Pembrolizumab New Option for First Line Treatment of Patients with Advanced Lung Cancer and High PD-L1 Expression

Excerpt:
“Pembrolizumab is set to become a new option for first line treatment of patients with advanced lung cancer and high PD-L1 expression, according to the results of the phase III KEYNOTE-024 trial presented at the ESMO 2016 Congress in Copenhagen and published in the New England Journal of Medicine.

“‘Pembrolizumab is a PD-1 antibody approved for second line treatment of patients with advanced non-small-cell lung cancer (NSCLC) and PD-L1 expression in their tumour cells,’ said lead author Professor Martin Reck, chief oncology physician, Department of Thoracic Oncology, Lung Clinic Grosshansdorf, Germany. ‘KEYNOTE-024 is the first phase III trial of pembrolizumab as first line treatment in patients with high PD-L1 expression, who represent 27-30% of those with advanced NSCLC.’ ”

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New Data Evaluating KEYTRUDA® (pembrolizumab) in Combination with Chemotherapy for First-Line Treatment of Non-Small Cell Lung Cancer Demonstrate Response Rates Ranging from 48 to 71 Percent

Excerpt:

“Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced findings from an initial proof-of-concept study of KEYTRUDA®(pembrolizumab), the company’s anti-PD-1 therapy, combined with standard treatments, one with bevacizumab and others without, in non-small cell lung cancer (NSCLC) including chemotherapy in previously untreated patients with NSCLC; the study showed overall response rates (ORR) ranging from 48 to 71 percent, depending on the therapy used. These data, from the phase 1/2 KEYNOTE-021 trial, will be presented today at the 52nd Annual Meeting of the American Society of Clinical Oncology (ASCO) by Dr. Shirish Gadgeel of the Barbara Ann Karmanos Cancer Institute (Abstract #9016) from 8:00 – 11:30 a.m. CDT (Location: Hall A) and in a poster discussion from 3:00 – 4:15 p.m. CDT (Location: E354b).

“ ‘Combining KEYTRUDA and chemotherapy in the first-line lung cancer treatment setting is an important part of our effort to develop more treatment options for patients with non-small cell lung cancer,’ said Dr. Roger Dansey, senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. ‘This study has helped us to identify chemotherapy options for combination with KEYTRUDA regardless of PD-L1 expression to take forward in phase 3 trials.’ ”

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Afatinib a Better Choice for EGFR-Mutated Lung Cancer in First-Line Treatment

“Patients with EGFR-activating mutations in advanced lung cancer seem to benefit more from afatinib than gefitinib as first-line treatment, researchers report at the first ESMO Asia 2015 Congress in Singapore.

“In the global, randomised, open-label Phase IIb LUX-Lung 7 (LL7) trial, the irreversible ErbB family blocker afatinib significantly improved efficacy versus gefitinib across a range of clinically relevant endpoints, such as progression-free survival, time-to- failure and objective response rate. ‘Based on these results I would consider afatinib as the EGFR (TKI) of choice for the first-line treatment for patients with EGFR mutation-positive non-small-cell (NSCLC),’ lead author, Professor Keunchil Park, head of the Division of Hematology/Oncology at Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, said.”


Durvalumab/Tremelimumab Combo Could Be Useful in First-Line Treatment for NSCLC

“A combination of the anti–PD-L1 immune checkpoint inhibitor durvalumab (MEDI4736) with the anti–CTLA-4 monoclonal antibody tremelimumab showed improved tumor response in patients with advanced non–small cell lung cancer (NSCLC) over single-agent therapy.

“The study, published in the Journal for ImmunoTherapy of Cancer, was a phase I, open-label, dose-escalation/expansion study that contained 84 patients. Of these patients, 48 had two or more prior lines of therapy. Data from the study showed improved tumor response regardless of PD-L1 status, with an overall response rate of 25% and 35% of PD-L1-negative patients receiving a response (0% tumor cell staining).”


Nivolumab and Ipilimumab Combination Active as First-Line Therapy for Advanced NSCLC

“Nivolumab (Opdivo) and ipilimumab (Yervoy), a chemotherapy-free regimen, showed activity as a first-line therapy for patients who have advanced non-small cell lung cancer (NSCLC), according to a preliminary clinical trial that was presented at this year’s World Conference on Lung Cancer.

“Four different regimens of nivolumab, the PD-1 inhibitor, and ipilimumab, the anti-CTLA-4 antibody, led to response rates of 13% to 39% in 148 patients with no prior exposure to systemic therapy. The combination produced deep and durable responses, with a low rate of treatment-emergent grade 3/4 adverse events (AEs) leading to discontinuation.

“ ‘Clinical activity was observed regardless of tumor PD-L1 expression,’ said lead investigator Naiyer A. Rizvi, MD, director of Thoracic Oncology and Immunotherapeutics at Columbia University Medical Center. ‘We have preliminary evidence of greater activity in tumors that have 1% or greater PD-L1 expression. The median disease control rate [response plus stable disease] was not reached in any arm, regardless of PD-L1 expression.’ “


ABRAXANE® Approved by European Commission for First-Line Treatment of Patients with Non-Small Cell Lung Cancer

“Celgene International Sàrl, a wholly owned subsidiary of Celgene Corporation CELG, -0.88% today announced that the European Commission (EC) has approved ABRAXANE® (paclitaxel formulated as albumin-bound nanoparticles, or nab-paclitaxel) in combination with carboplatin for the first-line treatment of non-small cell lung cancer in adult patients who are not candidates for potentially curative surgery and/or radiation therapy.

“The ABRAXANE Marketing Authorisation has been updated across 28 member states in the European Union to include this new indication in non-small cell lung cancer (NSCLC), adding to the existing indications for the treatment of metastatic pancreatic and breast cancers.

“Lung cancer is the fourth most commonly diagnosed cancer in both men and women, however it is the leading cause of cancer-related mortality in Europe. Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for 85 to 90% of all cases. The predominant cause of lung cancer is cigarette smoking, although environmental and occupational factors also can cause the cancer.

“The EC decision follows the positive CHMP opinion received on 23 January and is based on the results of a multicenter, randomized, open-label study including 1,052 chemotherapy-naive patients with Stage IIIb/IV non-small cell lung cancer. The study compared ABRAXANE in combination with carboplatin versus solvent-based paclitaxel in combination with carboplatin as first-line treatment in patients with advanced non-small cell lung cancer. The primary efficacy endpoint, overall response rate, was significantly higher for patients in the ABRAXANE/carboplatin arm at 33%, compared with patients in the control arm, at 25%. The most common adverse reactions (greater-than or equal to 20%) of ABRAXANE in combination with carboplatin for NSCLC were anaemia, neutropenia, thrombocytopenia, peripheral neuropathy, nausea, and fatigue.”


Adding Palbociclib to Letrozole Treatment Delays Cancer Worsening in Postmenopausal Women with Advanced ER+ HER2- Breast Cancer

The gist: Adding the drug palbociclib to letrozole treatment might help delay cancer getting worse in postmenopausal women with advanced, ER-positive, HER2-negative breast cancer. That was the conclusion of a recent clinical trial that tested the drug combo in volunteer patients. The trial specifically tested the palbociclib/letrozole combo as a “first-line” treatment, meaning the first drugs given to a patient to treat their advanced cancer.

“In the phase II PALOMA-1/TRIO-18 trial reported in The Lancet Oncology, Finn et al found that the addition of palbociclib to letrozole resulted in significant improvement in progression-free survival as first-line treatment for advanced disease in postmenopausal women with estrogen receptor–positive/HER2-negative breast cancer. Palbociclib is an oral small-molecule inhibitor of cyclin-dependent kinases 4 and 6.

“In the open-label study, patients were enrolled in two sequential cohorts, one including patients on the basis of estrogen receptor–positive/HER2-negaitve status alone (cohort 1) and another that required presence of amplification of cyclin D1 (CCND1), loss of p16 (INK4A or CDKN2A), or both (cohort 2). In both cohorts, patients were randomly assigned between December 2009 and May 2012 to receive continuous letrozole at 2.5 mg daily with or without palbociclib at 125 mg once daily for 3 weeks followed by 1 week off in 28-day cycles…

“The investigators concluded: ‘The addition of palbociclib to letrozole in this phase 2 study significantly improved progression-free survival in women with advanced oestrogen receptor-positive and HER2-negative breast cancer. A phase 3 trial is currently underway.’ “


Treatment with Fulvestrant Improved Survival Over Anastrozole in Untreated, Advanced, HR+ Breast Cancer

The gist: A clinical trial with volunteer patients found that a drug called fulvestrant outperformed the drug anastrozole for women with advanced, hormone receptor-positive breast cancer. None of the women had received any other treatment for their cancer. “Patients assigned fulvestrant survived a median of 54.1 months compared with 48.4 months for anastrozole.”

“Fulvestrant 500 mg significantly improved overall survival compared with anastrozole, among women with treatment-naive, advanced, hormone receptor-positive breast cancer, according to data from the phase II FIRST trial presented at the 2014 San Antonio Breast Cancer Symposium (SABCS).

“ ‘This is now the second randomized controlled trial where fulvestrant 500 mg has shown a time-to-progression and survival advantage over the control arm,” said study presenter John Robertson, MD, professor of surgery, University of Nottingham, Royal Derby Hospital, United Kingdom.

“The phase III CONFIRM study found fulvestrant 500 mg to have a survival advantage over anastrozole in the second-line setting.

“According to Robertson, fulvestrant was originally developed in a 250 mg dosage. However, early trials of fulvestrant 250 mg in the first and second line showed only equivalence to anastrozole and similarity to tamoxifen. However, when it was decided to double the dose, and the CONFIRM study showed a survival advantage for fulvestrant 500 mg, the researchers decided to also look at outcomes with the higher dose in the first-line setting.”


Pfizer's Xalkori Shows First-Line Benefit in ALK-Positive NSCLC

The gist: The drug Xalkori (aka crizotinib) has shown promise for treating people with a certain type of non-small cell lung cancer (NSCLC) who have not yet taken any other treatment. A clinical trial tested Xalkori in untreated NSCLC patients whose tumors had mutations of the ALK gene (“ALK-positive”). People who took Xalkori in the trial had almost 4 more months before their cancer worsened than people who took only chemotherapy.

“Pfizer’s targeted cancer therapy Xalkori (crizotinib) significantly extended progression-free survival in previously-untreated patients with a particular form of non-small cell lung cancer taking part in a late-stage trial compared to chemotherapy alone.

“Data from the Phase III PROFILE 1014 study, published in The New England Journal of Medicine, showed that patients with ALK-positive advanced NSCLC given Pfizer’s kinase inhibitor had a median PFS of 10.9 months compared to 7 months for those in the chemotherapy arm. Also, the objective response rate was much higher at 74% versus 45%, the firm noted.

“On the safety side, no unexpected issues arose in the trial, with the most commonly reported adverse events observed in the Xalkori being vision disorder (71%), diarrohea (61%), nausea (56%) and oedema (49%), and with chemotherapy, nausea (59%), fatigue (38%), vomiting (36%) and decreased appetite (34%).

“ALK gene rearrangements are present in about 5% of NSCLC cancers typically occurring in younger patients who don’t smoke. By identifying and enrolling only those patients whose advanced NSCLC tumours are ALK-positive, “this trial was able to demonstrate the superiority of Xalkori over an intravenous platinum-based chemotherapy regimen that has been a standard first-line treatment for more than a decade,” said Mace Rothenberg, chief medical officer for Pfizer Oncology.”