Are emerging targeted therapies poised to fill the significant unmet need of patients in the second and subsequent lines of therapy?

Treatment decisions for non-small-cell lung cancer (NSCLC) patients are increasingly based on personalized tumor-specific characteristics. It is now standard practice for patients with advanced NSCLC of nonsquamous-cell—particularly adenocarcinoma—histology to undergo testing for epidermal growth factor receptor (EGFR) mutations. While the first-generation EGFR tyrosine kinase inhibitors (TKIs), erlotinib (Genentech/Roche/Chugai/Astellas’s Tarceva) and gefitinib (AstraZeneca’s Iressa) have revolutionized the first-line treatment of NSCLC (EGFR-mutation-positive; previously treated), no targeted agents are currently approved in the second or subsequent- lines. Consequently, the outcome for patients with NSCLC (EGFR-mutation-positive; previously treated) remains bleak. Going forward, the market is expected to become increasingly competitive following the approval of the targeted second-generation and third-generation EGFR TKIs for NSCLC (EGFR-mutation-positive; previously treated). Despite this development, significant clinical and commercial opportunity remains for therapies that can provide greater survival benefits than current standards of care.

Questions Answered in This Report:

  • Improved overall survival and improved progression-free survival are key goals in the treatment of NSCLC (EGFR-mutation-positive; previously treated). What are the key primary and secondary clinical trial end points with which new therapies are evaluated? How do U.S. and European oncologists weight specific efficacy end-points and other drug attributes in their prescribing decisions for NSCLC (EGFR-mutation-positive; previously treated)?

  • Increased overall survival, delayed disease progression, and a lower rate of dermatological toxicity are key areas of unmet need for NSCLC (EGFR-mutation-positive; previously treated) according to the insights of surveyed U.S. and European oncologists. Which therapies in development for NSCLC (EGFR-mutation-positive; previously treated) are poised to fulfill these needs? What clinical and/or regulatory challenges must drug developers overcome in order to capitalize on these areas of unmet need? What degree of improvement over currently available therapies do surveyed U.S. MCO PDs seek from new therapies on key clinical attributes for which surveyed physicians indicate there is high unmet need?

  • Median overall survival and median progression-free survival are key drivers of physicians’ prescribing decisions and/or are the focus of drug development for new NSCLC (EGFR-mutation-positive; previously treated) therapies. What trade-offs across these and other clinical attributes are U.S. oncologists willing to make when considering the use of emerging therapies for the treatment of NSCLC (EGFR-mutation-positive; previously treated)? Based on the trade-offs in price and performance across key drug attributes that U.S. oncologists are willing to make, how do physician preference and prescribing likelihood vary across different target product profiles for NSCLC (EGFR-mutation-positive; previously treated)?

  • By 2022, CO-1686 and AP-26113 will emerge as joint gold-standard therapies in our Drug Comparator Model because of their superior clinical profile over the key current therapies we evaluated. On what clinical attributes are CO-1686 and AP-26113 most differentiated from their competitors? Which current therapies are at greatest risk of being replaced by CO-1686 and AP-26113?


Attributes included in conjoint analysis based assessment of target product profiles for NSCLC (EGFR-mutation-positive; previously treated):

- Median overall survival.

- Median progression-free survival.

- Overall response rate.

- Hematological toxicity: rate of grade 3/4 neutropenia.

- Dermatological toxicity: rate of all grades skin rash.

- Gastrointestinal toxicity: rate of all grades diarrhea.

- Price per 21-day cycle.

Attributes included in assessment of U.S. payers’ receptivity to new therapies for NSCLC (EGFR-mutation-positive; previously treated):

- Effect on median overall survival.

- Effect on progression-free survival.

- Incidence of grade 3/4 neutropenia.

- Incidence of all grades rash.

Physicians surveyed: 61 U.S. and 30 European oncologists.

Payers surveyed: 20 U.S. MCO PDs.

Comprehensive List of Therapies Included in Our Research and Modeling:

Current Therapies

- Pemetrexed (Eli Lilly’s Alimta)

- Docetaxel (Sanofi’s Taxotere, generics)

- Gemcitabine (Eli Lilly’s Gemzar) + cisplatin (generics)

- Pemetrexed (Eli Lilly’s Alimta) + cisplatin (generics)

- Paclitaxel (Bristol-Myers Squibb’s Taxol, generics) + carboplatin (generics) + bevacizumab (Genentech/Roche/Chugai’s Avastin)

Emerging Therapies

- Afatinib (Boehringer Ingelheim’s Gilotrif/Giotrif)

- Dacomitinib (Pfizer)

- CO-1686 (Clovis Oncology/Celgene)

- AP-26113 (Ariad Pharmaceuticals)

- Ganetespib (Synta Pharmaceuticals) + docetaxel (Sanofi’s Taxotere, generics)