Afatinib Improves Progression-Free Survival vs Erlotinib in Second-Line Treatment of Advanced Squamous Cell Carcinoma of the Lung

“In the phase III LUX-Lung 8 trial reported in The Lancet Oncology, Soria et al found that the irreversible ErbB-family inhibitor afatinib (Gilotrif) significantly improved progression-free and overall survival vs the EGFR tyrosine kinase inhibitor erlotinib as second-line treatment in patients with stage IIIB or IV squamous cell carcinoma of the lung who had disease progression after four or more cycles of platinum-based chemotherapy.

“In this open-label trial, 795 patients from 23 countries were randomly assigned between March 2012 and January 2014 to receive afatinib at 40 mg/d (n =398) or erlotinib at 150 mg/d (n = 397). The primary endpoint was progression-free survival on independent central review in the intent-to-treat population…

“The investigators concluded: ‘The significant improvements in progression-free survival and overall survival with afatinib compared with erlotinib, along with a manageable safety profile and the convenience of oral administration suggest that afatinib could be an additional option for the treatment of patients with squamous cell carcinoma of the lung.’ “


Palbociclib's Role in Endocrine-Resistant Breast Cancer

“Palbociclib (Ibrance, Pfizer), the first CDK4/6 inhibitor to be approved for the treatment of breast cancer, has been welcomed by experts for its role in improving outcomes in patients with endocrine-resistant breast cancer.

“The drug should a significant improvement in progression-free survival (PFS) when it was added to fulvestrant (Faslodex, AstraZeneca) in the phase 3 PALOMA 3 trial, as reported recently by Medscape Medical News. The addition of palbociclib to fulvestrant increased median PFS to 9.2 months in patients with estrogen receptor (ER)–positive/HER2-negative endocrine-resistant breast cancer compared with 3.8 months in the placebo-fulvestrant group (P < .001).

“The overall survival data are still immature.

“The full results have now been published in print in the July 16 issue of the New England Journal of Medicine.


Pembrolizumab Increases Progression-Free Survival vs Chemotherapy in Ipilimumab-Refractory Advanced Melanoma

“In a randomized phase II KEYNOTE-002 trial reported in The Lancet Oncology, Ribas et al found that treatment with the anti–PD-1 antibody pembrolizumab (Keytruda) prolonged progression-free survival vs investigator-choice chemotherapy in patients with advanced melanoma progressing on ipilimumab (Yervoy) and, if BRAF V600 mutant–positive, a BRAF or MEK inhibitor.

“The open-label trial included 540 patients from 12 countries with progressive disease within 24 weeks after two or more ipilimumab doses and, if BRAF V600 mutant–positive, previous treatment with a BRAF or MEK inhibitor or both. Patients were randomly assigned 1:1:1 between November 2012 and November 2013 to receive pembrolizumab 2 mg/kg (n = 180) or 10 mg/kg (n = 181) every 3 weeks or investigator-choice chemotherapy (n = 179, including 42 to paclitaxel plus carboplatin, 28 to paclitaxel, 13 to carboplatin, 45 to dacarbazine, and 43 to temozolomide)…

“The investigators concluded: ‘These findings establish pembrolizumab as a new standard of care for the treatment of ipilimumab-refractory melanoma.’ “


Adding Everolimus to First-Line Trastuzumab-Paclitaxel Does Not Increase Progression-Free Survival in HER2-Positive Breast Cancer

“In the phase III BOLERO-1 trial, reported in The Lancet Oncology, Hurvitz et al found that the addition of the mTOR inhibitor everolimus (Afinitor) to trastuzumab (Herceptin)-paclitaxel did not significantly increase progression-free survival among patients with HER2-positive advanced breast cancer. A 7-month prolongation in progression-free survival was observed with everolimus among patients with hormone receptor–negative disease.”


Statins at Start of Androgen Deprivation Therapy Increase Treatment Efficacy

“Statin use has been associated with improved outcome in prostate cancer. In a study reported in JAMA Oncology, Harshman et al found that statin use at the time of initiation of androgen-deprivation therapy was associated with prolonged time to progression during androgen-deprivation therapy in men with hormone-sensitive prostate cancer. The potential mechanism of this effect may be statin competitive inhibition of dehydroepiandrosterone sulfate (DHEAS) uptake.

“Androgen-deprivation therapy for biochemical or metastatic recurrence or new metastatic disease between January 1996 and November 2013 showed that 283 men (31%) were taking statins at the start of androgen-deprivation therapy. After a median follow-up of 5.8 years, 644 patients (70%) had disease progression while receiving androgen-deprivation therapy, with a median time to progression during androgen-deprivation therapy of 20.3 months. Median time to progression was 27.5 months (95% confidence interval [CI] = 21.1–37.7 months) in statin users vs 17.4 months (95% CI = 14.9–21.1 months) in nonusers (P < .001).”


Breast Cancer Trial Results Spin a Cautionary Tale

“In the care of patients with metastatic breast cancer, the next new thing is the same old thing: paclitaxel (multiple brands).

“Results of the CALGB 40502/NCCTG N063H (Alliance) trial, first reported at the American Society of Clinical Oncology annual meeting in 2012 and published online June 8 in the Journal of Clinical Oncology, show that patients with advanced breast cancer had better median progression-free survival (PFS) with once-weekly paclitaxel than with ixabepilone (Ixempra, Bristol-Myers Squibb Company), a newer agent.

“In the third arm of the trial, paclitaxel was equivalent in its effect on PFS to its newer, more water-soluble cousin, nanoparticle alubimun-bound paclitaxel (nab-paclitaxel), and plain old paclitaxel was less toxic than either of its comparators.”


Alectinib Promising in ALK-Positive Advanced NSCLC

“The ALK and RET inhibitor alectinib yielded good response rates and was very well tolerated in a phase II trial of patients with advanced, ALK-positive non–small-cell lung cancer (NSCLC; abstract 8008). Results were presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 29 to June 2, in Chicago.

“Crizotinib is currently the standard-of-care for advanced, treatment-naive ALK-positive NSCLC. ‘However, the median progression-free survival (PFS) for these patients on crizotinib is under 12 months,’ said Sai-Hong Ignatius Ou, MD, PhD, of the UC Irvine Medical Center in California. ‘This is in part due to development of ALK mutations that are resistant to crizotinib.’

“Alectinib is a next-generation inhibitor that is highly selective for ALK and RET; as an ALK inhibitor, Ou said, it is approximately five times as potent as crizotinib. It can inhibit the majority of clinically relevant acquired ALK mutations.”


Melanoma at ASCO 2015: Immunotherapy Continues to Make Headlines


The biggest news in melanoma treatment from the 2015 American Society of Clinical Oncology (ASCO) annual meeting was undoubtedly the report from a large, phase III, randomized clinical trial that compared a combination of two ‘checkpoint inhibitor’ drugs—nivolumab (Opdivo) and ipilimumab (Yervoy)—with the same drugs given alone.

In the CheckMate-067 trial, 945 previously untreated patients with unresectable stage III or IV melanoma were assigned to Opdivo alone, Opdivo plus Yervoy, or Yervoy alone. Continue reading…


Immunotherapy Combo Cuts Melanoma Death Risk

“An immunotherapy combination for untreated melanoma reduced the risk of death or progression by more than half as compared with a drug currently used as a standard of care, a large randomized trial showed.

“Patients treated with nivolumab (Opdivo) and ipilimumab (Yervoy) had a median progression-free survival (PFS) of 11.5 months compared with 2.9 months for ipilimumab alone and 6.9 months with nivolumab monotherapy. Median PFS with the combination and with nivolumab alone increased to 14 months — more than four times greater than the PFS of patients who received only ipilimumab — among patients whose tumors tested positive for programmed death receptor ligand 1 (PD-L1), the target of nivolumab.

“The PFS improvement came at a price of increased toxicity, as grade 3/4 adverse events occurred twice as often with the combination as with ipilimumab monotherapy, but even patients who discontinued treatment because of side effects did better with the combination, as reported here at the American Society of Clinical Oncology meeting.”