ASCO Annual Meeting
ASCO Annual Meeting
Perspective from Razelle Kurzrock, MD
Perspective from Sumanta K. Pal, MD
June 04, 2016
2 min read

Off-label therapies show benefit for patients with advanced, mutated cancers

Perspective from Razelle Kurzrock, MD
Perspective from Sumanta K. Pal, MD
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CHICAGO — Patients with nine different tumor types benefited from targeted therapies administered outside of current drug indications, according to the results of a basket study presented at the ASCO Annual Meeting.

The researchers intend to expand cohorts of patients with HER-2–amplified colorectal cancer, bladder cancer and biliary cancer, as well as BRAF–mutated lung cancer, based on the observed outcomes.

John Hainsworth

John D. Hainsworth

“An increasing number of targeted agents for advanced cancer are approved now based on the presence of molecular abnormalities in the cancers,” John D. Hainsworth, MD, senior investigator at Sarah Cannon Research Institute in Nashville, Tennessee, said during a press conference. “Major successes in this area include HER-2–targeted treatment for HER-2–positive breast cancer and BRAF–targeted treatment for melanoma. We have known, though, that the same mutations are found in a wide variety of other cancers, although at a lower incidence. It is difficult to test how efficient these same treatments are, due to the difficulty of identifying the patient population.”

The MyPathway study included data from 129 patients with advanced solid tumors and no available curative therapy, whose tumors harbored the following alterations:

  • HER-2 amplification (n = 53), mutation (n = 23), both (n = 5) or RBMS-NRG1 fusion (n = 1);
  • BRAF V600E (n = 18) or other (n = 15);
  • Hedgehog (Hh) PTCH1 (n =7) or SMO (n = 1); or
  • EGFR (n = 6).

Patients enrolled in the trial had a median of three prior lines of therapy (median, 0-10).

The researchers evaluated the use of therapies targeting these alterations, including trastuzumab (Herceptin, Genentech) and pertuzumab (Perjeta, Genentech) for patients with HER-2 amplification; vemurafenib (Zelboraf, Genentech) for patients with BRAF alterations; vismodegib (Erivedge, Genentech) for patients with Hh alterations; and erlotinib (Tarceva; Genentech, Astellas) for patients with EGFR mutations.

Investigator-assessed response rate within the tumor-pathway cohort served as the study’s primary endpoint.

Eleven patients had insufficient follow-up data and were not included.

Twenty-nine patients achieved a partial response or complete response, including one complete response achieved by a patient with HER-2–amplified colorectal cancer.

Other cohorts that experienced responses included HER-2–amplified bladder cancer (n = 3) and biliary cancer (lung cancer, n = 2; salivary gland cancer, n = 1); three patients with BRAF–mutated lung cancer; one case each of BRAF–mutated ovarian cancer, cancer of unknown primary origin, colon cancer, pancreatic cancer, and head and neck cancer; and two patients with Hh alterations (squamous cell carcinoma, n = 1; cancer of unknown primary origin, n = 1).

Three patients with BRAF–mutated lung cancer have achieved objective responses, and two achieved stable disease. Based on these data, the researchers will expand this cohort.

Current response durations have continued up to 11 months. Fourteen responding patients have progressed, at a median of 6 months after treatment (range, 3-14).

The study design allows for the accrual of up to 500 patients, with expansions stopped for groups that exhibit low benefit and expanded for those who demonstrate efficacy. The researchers further intend to incorporate new agents targeted additional molecular alterations.

“I think we have shown that this trial design is feasible, with patients selected based on molecular abnormalities in their cancers rather than on their primary tumor type or primary site,” Hainsworth said. “It offers opportunities for patients with these molecular abnormalities. The MyPathway trial continues to accrue patients, and as of last week we have 200 patients accrued so far.” – by Cameron Kelsall


Hainsworth JD, et al. Abstract LBA11511. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.

Disclosure: Genentech funding this study. Hainsworth reports institutional research funding from Astellas Pharma, AstraZeneca, Celgene, Genentech, Johnson & Johnson, Eli Lilly and Novartis. Please see the abstract for a list of all other researchers’ relevant financial disclosures.