2015 Review of Newly Approved Oncologic Therapies

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Patrick Medina, PharmD

Monique Giordana, PharmD, BCOP

There definitely is some difference in side effects between [sonidegib] and vismodegib, which does not have this big increase in creatinine kinase.

—Patrick Medina, PharmD
This is quite remarkable improvement [in response rate with nivolumab]. We have never seen these types of response rates in melanoma.

—Monique Giordana, PharmD, BCOP

Over the past year or so, a host of new agents were approved for the treatment of patients with various types of cancer (see related article on page 1). Patrick Medina, PharmD, of the University of Oklahoma College of Pharmacy, Oklahoma City, and
Monique Giordana, PharmD, BCOP, of Regions Hospital, St. Paul, Minnesota, brought listeners up to date on many of these newly approved agents at the 3rd Annual JADPRO (Journal of the Advanced Practitioner in Oncology) Live at APSHO (Advanced Practitioner Society for Hematology and Oncology) conference.1 Approximately 700 nurse practitioners, physician assistants, pharmacists, clinical nurse specialists, and other health-care professionals assembled in Phoenix, Arizona, to attend this conference.

Pathway Inhibitors

Two molecular pathway inhibitors were among the agents featured: sonidegib (Odomzo) and olaparib (Lynparza). Approved in July 2015 for adults with locally advanced basal cell carcinoma that has recurred after surgery or radiation therapy or for those who are not candidates for surgery or radiation therapy, sonidegib is a hedgehog signaling pathway inhibitor and the second agent in this class of drugs. Supporting data for this indication are from the randomized phase II BOLT trial.2

Among the adverse events reported with this oral agent are muscle spasms, fatigue, musculoskeletal pain, decreased weight and appetite, abdominal pain, and pruritus. “The majority of patients that you put on this drug will get this muscle pain,” stated Dr. Medina.

The drug should be withheld for severe or intolerable musculoskeletal adverse reactions, so serum creatinine kinase elevation should be checked periodically. Dr. Medina continued: “This is a fairly unique side effect for this class of drugs, so there definitely is some difference in side effects between this and vismodegib [Erivedge], which is not associated with this big increase in creatinine kinase.”

Approved in December 2014, the PARP inhibitor olaparib is indicated for monotherapy in patients with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. According to the clinical trial on which this indication is based,3 responses to olaparib were observed across different tumor types with these mutations. With few active agents for ovarian cancer, Dr. Giordana called this an “exciting” drug for this patient population.

Among the adverse events associated with olaparib are anemia, nausea, vomiting, dyspepsia, upper respiratory infection, arthralgia, and rash. “Although anemia is the biggest side effect, arthralgia can be troublesome for patients,” remarked Dr. Giordana.


In late 2014, two anti–programmed cell death protein 1 (anti–PD-1) agents—nivolumab (Opdivo) and pembrolizumab (Keytruda)—changed the therapeutic landscape for those with unresectable or metastatic melanoma; and as of late 2015, both agents have expanded their indication to use in the treatment of non–small cell lung cancer (NSCLC).

The original indication for nivolumab is for unresectable or metastatic melanoma and disease progression after ipilimumab (Yervoy) and if BRAF V600 mutation–positive, a BRAF inhibitor, based on the findings of the CheckMate-037 trial.4 Expanded indications now include both squamous5 and nonsquamous6 NSCLC, based on data from CheckMate-017 and CheckMate-057, respectively. In addition, the most common immune-therapy adverse events reported with these agents are fatigue, diarrhea, and skin toxicity with rash.

Dr. Giordana focused on the 32% objective response rate with nivolumab in the CheckMate-037 trial. “Back when ipilimumab was approved a few years back,” she remarked, “the response rate was around 11%. This is quite remarkable improvement. We have never seen these types of response rates in melanoma.” Furthermore, Dr. Giordana hinted at the “super exciting data” emerging with the combination of nivolumab and ipilimumab.

The original indication for pembrolizumab was unresectable or metastatic melanoma and disease progression following ipilimumab and if BRAF V600 mutation–positive, a BRAF inhibitor, based on data from the Keynote-001 trial.7 As with nivolumab, more recent data now support its use for squamous and nonsquamous NSCLC.8 According to more recent phase III study data with the combination of nivolumab and ipilimumab in unresectable or metastatic melanoma, Dr. Giordana noted that “we are seeing response rates of 60%.”

Other Agents

Drs. Medina and Giordana featured several other agents during their presentation, a few of which are briefly mentioned here:

Gefitinib (Iressa): Reapproved in July 2015, this epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor is indicated only for first-line treatment of patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations.

Dinutuximab (Unituxin): Approved in March 2015, this chimeric GD2 antibody is indicated in combination with granulocyte-macrophage colony-stimulating factor (Leukine), interleukin 2 (Proleukin), and 13-cis-retinoic acid for treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to prior first-line therapy. Dr. Medina called this “huge news in the pediatric world,” although she admitted it is an “inpatient nightmare” to deliver, as it causes severe neuropathic pain for patients.

Lenvatinib (Lenvima): Approved in February 2015, this inhibitor of vascular endothelial growth factor receptor is indicated for treatment of locally recurrent or metastatic progressive, radioactive iodine–refractory differentiated thyroid cancer. According to Dr. Medina, “it appears to be a drug that is highly efficacious in this somewhat niche population.”

Palbociclib (Ibrance): Approved in February 2015, this cyclin-dependent kinase 4 and 6 inhibitor is indicated in combination with letrozole for treatment of postmenopausal women with estrogen receptor–positive, HER2-negative metastatic breast cancer as initial endocrine-based therapy. Although Dr. Medina admitted this treatment was associated with a “pretty high rate of neutropenia,” he added, “this drug has implications in a lot of tumors, not just breast cancer.” ■

Disclosure: Drs. Medina and Giordana reported no potential conflicts of interest.


1. Medina P, Giordana M: Review of newly approved oncologic therapies: 2014–2015. JADPRO Live at APSHO. General Session. Presented November 6, 2015.

2. Migden MR, Guminski A, Gutzmer R, et al: Treatment with two different doses of sonidegib in patients with locally advanced or metastatic basal cell carcinoma (BOLT): A multicentre, randomised, double-blind phase 2 trial. Lancet Oncol 16:716-728, 2015.

3. Kaufman B, Shapira-Frommer R, Schmutzler RK, et al: Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol 33:244-250, 2015.

4. Weber JS, D’Angelo SP, Minor D, et al: Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): A randomised, controlled, open-label, phase 3 trial. Lancet Oncol 16:375-384, 2015.

5. Spigel DR, Reckamp KL, Rizvi NA, et al: A phase III study (CheckMate 017) of nivolumab (anti-programmed death-1 [PD-1]) vs docetaxel in previously treated advanced or metastatic squamous cell non-small cell lung cancer. 2015 ASCO Annual Meeting. Abstract 8009. Presented May 29, 2015.

6. Paz-Ares L, Horn L, Borghaei H, et al: Phase III, randomized trial (CheckMate 057) of nivolumab versus docetaxel in advanced non-squamous cell non-small cell lung cancer. 2015 ASCO Annual Meeting. Abstract LBA109. Presented May 29, 2015.

7. Robert C, Ribas A, Wolchok JD, et al: Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: A randomised dose-comparison cohort of a phase 1 trial. Lancet 384:1109-1117, 2014.

8. Bustamante Alvarez JG, González-Cao M, Karachaliou N, et al: Advances in immunotherapy for treatment of lung cancer. Cancer Biol Med 12:209-222, 2015.