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Disease Analysis: Non-Small Cell Lung Cancer (NSCLC)

  • ID: 4238712
  • Report
  • April 2021
  • Region: Global
  • 191 Pages
  • Pharma Intelligence
Disease Overview

Lung cancer is generally categorized as either small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC). Of these, NSCLC is the most common type of lung cancer, accounting for roughly 85% of all cases. NSCLC can be further divided into non-squamous and squamous NSCLC histologies. Squamous NSCLC refers to patients with squamous cell carcinoma, whereas non-squamous NSCLC includes patients with adenocarcinoma, large cell carcinoma, and other less common subtypes. Incidence of adenocarcinoma and squamous cell carcinoma varies greatly by both geographic region and gender. In general, adenocarcinoma comprises approximately 30-50% of all lung cancer cases, while squamous cell carcinoma accounts for roughly 25-35%.

Latest Key Takeaways
  • The publisher estimates that in 2018, there were 1.8 million incident cases of non-small cell lung cancer (NSCLC) worldwide, and expects that number to increase to 1.9 million incident cases by 2027. The majority of NSCLC diagnoses (65.4%) worldwide are in males, ranging from 52.9% to 72.1% across regions.
  • In the last three years, the number of therapies targeting specific sensitizing mutations in metastatic NSCLC has drastically increased, permanently altering the treatment landscape. Many of the new drugs have shown dramatically increased response rates over the previous standard-of-care therapies. However, given the relatively small percentage of metastatic NSCLC patients presenting with each oncogenic driver, competition is fierce and first-to-market advantage is critical.
  • Programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1)-targeted monoclonal antibodies for NSCLC are forecast to remain the best-selling class of drugs for this indication. Keytruda was the first PD-1/PD-L1 inhibitor to gain regulatory approval for first-line NSCLC patients without an oncogenic driver and has risen to dominance in this market as label expansions have broadened its target patient population and as late-phase trials have revealed consistently positive data. Furthermore, the commercial potential of this class of drugs will increase over the forecast period as the use of checkpoint inhibitors will likely soon extend beyond the metastatic patient population. Label expansions into the earlier treatment settings may provide an opportunity for the other checkpoint inhibitors to differentiate themselves from Keytruda and carve out a niche in this lucrative market.
  • PD-L1 inhibitor Imfinzi’s approval for sequential therapy of locally advanced patients following chemoradiation minimizes direct competition with established immunotherapies and has allowed the drug to secure a modest market share.
  • Third-generation EGFR inhibitor Tagrisso is now the first-line standard-of-care treatment for NSCLC patients whose tumors harbor activating EGFR mutations (exon 19 deletion or L858R point mutation). Despite competition from Tarceva, Iressa, Gilotrif, Vizimpro, and Alunbrig, Tagrisso will continue to dominate the EGFR inhibitor market due to continued uptake and a recent label expansion into the adjuvant setting. However, Janssen’s recently initiated Phase III MARIPOSA study of amivantamab in combination with lazertinib is the first head-to-head trial against Tagrisso, and the combination could eventually threaten Tagrisso’s position in the first-line setting.
  • Amivantamab and mobocertinib are currently in late-stage development for metastatic NSCLC patients whose tumors harbor an exon 20 insertion mutation in EGFR, a population of patients where currently approved therapies are not effective. Competition will be fierce between these two drugs, and the first therapy to market will likely dominate. However, the relative rarity of this mutation limits the commercial potential of an approval in this patient population, and both therapies are also in development for the treatment of other actionable mutations.
  • Alecensa has become the new first-line standard of care for ALK rearrangement-positive NSCLC. The Phase III ALEX study demonstrated superior progression-free survival when treated with Alecensa compared with previous standard of care Xalkori. Alecensa will likely remain the class leader even though it will face competition in the first-line setting from other ALK inhibitors such as Zykadia, Alunbrig, and Lorbrena. Dual ALK/ROS1 inhibitor Lorbrena is also approved in both the first- and second-line settings, but has experienced only modest uptake thus far.
  • The ALK inhibitors Rozlytrek and Xalkori are both approved for the treatment of metastatic NSCLC patients whose tumors have a ROS1 rearrangement or fusion. Rozlytrek is also approved as a monotherapy for patients with NTRK+ gene fusions. The combined data from Rozlytrek’s development program compare favorably to the data for Xalkori, particularly in patients with CNS metastases at baseline. ROS1 gene rearrangements are present in 1-2% of NSCLC patients, while NTRK fusions are present in approximately 0.2% of cases.
  • The combination of BRAF inhibitor Tafinlar and MEK inhibitor Mekinist has become the standard of care for advanced or metastatic NSCLC with BRAF V600E mutations. However, only 1-2% of NSCLC patients have a BRAF V600E mutation, which limits the combination’s commercial potential.
  • Two MET inhibitors, Tabrecta and Tepmetko, have been approved for NSCLC patients with a MET exon 14 skipping mutation in the US and Japan. Both drugs are also in development for MET-amplified NSCLC and for patients with EGFR-mutated, c-MET-amplified NSCLC who have progressed after EGFR inhibitor treatment. Potential label expansions into these treatment settings represent a noteworthy market opportunity. Approximately 1-4% of NSCLC patients have a MET exon 14 skipping mutation.
  • Retevmo is the first drug approved for the treatment of patients with RET fusion-positive NSCLC. In the pivotal Phase I/II trial, Retevmo demonstrated efficacy in RET fusion-positive patients and in a subgroup of patients with brain metastases. The confirmatory Phase III LIBRETTO-431 trial is ongoing, and approvals in both Europe and Japan are expected based on the Phase I/II data. However, Retevmo will face competition from RET inhibitor Gavreto, which was recently approved in the US.
  • As therapies targeting specific oncogenic drivers have established themselves in metastatic NSCLC, attention has shifted toward mutations that do not yet have targeted therapies. Two notable pipeline examples are KRAS inhibitors sotorasib and adagrasib. Both KRAS inhibitors are being investigated as second-line or later treatments for patients with KRAS G12C-mutant NSCLC, a patient population that was previously thought to be undruggable. This is a significant market opportunity given that approximately 13% of NSCLC patients have KRAS p.G12C mutations.
  • As checkpoint inhibitor regimens dominate in the first-line setting for patients without sensitizing mutations, effective treatments for the post-immunotherapy setting remain the largest unmet need within the indication. Treatment for these patients is largely palliative, and patients currently have very limited treatment options. A number of therapies, including Cabometyx, Lenvima, sitravatinib, and tusamitamab ravtansine, are in development for this treatment setting.
  • The overall likelihood of approval of a Phase I NSCLC asset is 8.1%, and the average probability a drug advances from Phase III is 37.2%. NSCLC drugs, on average, take 9.1 years from Phase I to approval, compared to 9.6 years in the overall oncology space.
  • Key upcoming catalysts for 2021 include top-line results for the Phase III SAPPHIRE study of sitravatinib and Opdivo and the Phase III JAVELIN Lung 100 study of Bavencio, as well as PDUFA dates for amivantamab and adagrasib.
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OVERVIEW
  • Latest key takeaways
DISEASE BACKGROUND
  • Definition
  • Risk factors
  • Symptoms
  • Screening
  • Diagnosis
  • Prognosis
  • Patient segmentation
TREATMENT
  • Early-stage NSCLC (Stage I–II; all subtypes)
  • Advanced NSCLC (Stage IIIa–IIIc; all subtypes)
  • Metastatic NSCLC – molecular profiling
  • Metastatic NSCLC: EGFR+
  • Metastatic NSCLC: EGFR+, second line
  • Metastatic NSCLC: ALK+
  • Metastatic NSCLC: ROS1+
  • Metastatic NSCLC: BRAF V600E mutation
  • Metastatic NSCLC: MET exon 14 skipping
  • Metastatic NSCLC: RET+
  • Metastatic NSCLC: NTRK+
  • Metastatic NSCLC: PD-L1+ (≥50%)
  • Metastatic NSCLC: PD-L1+ (≥1–49%)
  • Metastatic NSCLC: all other
  • Metastatic NSCLC: maintenance therapy
  • Metastatic NSCLC: all other second line or later
EPIDEMIOLOGY
  • Incidence methodology
  • Prevalence of common non-small cell lung cancer biomarkers
MARKETED DRUGS

PIPELINE DRUGS

KEY REGULATORY EVENTS
  • Latecomer Libtayo Wins Coveted First-Line NSCLC Monotherapy Indication
  • Five New EU Filings Leave Starting Blocks At EMA
  • EMD Serono’s Tepmetko Is 6th Novel RTOR Approval
  • Takeda’s Alunbrig For NSCLC
  • World-First Nod For Yuhan's Lung Cancer Drug, In Korea
  • AstraZeneca On Tagrisso's Milestone Advance Into Adjuvant Lung Cancer
  • Tepotinib Among Latest EU Filings
  • Lilly’s Multi-Tumor Treatment Retsevmo Closer To EU Approval
  • Keeping Track: J&J Amivantamab Submitted
  • Oncology, Rare Disease Drugs Dominate New China Approvals
  • Imfinzi Gains Four-Week, Fixed-Dose Regimen
  • Real-Time Oncology Review Welcomes Lorbrena
  • Routine UK Funding OKd For Tagrisso In First & Second-Line NSCLC
  • FDA OKs Blueprint/Roche's Gavreto As Rival To Lilly's Retevmo
  • FDA Approves Guardant’s Guardant360 CDX Comprehensive Genomic Profile
  • AZ’s ‘Practice Changing’ ADAURA Trial Earns Tagrisso’s Third BTD
  • Japan Nods Include Global Firsts For Duvroq, Vafseo And First Local Biosimilar Humira
  • English Funding Success For Roche’s Rozlytrek In NSCLC
  • Roche's Tecentriq Notches Approval For First-Line NSCLC Monotherapy
  • Bristol Wins First Of Two Important Opdivo/Yervoy First-Line NSCLC Approvals
  • US FDA Dismisses Post-Progression Endpoint In Cyramza Lung Cancer Study
PROBABILITY OF SUCCESS

LICENSING AND ASSET ACQUISITION DEALS
  • TRIGR, Elpiscience Partner On Cancer Immunotherapy In China
  • Bayer Enters CAR-T Space With Atara Pact
  • Merck Pays $2.75bn To Access VelosBio’s ROR1-Targeting ADCs
  • AnHeart Acquires Two More Oncology Assets From Daiichi
  • AZ Bets Big On ADCs As It Inks Second, $6bn Deal With Daiichi
  • Roche Backs Blueprint's Precision Therapy Pralsetinib To Challenge Lilly
  • Guardant Will Collaborate With Janssen On Lung Cancer Companion Diagnostic
CLINICAL TRIAL LANDSCAPE
  • Sponsors by status
  • Sponsors by phase
  • Recent events
  • DRUG ASSESSMENT MODEL
  • EGFR inhibitors
  • ROS1 and NTRK gene fusions
  • ALK inhibitors
  • KRAS inhibitors
  • RET inhibitors
  • BRAF inhibitors
  • PARP inhibitors
  • MET inhibitors
  • PD-1/PD-L1 inhibitors
  • TIGIT inhibitor
  • Interleukin 1b antagonist
  • Microtubule inhibitors
  • Folate analog metabolic inhibitor
  • VEGF inhibitors
  • Post-immunotherapy
MARKET DYNAMICS

FUTURE TRENDS
  • Keytruda is forecast to remain the leading immunotherapy approved for NSCLC
  • Checkpoint inhibitors are expected to move into earlier stages of NSCLC
  • Approvals and subsequent uptake for new therapies in the post-immunotherapy setting will contribute significantly to growth in the NSCLC market
  • Alecensa is expected to continue leading the ALK inhibitor class due to strong results in the first-line setting, despite potential competition
  • Tagrisso will remain the best-selling EGFR inhibitor due to continued uptake in the first-line setting and a label expansion into the adjuvant setting
  • New EGFR inhibitors will address the EGFR exon 20 insertion mutation, which is associated with poor response to current treatments
  • The approval and uptake of MET inhibitors is expected to address unmet needs in patients with exon 14 skipping mutations
  • Recent approvals and subsequent uptake of therapies targeting new mutational drivers will support growth in the NSCLC market over the forecast period
  • Generic or biosimilar erosion of key brands will have minimal impact on growth
CONSENSUS FORECASTS

RECENT EVENTS AND ANALYST OPINION
  • Tecentriq for NSCLC (March 21, 2021)
  • Ilaris for NSCLC (March 9, 2021)
  • Keytruda for NSCLC (January 29, 2021)
  • Repotrectinib for NSCLC (January 29, 2021)
  • AMG 510 for NSCLC (January 28, 2021)
  • Amivantamab for NSCLC (January 28, 2021)
  • TAK-788 for NSCLC (January 28, 2021)
  • Bintrafusp Alfa for NSCLC (January 19, 2021)
  • Poziotinib for NSCLC (December 22, 2020)
  • Keytruda for NSCLC (November 9, 2020)
  • Nerlynx for NSCLC (November 5, 2020)
  • Vopratelimab for NSCLC (November 2, 2020)
  • MRTX849 for NSCLC (October 25, 2020)
  • MK-1308 for NSCLC (October 16, 2020)
  • Opdivo for NSCLC (October 7, 2020)
  • AMG 510 for NSCLC (October 5, 2020)
  • Keytruda for NSCLC (September 21, 2020)
  • Libtayo for NSCLC (September 21, 2020)
  • AMG 510 for NSCLC (September 20, 2020)
  • Amivantamab for NSCLC (September 20, 2020)
  • Lorbrena for NSCLC (September 19, 2020)
  • Tagrisso for NSCLC (September 19, 2020)
  • U3-1402 for NSCLC (September 18, 2020)
  • CLN-081 for NSCLC (September 17, 2020)
  • Lenvima for NSCLC (September 17, 2020)
  • Repotrectinib for NSCLC (August 19, 2020)
  • Ensartinib for NSCLC (August 8, 2020)
  • Lorbrena for NSCLC (August 5, 2020)
  • Opdivo for NSCLC (August 3, 2020)
  • Poziotinib for NSCLC (July 27, 2020)
  • SAR408701 for NSCLC (May 31, 2020)
  • Tagrisso for NSCLC (May 31, 2020)
  • Enhertu for NSCLC (May 29, 2020)
  • Opdivo for NSCLC (May 29, 2020)
  • Sym015 for NSCLC (May 29, 2020)
  • Tagrisso for NSCLC (May 29, 2020)
  • Tepmetko for NSCLC (May 29, 2020)
  • Tabrecta for NSCLC (May 14, 2020)
  • Enhertu for NSCLC (May 13, 2020)
  • Opdivo for NSCLC (May 13, 2020)
  • Tagrisso for NSCLC (May 13, 2020)
  • Tiragolumab for NSCLC (May 13, 2020)
  • Libtayo for NSCLC (April 27, 2020)
  • Tagrisso for NSCLC (April 10, 2020)
  • Tedopi for NSCLC (April 1, 2020)
KEY UPCOMING EVENTS

KEY OPINION LEADER INSIGHTS

UNMET NEEDS

BIBLIOGRAPHY
  • Prescription information
APPENDIX

LIST OF FIGURES
Figure 1: Trends in incident cases of NSCLC, 2018–27
Figure 2: Overview of pipeline drugs for NSCLC in the US
Figure 3: Pipeline drugs for NSCLC, by company
Figure 4: Pipeline drugs for NSCLC, by drug type
Figure 5: Pipeline drugs for NSCLC, by classification
Figure 6: Probability of success in the NSCLC pipeline
Figure 7: Clinical trials in NSCLC
Figure 8: Top 10 drugs for clinical trials in NSCLC
Figure 9: Top 10 companies for clinical trials in NSCLC
Figure 10: Trial locations in NSCLC
Figure 11: NSCLC trials status
Figure 12: NSCLC trials sponsors, by phase
Figure 13: The publisher’s drug assessment summary for NSCLC
Figure 14: Market dynamics in NSCLC
Figure 15: Future trends in NSCLC
Figure 16: Ilaris for NSCLC (March 9, 2021): Phase III - CANOPY-2
Figure 17: Keytruda for NSCLC (January 29, 2021): Phase III - KEYNOTE-598
Figure 18: Repotrectinib for NSCLC (January 29, 2021): Phase I/II - TRIDENT-1
Figure 19: AMG 510 for NSCLC (January 28, 2021): Phase I/II - CodeBreaK 100
Figure 20: Amivantamab for NSCLC (January 28, 2021): Phase I - CHRYSALIS (Advanced NSCLC)
Figure 21: TAK-788 for NSCLC (January 28, 2021): Phase I/II - EXCLAIM
Figure 22: Poziotinib for NSCLC (December 22, 2020): Phase II - ZENITH20 (EGFR or HER2 Exon 20 Mut.)
Figure 23: Nerlynx for NSCLC (November 5, 2020): Phase II - SUMMIT Basket (HER2mut, EGFRmut)
Figure 24: Vopratelimab for NSCLC (November 2, 2020): Phase II - EMERGE (w/Ipilimumab)
Figure 25: MK-1308 for NSCLC (October 16, 2020): Phase I/II - w/Pembrolizumab
Figure 26: Opdivo for NSCLC (October 7, 2020): Phase III - CheckMate-816
Figure 27: Keytruda for NSCLC (September 21, 2020): Phase III - KEYNOTE-024 (1L Monotherapy)
Figure 28: Libtayo for NSCLC (September 21, 2020): Phase III - EMPOWER-Lung 1 (1st Line)
Figure 29: AMG 510 for NSCLC (September 20, 2020): Phase I/II - CodeBreaK 100
Figure 30: Lorbrena for NSCLC (September 19, 2020): Phase III - CROWN (vs. Crizotinib)
Figure 31: Tagrisso for NSCLC (September 19, 2020): Phase III - ADAURA
Figure 32: U3-1402 for NSCLC (September 18, 2020): Phase I - A-U102
Figure 33: Repotrectinib for NSCLC (August 19, 2020): Phase I/II - TRIDENT-1
Figure 34: Lorbrena for NSCLC (August 5, 2020): Phase III - CROWN (vs. Crizotinib)
Figure 35: Opdivo for NSCLC (August 3, 2020): Phase III - TASUKI-52
Figure 36: Poziotinib for NSCLC (July 27, 2020): Phase II - ZENITH20 (EGFR or HER2 Exon 20 Mut.)
Figure 37: SAR408701 for NSCLC (May 31, 2020): Phase I/II - Advanced Solid Tumors
Figure 38: Tagrisso for NSCLC (May 31, 2020): Phase III - ADAURA
Figure 39: Enhertu for NSCLC (May 29, 2020): Phase II - DESTINY-Lung01
Figure 40: Sym015 NSCLC (May 29, 2020): Phase I/II - Safety (Anti-MET)
Figure 41: Tepmetko for NSCLC (May 29, 2020): Phase II - VISION (Adenocarcinoma)
Figure 42: Tabrecta for NSCLC (May 14, 2020): Phase II - GEOMETRY mono-1
Figure 43: Enhertu for NSCLC (May 13, 2020): Phase II - DESTINY-Lung01
Figure 44: Opdivo for NSCLC (May 13, 2020): Phase III - CheckMate-9LA (Stage IV, w/Ipilimumab)
Figure 45: Tagrisso for NSCLC (May 13, 2020): Phase III - ADAURA
Figure 46: Libtayo for NSCLC (April 27, 2020): Phase III - EMPOWER-Lung 1 (1st Line)
Figure 47: Tedopi for NSCLC (April 1, 2020): Phase III - ATALANTE-1
Figure 48: Key upcoming events in NSCLC (1 of 4)
Figure 49: Key upcoming events in NSCLC (2 of 4)
Figure 50: Key upcoming events in NSCLC (3 of 4)
Figure 51: Key upcoming events in NSCLC (4 of 4)

LIST OF TABLES
Table 1: Five-year survival rates of lung cancer, by stage at diagnosis
Table 2: Non-small cell lung cancer staging and corresponding TNM classifications
Table 3: Preferred branded first-line treatment regimens for patients with Stage IV EGFR+ NSCLC
Table 4: Preferred branded treatment regimens for patients who progress on first- and second-generation EGFR TKIs
Table 5: Preferred branded first- and second-line treatment regimens for patients with Stage IV ALK+ NSCLC
Table 6: Preferred treatment regimens for patients with Stage IV ROS1+ NSCLC
Table 7: Preferred treatment regimens for patients with Stage IV BRAF V600E mutated NSCLC
Table 8: Preferred treatment regimens for patients with Stage IV NSCLC and a MET exon 14 skipping mutation
Table 9: Preferred treatment regimens for patients with Stage IV RET+ NSCLC
Table 10: Preferred treatment regimens for patients with Stage IV NTRK+ NSCLC
Table 11: Preferred branded first-line treatment regimens for patients with advanced NSCLC and PD-L1+ TPS ≥50%
Table 12: Preferred branded first-line treatment regimens for patients with advanced NSCLC and PD-L1+ TPS ≥1–49%
Table 13: Preferred branded first-line treatment regimens for patients with advanced NSCLC
Table 14: Preferred branded second-line or later treatment regimens for patients with metastatic NSCLC
Table 15: Incident cases of NSCLC, 2018–27
Table 16: Incident cases of NSCLC, by gender, 2018
Table 17: Marketed drugs for NSCLC
Table 18: Pipeline drugs for NSCLC in the US
Table 19: Historical global sales, by drug ($m), 2015–19
Table 20: Forecasted global sales, by drug ($m), 2021–25
Table 21: Tecentriq for NSCLC (March 21, 2021)
Table 22: Ilaris for NSCLC (March 9, 2021)
Table 23: Keytruda for NSCLC (January 29, 2021)
Table 24: Repotrectinib for NSCLC (January 29, 2021)
Table 25: AMG 510 for NSCLC (January 28, 2021)
Table 26: Amivantamab for NSCLC (January 28, 2021)
Table 27: TAK-788 for NSCLC (January 28, 2021)
Table 28: Bintrafusp Alfa for NSCLC (January 19, 2021)
Table 29: Poziotinib for NSCLC (December 22, 2020)
Table 30: Keytruda for NSCLC (November 9, 2020)
Table 31: Nerlynx for NSCLC (November 5, 2020)
Table 32: Vopratelimab for NSCLC (November 2, 2020)
Table 33: MRTX849 for NSCLC (October 25, 2020)
Table 34: MK-1308 for NSCLC (October 16, 2020)
Table 35: Opdivo for NSCLC (October 7, 2020)
Table 36: AMG 510 for NSCLC (October 5, 2020)
Table 37: Keytruda for NSCLC (September 21, 2020)
Table 38: Libtayo for NSCLC (September 21, 2020)
Table 39: AMG 510 for NSCLC (September 20, 2020)
Table 40: Amivantamab for NSCLC (September 20, 2020)
Table 41: Lorbrena for NSCLC (September 19, 2020)
Table 42: Tagrisso for NSCLC (September 19, 2020)
Table 43: U3-1402 for NSCLC (September 18, 2020)
Table 44: CLN-081 for NSCLC (September 17, 2020)
Table 45: Lenvima for NSCLC (September 17, 2020)
Table 46: Repotrectinib for NSCLC (August 19, 2020)
Table 47: Ensartinib for NSCLC (August 8, 2020)
Table 48: Lorbrena for NSCLC (August 5, 2020)
Table 49: Opdivo for NSCLC (August 3, 2020)
Table 50: Poziotinib for NSCLC (July 27, 2020)
Table 51: SAR408701 for NSCLC (May 31, 2020)
Table 52: Tagrisso for NSCLC (May 31, 2020)
Table 53: Enhertu for NSCLC (May 29, 2020)
Table 54: Opdivo for NSCLC (May 29, 2020)
Table 55: Sym015 for NSCLC (May 29, 2020)
Table 56: Tagrisso for NSCLC (May 29, 2020)
Table 57: Tepmetko for NSCLC (May 29, 2020)
Table 58: Tabrecta for NSCLC (May 14, 2020)
Table 59: Enhertu for NSCLC (May 13, 2020)
Table 60: Opdivo for NSCLC (May 13, 2020)
Table 61: Tagrisso for NSCLC (May 13, 2020)
Table 62: Tiragolumab for NSCLC (May 13, 2020)
Table 63: Libtayo for NSCLC (April 27, 2020)
Table 64: Tagrisso for NSCLC (April 10, 2020)
Table 65: Tedopi for NSCLC (April 1, 2020)
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