A randomized, phase II study of afatinib versus cetuximab in metastatic or recurrent squamous cell carcinoma of the head and neck.

BackgroundAfatinib is an oral, irreversible ErbB family blocker that has shown activity in epidermal growth factor receptor (EGFR)-mutated lung cancer. We hypothesized that the agent would have greater antitumor activity compared with cetuximab in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients, whose disease has progressed after platinum-containing therapy.Patients and methodsAn open-label, randomized, phase II trial was conducted in 43 centers; 124 patients were randomized (1 : 1) to either afatinib (50 mg/day) or cetuximab (250 mg/m(2)/week) until disease progression or intolerable adverse events (AEs) (stage I), with optional crossover (stage II). The primary end point was tumor shrinkage before crossover assessed by investigator (IR) and independent central review (ICR).ResultsA total of 121 patients were treated (61 afatinib, 60 cetuximab) and 68 crossed over to stage II (32 and 36 respectively). In stage I, mean tumor shrinkage by IR/ICR was 10.4%/16.6% with afatinib and 5.4%/10.1% with cetuximab (P = 0.46/0.30). Objective response rate was 16.1%/8.1% with afatinib and 6.5%/9.7% with cetuximab (IR/ICR). Comparable disease control rates were observed with afatinib (50%) and cetuximab (56.5%) by IR; similar results were seen by ICR. Most common grade ≥3 drug-related AEs (DRAEs) were rash/acne (18% versus 8.3%), diarrhea (14.8% versus 0%), and stomatitis/mucositis (11.5% versus 0%) with afatinib and cetuximab, respectively. Patients with DRAEs leading to treatment discontinuation were 23% with afatinib and 5% with cetuximab. In stage II, disease control rate (IR/ICR) was 38.9%/33.3% with afatinib and 18.8%/18.8% with cetuximab.ConclusionAfatinib showed antitumor activity comparable to cetuximab in R/M HNSCC in this exploratory phase II trial, although more patients on afatinib discontinued treatment due to AEs. Sequential EGFR/ErbB treatment with afatinib and cetuximab provided sustained clinical benefit in patients after crossover, suggesting a lack of cross-resistance

Extensive limb-sparing surgery with reconstruction for sarcoma of the hand and wrist

International audienceBACKGROUND:Sarcoma rarely involves the hand or wrist. Extensive surgical excision is the current standard of care. At the extremities, such as the hand and wrist, limb-sparing surgery with reconstruction to provide optimal function is increasingly performed. A descriptive case-series study of 16 patients with sarcoma of the hand and wrist managed using limb-sparing surgery is reported here.MATERIAL AND METHODS:Of 19 patients with sarcoma of the hand or wrist treated between 1999 and 2012, 16 were managed using limb-sparing surgery. These were consecutive patients managed at a single-centre and studied retrospectively. The tumour involved the hand in 7 patients and the wrist in 9 patients. The procedure was primary in 6 patients, whereas 10 patients underwent secondary revision surgery. In 12 patients, reconstruction was performed for one or more of the following structures: nerves (n=2), tendons (n=3), bone (n=3), and/or skin (n=8). After surgical excision, the margins were R0 in 15 patients and R1 in 1 patient. At last follow-up, survival, pain, and function as reflected by the DASH and MSTS scores were assessed.RESULTS:After the median follow-up of 4.5years [1-13], 15 patients were alive with no local recurrence and 1 patient had lung metastases. Mean values were 18 [0-49] for the DASH score and 88.8% [53-100] for the MSTS score.DISCUSSION:Limb-sparing surgery reconciles the need to achieve complete tumour excision with the need to restore function. No limits should be placed on tumour excision, given the availability of effective reconstructive methods. The functional outcome depends on the tolerance of adjuvant treatments, most notably radiotherapy.LEVEL OF EVIDENCE:IV, retrospective study

A randomized, phase II study of afatinib versus cetuximab in metastatic or recurrent squamous cell carcinoma of the head and neck

Afatinib is an oral, irreversible ErbB family blocker that has shown activity in epidermal growth factor receptor (EGFR)-mutated lung cancer. We hypothesized that the agent would have greater antitumor activity compared with cetuximab in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients, whose disease has progressed after platinum-containing therapy.status: publishe