm |
| T2b | Tumor >4 cm but ≤5 cm |
| T3 | Tumor >5 cm but ≤7 cm or any of the following: |
| Directly invades any of the following: chest wall, pericardium, phrenic nerve |
|
| Separate (satellite) tumor nodules in the same lobe | |
| T4 | Tumor >7 cm or any tumor with invasion of mediastinum, diaphragm, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, or carina, or with separate (satellite) tumor nodules in a different ipsilateral lobe |
| Nodal Stage (N) | |
| Metastases (M) | |
| M0 | No distant metastasis |
| M1 | Distant metastasis |
| M1a | Separate tumor nodule(s) in a contralateral lobe; pleural/ pericardial nodule/malignant effusion |
| M1b | Single extrathoracic metastasis, including single nonregional lymph node |
| M1c | Multiple extrathoracic metastases in one or more organs |
TABLE 83-6 TNM Stage Groupings, Eighth Edition T/M T1¶
Harrison's 22e, p.622
| T/M | Subcategory | N0 | N1 | N2 | N3 |
|---|---|---|---|---|---|
| T1a T1b T1c |
IA1 IA2 IA3 |
IIB IIB IIB |
IIIA IIIA IIIA |
||
| T2 | T2a | IB | IIB | IIIA | IIIB |
| T2b | IIA | IIB | IIIA | IIIB | |
| T3 | IIB | IIIA | IIIB | ||
| T4 | T4 | IIIA | IIIA | IIIB | IIIC |
| M1a M1b M1c |
IVA IVA IVB |
IVA IVA IVB |
IVA IVA IVB |
TABLE 83-7 Assessment of Risk of Cancer in Patients with Solitary Pulmonary Nodules VARIABLE Diameter (cm) Age (years)…¶
Harrison's 22e, p.623
| VARIABLE LOW | RISK | |
|---|---|---|
| INTERMEDIATE | HIGH | |
| Diameter (cm) <1.5 | 1.5–2.2 | ≥2.3 |
| 45–60 | ||
| Smoking status Never s | moker Current smoker (<20 cigarettes/ |
Current smoker d) (>20 cigarettes/d) |
| years Quit <7 years ag quit |
||
| Characteristics of Smooth nodule margins |
Scalloped | Corona radiata or spiculated |
TABLE 83-8 Select References to Professional Guidelines, in Alphabetical Order 1 2. 3. 4.¶
Harrison's 22e, p.624
| 1 | American Society of Clinical Oncology (ASCO), Thoracic Cancer |
|---|---|
| 3. | International Association for the Study of Lung Cancer (IASLC), Guidelines |
TABLE 83-9 Adjuvant Chemotherapy Trials in Non-Small-Cell Lung Cancer¶
Harrison's 22e, p.625
| TRIAL | STAGE | TREATMENT | NO. OF PATIENTS |
5-YEAR SURVIVAL (%) |
P |
|---|---|---|---|---|---|
| IALT | I–III | Cisplatin-based Control |
932 835 |
44.5 40.4 |
< .03 |
| IB–II | Cisplatin + vinorelbine Control |
242 240 |
69 54 |
||
| ANITA | IB–IIIA | Cisplatin + vinorelbine Control |
407 433 |
60 58 |
.017 |
| I–III | MVP Control |
548 540 |
50 45 |
||
| BLT | I–III | Cisplatin-based Control |
192 189 |
60 58 |
.90 |
| IB | Carboplatin + paclitaxel |
173 171 |
59 57 |
||
| ECOG1505 | IB > 4c – IIIA |
Cisplatin-based Cisplatin-based + bevacizumab |
749 752 |
NR NR |
.90 |
TABLE 83-10 Select Therapeutic Strategies Incorporating Immunotherapy or Targeted Therapy In Early-Stage, Resectable…¶
Harrison's 22e, p.625
| TRIAL | STAGE AND DISEASE CHARACTERISTICS |
REGIMEN | APPROVAL ENDPOINT |
|---|---|---|---|
| Neoadjuvant | |||
| CheckMate 816 |
IB–IIIA Irrespective of PD-L1 |
Nivolumab + chemotherapy × 3 cycles |
EFS HR 0.63, p = .005 |
| Perioperative | |||
| II–IIIB (N2) Irrespective of PD-L1 |
Pembrolizumab + chemotherapy × 4 cycles → surgery → pembrolizumab × ~9 months |
||
| Adjuvant | |||
| IMPower010 | II–IIIA PD-L1 positive (≥1%) |
Adjuvant chemotherapy → atezolizumab × 1 year |
DFS HR 0.66, p = .004 |
| IB–IIIA Irrespective of PD-L1 |
Adjuvant chemotherapy → pembrolizumab × 1 year |
||
| ADAURA | IB–IIIA EGFR exon 19 deletions or exon 21 L858R |
Osimertinib × 3 years (irrespective of adjuvant chemotherapy) |
DFS HR 0.20, p < .0001 OS HR 0.49, p < .001 |
| IB-IIIA ALK fusion positive |
Alectinib × 2 years |
TABLE 83-11 Phase 3 Trials of EGFR TKIs in EGFR-Positive Non-Small-Cell Lung Cancer¶
Harrison's 22e, p.627
| TRIAL | THERAPY | NO. OF PATIENTS |
ORR (%) | PFS (MONTHS) |
|---|---|---|---|---|
| IPASS | CbP | 129 | 47 | 6.3 |
| Gefitinib | 132 | 71 | 9.3 | |
| CG Erlotinib |
87 86 |
15 58 |
||
| OPTIMAL | CG | 72 | 36 | 4.6 |
| Erlotinib | 82 | 83 | 13.1 | |
| CG Gefitinib |
114 114 |
31 74 |
||
| WJTOG3405 | CD | 89 | 31 | 6.3 |
| Gefitinib | 88 | 62 | 9.2 | |
| CP Afatinib |
115 230 |
23 56 |
||
| LUX LUNG 6 | CG | 122 | 23 | 5.6 |
| Afatinib | 242 | 67 | 11.0 | |
| Erlotinib Afatinib |
159 160 |
58 73 |
||
| ARCHER 1050 | Gefitinib | 225 | 72 | 9.2 |
| Dacomitinib | 227 | 75 | 14.7 | |
| Erlotinib or gefitinib Osimertinib |
277 279 |
76 80 |
||
| FLAURA2 | Osimertinib/ chemotherapy |
279 | 83 | 25.5 |
| Osimertinib | 278 | 76 | 16.7 | |
| Amivantamab/ lazertinib Osimertinib |
429 429 |
86 85 |
TABLE 83-12 Results of Phase 3 Trials Comparing First-Line ALK Inhibitors in ALK-Positive¶
Harrison's 22e, p.628
| TRIAL | THERAPY | NO. OF PATIENTS |
ORR (%) | MEDIAN PFS | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Profile 1014 | Crizotinib | 172 | 74 | 10.9 | ||||||
| Platinum- chemotherapy |
171 | 45 | 7.0 | |||||||
| Alectinib Crizotinib |
152 151 |
82.9 75.5 |
||||||||
| ALTA1L | Brigatinib | 137 | 71 | 67% at 24 months | ||||||
| Crizotinib | 138 | 60 | 43% at 11 months | |||||||
| Ensartinib Crizotinib |
121 126 |
75 67 |
||||||||
| CROWN | Lorlatinib Crizotinib |
149 147 |
76 58 |
64% at 60 months 9.1 |
||||||
| EGFR Exon 19 deletion and EGFR L858R |
EGFR Exon 20 Insertion |
ALK fusion | KRAS G12C | ERBB2 (HER2) mutation |
ROS1 fusion | RET fusion | MET exon 14 skipping mutation |
BRAF V600E mutation |
NTRK 1/2/3 Fusion |
Atypical EGFR mutations: G719X, L861Q, and S768I |
| Afatinib, Dacomitinib, Erlotinib, Erlotinib + ramucirumab, Erlotinib + bevacizumab, Gefitinib, Osimertinib, Osimertinib + chemotherapy |
Amivantamab + Carboplatin/ Pemetrexed (nonsquamous) |
Alectinib Brigatinib Ceritinib Crizotinib Lorlatinib |
Adagrasib, Sotorasib |
Fam- trastuzumab deruxtecan-nxki, Ado-trastuzumab emtansine |
Crizotinib, Entrectinib, Repotrectinib, (Ceritinib), (Lorlatinib) |
Pralsetinib, Selpercatinib |
Capmatinib, Crizotinib, Tepotinib |
Dabrafenib/ Trametinib, Encorafenib/ Binimetinib, Vemurafenib |
Entrectinib Larotrectinib |
Afatinib |
TABLE 83-13 Results of Phase 3 Trials Comparing First-Line Immunotherapy with or without Chemotherapy Versus…¶
Harrison's 22e, p.630
| STUDY | THERAPY | NO. OF PATIENTS | OS (MONTHS) | PFS (MONTHS) |
|---|---|---|---|---|
| KEYNOTE-024 | Pembrolizumab | 154 | 30.0 | 7.9 |
| Platinum-chemotherapy | 151 | 14.2 | ||
| KEYNOTE-042 | Pembrolizumab | 637 | 16.7 | 5.4 |
| Platinum-chemotherapy | 637 | 12.1 | ||
| IMPOWER 110 | Atezolizumab | 286 | 20.2 | 8.1 |
| Platinum-chemotherapy | 263 | 13.1 | ||
| KEYNOTE-189 | Pembrolizumab + platinum-chemotherapy | 410 | NR | 8.8 |
| Platinum-chemotherapy | 206 | 11.3 | ||
| KEYNOTE-407 | Pembrolizumab + platinum-chemotherapy | 278 | 15.9 | 6.4 |
| Platinum-chemotherapy | 281 | 11.3 | ||
| IMPOWER 150 | Atezolizumab + platinum-chemotherapy | 356 | 19.2 | 8.3 |
| Platinum-chemotherapy | 336 | 14.7 | ||
| IMPOWER 130 | Atezolizumab + platinum-chemotherapy | 483 | 18.6 | 7.0 |
| Platinum-chemotherapy | 240 | 13.9 | ||
| EMPOWER-Lung 3 | Cemiplimab + platinum-chemotherapy Platinum-chemotherapy |
312 154 |
21.9 13.0 |
8.2 5.0 |
| Nivolumab + ipilimumab Platinum-chemotherapy |
583 583 |
17.1 13.9 |
||
| CheckMate-9LA | Nivolumab + ipilimumab plus two cycles of platinum-chemotherapy |
361 | 14.1 | 6.8 |
| Platinum-chemotherapy | 358 | 10.7 | 5 | |
| Tremelimumab + durvalumab and platinum-chemotherapy Platinum-chemotherapy |
338 337 |
14 11.7 |