ASCO Annual Meeting

ASCO Annual Meeting

Perspective from Charu Aggarwal, MD, MPH
Perspective from John Heymach, MD, PhD
Perspective from Nicholas C. Rohs, MD
Source:

Herbst RS, et al. Abstract LBA5. Scheduled for presentation at: ASCO20 Virtual Scientific Program; May 29-31, 2020.


Disclosures: AstraZeneca funded this study. Herbst reports a leadership role with Jun Shi Pharmaceuticals; research funding from AstraZeneca, Eli Lilly, Genentech/Roche and Merck; and consultant/advisory roles with AbbVie, ARMO Biosciences, AstraZeneca, Biodesix, Bolt Biotherapeutics, Bristol-Myers Squibb, Eli Lilly, EMD Serono, Genentech/Roche, Genmab, Halozyme, Heat Biologics, IMAB Biopharma, Immunocore, Infinity Pharmaceuticals, Jun Shi Pharmaceuticals, Loxo Oncology, Merck, Midas Health Analytics, Mirati Therapeutics, Nektar Therapeutics, Neon Therapeutics, NextCure, Novartis, Pfizer, Sanofi, Seattle Genetics, Shire, Spectrum Pharmaceuticals, Symphogen, Takeda, Tesaro and Tocagen. Please see the abstract for all other researchers’ relevant financial disclosures.
May 29, 2020
6 min read
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Adjuvant osimertinib extends DFS in EGFR-mutated NSCLC

Perspective from Charu Aggarwal, MD, MPH
Perspective from John Heymach, MD, PhD
Perspective from Nicholas C. Rohs, MD
Source:

Herbst RS, et al. Abstract LBA5. Scheduled for presentation at: ASCO20 Virtual Scientific Program; May 29-31, 2020.


Disclosures: AstraZeneca funded this study. Herbst reports a leadership role with Jun Shi Pharmaceuticals; research funding from AstraZeneca, Eli Lilly, Genentech/Roche and Merck; and consultant/advisory roles with AbbVie, ARMO Biosciences, AstraZeneca, Biodesix, Bolt Biotherapeutics, Bristol-Myers Squibb, Eli Lilly, EMD Serono, Genentech/Roche, Genmab, Halozyme, Heat Biologics, IMAB Biopharma, Immunocore, Infinity Pharmaceuticals, Jun Shi Pharmaceuticals, Loxo Oncology, Merck, Midas Health Analytics, Mirati Therapeutics, Nektar Therapeutics, Neon Therapeutics, NextCure, Novartis, Pfizer, Sanofi, Seattle Genetics, Shire, Spectrum Pharmaceuticals, Symphogen, Takeda, Tesaro and Tocagen. Please see the abstract for all other researchers’ relevant financial disclosures.
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Adjuvant osimertinib significantly prolonged DFS for patients with EGFR-mutated non-small cell lung cancer, according to results of the randomized phase 3 ADAURA trial scheduled for presentation during the ASCO20 Virtual Scientific Program.

Osimertinib (Tagrisso, AstraZeneca) is the first targeted agent in a global trial to confer statistically significant and clinically meaningful DFS improvement for this patient population.

“These are extraordinary results,” Roy S. Herbst, MD, PhD, chief of medical oncology at Yale Cancer Center and Smilow Cancer Hospital, as well as associate cancer center director for translational research at Yale Cancer Center, said during a presentation. “Adjuvant osimertinib provides a highly effective, practice-changing treatment for [these patients].”

Roy Herbst
Roy S. Herbst

Approximately one-third of patients with NSCLC present with early-stage disease, defined as stage I through stage IIIA. Surgery is the primary treatment for these patients. Adjuvant chemotherapy is standard for those with stage II or stage III disease, as well as for select patients with stage IB disease.

Adjuvant osimertinib significantly prolonged DFS for patients with EGFR-mutated non-small cell lung cancer compared with placebo.

Despite these treatments, 5-year recurrence rates range from 45% for patients with stage IB disease to 76% for those with stage III disease.

“Clearly, we need new therapies,” Herbst said.

Osimertinib — a third-generation, irreversible EGFR-directed tyrosine kinase inhibitor — is approved in the United States for first-line treatment of patients with metastatic NSCLC whose tumors harbor EGFR mutations. Prior studies showed superior efficacy with osimertinib compared with other EGFR TKIs for treatment-naive, EGFR-mutated advanced NSCLC.

The double-blind, multinational ADAURA trial evaluated the efficacy and safety of adjuvant osimertinib vs. placebo for patients with stage IB to stage IIIA EGFR-mutated NSCLC who underwent complete tumor resection and — if indicated — adjuvant chemotherapy.

The trial included 682 adults with primary nonsquamous disease. All patients had confirmed EGFR mutations and WHO performance status of 0 or 1, and all had undergone complete resection with full recovery.

Researchers randomly assigned 339 patients to osimertinib dosed at 80 mg once daily. The other 343 patients received placebo. Treatment continued for up to 3 years.

Treatment groups were balanced with regard to disease stage (stage IB, 31% each; stage II/IIIA, 69% each), sex (women, 68% for osimertinib vs. 72% for placebo), exon 19 deletion mutation (55% vs. 56%) and exon 21 L858R mutation (45% vs. 44%).

Investigators stratified their analysis by disease stage, mutation type and race (Asian vs. non-Asian).

Investigator-assessed DFS among patients with stage II or stage IIIA disease served as the primary endpoint. Secondary endpoints included DFS in the entire study population, OS and safety.

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The independent data monitoring committee recommended the trial be unblinded early due to efficacy.

Herbst reported results of an unplanned interim analysis, which showed osimertinib significantly improved DFS among patients with stage II to stage IIIA disease (median, not reached vs. 20.4 months; HR = 0.17; 95% CI, 0.12-0.23).

“This was much better than expected, and it certainly is something that will help our patients,” Herbst said.

Osimertinib also conferred a statistically significant DFS benefit in the overall study population (median, not reached vs. 28.1 months; HR = 0.21; 95% CI, 0.16-0.28).

“Even when you add the patients with earlier-stage disease, you still have curves that [have clear separation],” Herbst said. “The reduction in risk for disease progression is a little bit less because you have many patients with earlier disease but, nonetheless, this is a very positive [result] that suggests the drug will be useful for these patients, as well.”

Osimertinib-treated patients were more likely than those assigned placebo to be disease free at 2 years (stage II to stage IIIA disease, 90% vs. 44%; overall population, 89% vs. 53%).

Researchers observed the DFS benefit with osimertinib in all evaluated subgroups, including those based on age, sex, smoking status, race, disease stage, type of EGFR mutation and adjuvant chemotherapy receipt.

OS data were immature, with the majority (95.7%; n = 653) of patients still alive at the time of data cutoff. Of the 29 patients who died, 20 had been assigned placebo.

Median duration of treatment exposure was 22.3 months (range, 0-43) in the osimertinib group and 18.4 months (range, 0-48) in the placebo group.

Osimertinib appeared generally well-tolerated, exhibiting a safety profile consistent with prior reports.

The most common adverse events that occurred more frequently in the osimertinib group included diarrhea (46% vs. 19%), paronychia (25% vs. 1%), dry skin (23% vs. 6%), pruritis (19% vs. 9%), cough (18% vs. 17%), stomatitis (17% vs. 4%), nasopharyngitis (15% vs. 10%), decreased appetite (13% vs. 4%) and upper respiratory infection (13% vs. 9%).

Grade 3 or grade 4 adverse events were rare in the osimertinib group. They included diarrhea (2%), stomatitis (2%), decreased appetite (1%), paronychia (1%) and upper respiratory infection (1%).

Ten patients (3%) assigned osimertinib developed interstitial lung disease, but all cases were low grade.

Herbst described the trial as “a home run” that yielded “an important advance” in the form of a targeted therapy that can significantly delay recurrence after surgery.

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He closed his presentation by acknowledging his mentor, Isaiah Fidler, DVM, PhD, professor of cancer biology at The University of Texas MD Anderson Cancer Center, who died May 8.

“He taught me, and he taught all of us, that it is metastasis — the spread of tumor — that kills patients,” Herbst said. “Drugs such as this, based on biology [and] given to patients at the earliest possible time, can prevent those metastases and allow patients to live longer, with a better quality of life.” – by Mark Leiser

Reference:

Herbst RS, et al. Abstract LBA5. Scheduled for presentation at: ASCO20 Virtual Scientific Program; May 29-31, 2020.

Disclosure: AstraZeneca funded this study. Herbst reports a leadership role with Jun Shi Pharmaceuticals; research funding from AstraZeneca, Eli Lilly, Genentech/Roche and Merck; and consultant/advisory roles with AbbVie, ARMO Biosciences, AstraZeneca, Biodesix, Bolt Biotherapeutics, Bristol-Myers Squibb, Eli Lilly, EMD Serono, Genentech/Roche, Genmab, Halozyme, Heat Biologics, IMAB Biopharma, Immunocore, Infinity Pharmaceuticals, Jun Shi Pharmaceuticals, Loxo Oncology, Merck, Midas Health Analytics, Mirati Therapeutics, Nektar Therapeutics, Neon Therapeutics, NextCure, Novartis, Pfizer, Sanofi, Seattle Genetics, Shire, Spectrum Pharmaceuticals, Symphogen, Takeda, Tesaro and Tocagen. Please see the abstract for all other researchers’ relevant financial disclosures.