ALCHEMIST: Bringing genomic discovery and targeted therapies to early‐stage lung cancer

Gerber, David E.; Oxnard, GR; Govindan, Ramaswamy

doi:10.1002/cpt.91

Cited by 46 publications

(30 citation statements)

References 5 publications

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“…The disease free survival rate of 90 % at 2 years (97 % stage 1, 73 % stage 2, and 92 % stage 3) was considered superior to historical genotypematched controls; most recurrences happened over 12 months after stopping treatment [27]. ALCHEMIST is a phase III trial initiated in 2014 with the goal of exploring the role of molecularly targeted therapy in the adjuvant setting; unlike previous adjuvant trials, all patients will undergo centralized molecular testing prior to enrollment [28]. Resected tumor specimens will be tested for both ALK rearrangements and EGFR mutations; patients harboring one of these genetic alterations will then be referred into either the ALCHEMIST-ALK or ALCHEMIST-EGFR trials, where they will receive crizotinib or erlotinib vs. placebo, respectively, after completing standard adjuvant chemotherapy.…”

Section: First-generation Egfr Inhibitorsmentioning

confidence: 99%

Generations of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: Perils and Progress

Castellanos

Horn

2015

Curr. Treat. Options in Oncol.

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Epidermal growth factor receptor (EGFR) mutations have been detected in approximately 10 % of North American patients diagnosed with non-small cell lung cancer (NSCLC). Approximately 90 % of these mutations are exon 19 deletions or exon 21 L858R point mutations. First- and second-generation EGFR tyrosine kinase inhibitors (TKIs) are approved as first-line therapy based on clinical trials demonstrating superior response rates, progression free survival (PFS), and overall survival (OS) compared to chemotherapy in patients with EGFR mutation-positive NSCLC treated with an EGFR TKI prior to chemotherapy. However, the majority of patients treated with an EGFR TKI develop resistance to therapy within about 12 months, approximately 50 % of patients due to a second site mutation, the T790M mutation occurring within exon 20. At the time of progression, the EGFR TKI is most commonly discontinued and a different systemic therapy is initiated. However, oncogene addiction persists and recent exciting data with third-generation EGFR TKIs suggests that acquired resistance may be surmountable. The newest EGFR TKIs have shown activity against EGFR-mutant NSCLC after progression on first-generation TKIs, including those with T90M, while sparing wild-type EGFR and hence appear to be both well tolerated and efficacious. At this time, it appears that third-generation EGFR TKIs are effective following first-generation therapy, and determining the most appropriate sequence to maximize overall survival is a matter of ongoing investigation. As the arsenal of active agents in EGFR mutant NSCLC grows, future research into potential combinations, optimal timing, and resistance mechanisms of these new treatments, as well as their possible role in the adjuvant, post-chemoradiation, and neoadjuvant settings holds great promise for this group of patients.

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Section: First-generation Egfr Inhibitorsmentioning

confidence: 99%

Generations of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: Perils and Progress

Castellanos

Horn

2015

Curr. Treat. Options in Oncol.

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“…Example umbrella trials include FOCUS4 [27], ALCHEMIST [28–29], and LUNG-MAP [30–31]. Like the umbrella trial, a Bayesian marker-adaptive design (Figure 1f) may include multiple therapies and molecular subgroups.…”

Section: Biomarker-based Designs Overviewmentioning

confidence: 99%

Precision oncology: A new era of cancer clinical trials

Renfro

Mandrekar

2017

Cancer Letters

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Traditionally, site of disease and anatomic staging have been used to define patient populations to be studied in individual cancer clinical trials. In the past decade, however, oncology has become increasingly understood on a cellular and molecular level, with many cancer subtypes being described as a function of biomarkers or tumor genetic mutations. With these changes in the science of oncology have come changes to the way we design and perform clinical trials. Increasingly common are trials tailored to detect enhanced efficacy in a patient subpopulation, e.g., patients with a known biomarker value or whose tumors harbor a specific genetic mutation. Here, we provide an overview of traditional and newer biomarker-based trial designs, and highlight lessons learned through implementation of several ongoing and recently completed trials.

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“…Duration of treatment with targeted therapies will be up to 2 years. Planned enrollment for these trials are 410 and 378 patients, respectively, with OS as a primary endpoint (80).…”

Section: Role Of Targeted and Immune Therapies In Earlier Stagesmentioning

confidence: 99%

Prognostic and predictive biomarkers post curative intent therapy

Feldman¹,

Kim²

2017

Ann. Transl. Med.

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Large-scale screening trials have demonstrated that early diagnosis of lung cancer results in a significant reduction in lung cancer mortality. Despite improvements in detecting more lung cancers at early stages, the 5-year survival rates of lung cancers diagnosed before widespread disease is only 30-50%.High rates of recurrence, despite early diagnosis, suggest the need to improve treatment strategies based on the likelihood of recurrence in patient subsets, as well as explore the role of predictive markers for therapy selection in the adjuvant setting. In the era of personalized medicine, there have been a wide array of molecular alterations and signatures studied for their potential prognostic and predictive utility, however most have failed to translate into clinical tools. This review will discuss progress made in clinical management of lung cancer, and recent progress in the development of patient selection tools for the refinement of early stage lung cancers.

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ALCHEMIST: Bringing genomic discovery and targeted therapies to early‐stage lung cancer

Cited by 46 publications

References 5 publications

Generations of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: Perils and Progress

Generations of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: Perils and Progress

Precision oncology: A new era of cancer clinical trials

Prognostic and predictive biomarkers post curative intent therapy

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